Durvalumab, a recombinant fully human anti-programmed-death ligand-1 (anti-PD-L1) monoclonal antibody, is an antineoplastic agent.1 The drug is an IgG1 kappa immunoglobulin.1
Durvalumab is used in combination with platinum-containing chemotherapy as neoadjuvant treatment, followed by durvalumab continued as a single agent as adjuvant treatment after surgery, for the treatment of resectable (tumors ≥4 cm and/or node positive) non-small cell lung cancer (NSCLC) with no known epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) rearrangements in adults.1
Durvalumab is also used for the treatment of unresectable stage III NSCLC that has not progressed following platinum-based chemotherapy combined with radiation therapy in adults.1, 11, 12
Durvalumab is also used in combination with tremelimumab-actl and platinum-based chemotherapy for the treatment of metastatic NSCLC with no sensitizing EGFR mutations or ALK genomic tumor aberrations in adults.1
Neoadjuvant and Adjuvant Treatment of Resectable Non-small Cell Lung Cancer
The current indication for the use of durvalumab in combination with platinum-containing chemotherapy as neoadjuvant treatment, followed by continued use of durvalumab as a single-agent as adjuvant treatment after surgery, for the treatment of adults with resectable NSCLC is based principally on the results of a double-blind, randomized, placebo-controlled, phase 3 study (AEGEAN).1, 14 Patients with newly diagnosed, previously untreated, resectable NSCLC, regardless of tumor programmed death-ligand 1 (PD-L1) expression, were enrolled.1, 14 There were 802 patients randomized (stratified by stage and level of PD-L1 expression) in a 1:1 ratio to receive a neoadjuvant-adjuvant durvalumab regimen or placebo regimen.1, 14 Those randomized to the durvalumab regimen received neoadjuvant durvalumab (1500 mg by IV infusion) once every 3 weeks for up to 4 cycles in combination with platinum-based chemotherapy.1, 14 Platinum-based regimens for NSCLC of squamous tumor histology consisted of either carboplatin (AUC 6) and paclitaxel (200 mg/m2) on day 1 of each 3-week cycle, or cisplatin (75 mg/m2) on day 1 and gemcitabine (1250 mg/m2) on day 1 and day 8 of each 3-week cycle, for 4 cycles.1 Platinum-based regimens for NSCLC of non-squamous tumor histology consisted of pemetrexed (500 mg/m2) and cisplatin (75 mg/m2) on day 1 of each 3-week cycle, or pemetrexed (500 mg/m2) and carboplatin (AUC 5) on day 1 of each 3-week cycle, for 4 cycles.1 Patients continued to receive IV durvalumab or placebo every 4 weeks for up to 12 cycles after surgery.14
The patients enrolled in AEGEAN were 65 years of age (median); 72% of patients were male, 54% were white, 41% were Asian, 0.9% were Black, 1.4% were American Indian or Alaska Native; 16% were Hispanic or Latino; 49% had squamous histology; 28% had Stage II disease and 71% had Stage III; 86% were current or past smokers; and 33% had PD-L1 expression <1%.1, 14 All patients enrolled had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.1, 14 There were 77.6% of patients in the durvalumab group who completed surgery compared with 76.7% of patients in the placebo group.14 The main efficacy endpoints were pathological complete response and event-free survival.1, 14
At a pre-planned interim analysis of the AEGEAN study (46.3 months after study initiation), there were substantial improvements in pathological complete response and event-free survival in patients who received the durvalumab-containing regimen compared with those receiving placebo.1, 14 The median event-free survival had not been reached for the durvalumab with chemotherapy regimen and was 25.9 months for the placebo with chemotherapy regimen.1, 14 The pathological complete response rate was 17.2% for the durvalumab with chemotherapy regimen compared with 4.3% for the placebo with chemotherapy regimen.1, 14
Unresectable Non-small Cell Lung Cancer
The current indication for durvalumab in the treatment of unresectable NSCLC that has not progressed following platinum-based chemotherapy combined with radiation therapy is based principally on the results of a multicenter, double-blind, randomized, placebo-controlled, phase 3 trial (PACIFIC).1, 11, 12 In this study, 713 patients with unresectable stage III NSCLC that had not progressed following at least 2 cycles of platinum-based chemotherapy and concurrent radiation therapy within 42 days of study initiation, were randomized (stratified by gender, age, and smoking history) in a 2:1 ratio to receive either durvalumab (10 mg/kg by IV infusion every 2 weeks) or placebo.1, 11, 12 Treatment was continued for up to 12 months or until disease progression or unacceptable toxicity occurred.1, 11, 12 The median age of patients in this study was 64 years; 69% of patients were white; 27% were Asian; 70% were male; 75% were former smokers and 16% were current smokers; and 51% had a baseline ECOG performance status of 1.1 All patients had received radiation therapy and 99% of patients had received concomitant platinum-based chemotherapy; 55 or 42% of patients had received prior treatment with cisplatin- or carboplatin-based regimens, respectively, and 2% switched between cisplatin and carboplatin.1 This study excluded patients whose disease progressed during platinum-containing chemotherapy and radiation therapy, those with autoimmune disease within the previous 2 years, and those receiving immunosuppressive agents.1 The primary measures of efficacy were progression-free survival and overall survival (as evaluated by a blinded independent central review committee according to RECIST); an additional outcome measure was overall response rate.1, 11
In the PACIFIC study, patients receiving durvalumab had a longer median progression-free survival compared with patients receiving placebo (16.8 months versus 5.6 months).1, 11 Median overall survival had not been reached at the time of the interim analysis (at a median follow-up of 14.5 months).11 At the time of the interim analysis, patients receiving durvalumab had higher overall response rates compared with those receiving placebo (26 versus 14%); complete responses were achieved in 1 or 0% of patients receiving durvalumab or placebo, respectively.1
At a pre-planned interim overall survival analysis of the PACIFIC study at a median follow-up of 25.2 months, patients receiving durvalumab had a longer median overall survival compared with patients receiving placebo (median not reached versus 28.7 months, respectively).1, 12 A 5-year survival outcomes study of PACIFIC reported outcomes at a median duration of follow-up of 34.2 months for all randomly assigned patients in PACIFIC and 61.6 months for censored patients (defined as patients last known to be alive).15 The median overall survival for patients in the durvalumab group was 47.5 months versus 29.1 months for patients in the placebo group.15 The 5-year overall survival rate was estimated to be 42.9 and 33.4% for the durvalumab and placebo groups, respectively.15
Metastatic Non-small Cell Lung Cancer
The current indication for durvalumab, in combination with tremelimumab and platinum-based chemotherapy, for the treatment of metastatic NSCLC without EGFR or ALK genomic aberrations in adults is based principally on the results of a randomized, open-label, active-controlled, phase 3 study (POSEIDON).1, 16 In this study, 1013 adults with previously untreated metastatic NSCLC were randomized (stratified by PD-L1 expression, disease stage, and histology) 1:1:1 to receive tremelimumab plus durvalumab and chemotherapy, durvalumab plus chemotherapy, or chemotherapy alone.1, 16 Those randomized to the tremelimumab plus durvalumab group received tremelimumab 75 mg (or 1 mg/kg for patients <30 kg) with durvalumab 1500 mg and platinum-based chemotherapy every 3 weeks for 4 cycles, followed by durvalumab 1500 mg every 4 weeks until disease progression.1, 16 There was a fifth dose of tremelimumab given at week 16 in combination with durvalumab dose 6.1, 16 Patients in the durvalumab plus chemotherapy group received durvalumab 1500 mg plus chemotherapy for up to 4 cycles of 21 days each, followed by durvalumab 1500 mg once every 4 weeks until disease progression.16 Patients in the chemotherapy group received therapy for up to 6 cycles that were 21 days each.16 Chemotherapy regimen options included one of the following: nab-paclitaxel (100 mg/m2) on days 1, 8, and 15 with carboplatin (AUC 5-6) on day 1 every 3 weeks for any histology; pemetrexed (500 mg/m2) with carboplatin (AUC 5-6) or cisplatin (75 mg/m2) every 3 weeks for non-squamous NSCLC; or gemcitabine (1000 or 1250 mg/m2) on days 1 and 8 with cisplatin (75 mg/m2) or carboplatin (AUC 5-6) on day 1 every 3 weeks for squamous NSCLC.1, 16
The patients in the POSEIDON trial were 63 years of age (median); 77% of patients were male, 57% were white, 34% were Asian, 3% were American Indian or Alaska Native, 2% were Black, 0.3% were Native Hawaiian or Other Pacific Islander; 79% were former or current smokers; 63% had non-squamous histology; and 71% had a PD-L1 expression tumor proportion score of less than 50%.1 All patients had an ECOG performance status of 0 or 1.1 The main efficacy measures were progression-free survival and overall survival.1, 16 The median follow-up for censored patients was 10.3 months and 34.9 months for progression-free survival and overall survival, respectively.16
In the POSEIDON trial, durvalumab, in combination with tremelimumab and platinum-based chemotherapy, substantially improved overall survival and progression-free survival.1, 16 The median progression-free survival was 6.2 months for patients in the durvalumab plus tremelimumab and chemotherapy group and 4.8 months for the chemotherapy alone group.16 The median overall survival was 14 months and 11.7 months for the durvalumab plus tremelimumab and chemotherapy group and chemotherapy alone group, respectively.1, 16 Results of a subgroup analysis (based on age and tumor PD-L1 expression) were generally consistent.16 The progression-free survival and overall survival benefits appeared more prominent in non-squamous (versus squamous) NSCLC histology.16
Guidelines for NSCLC have been published by the American Society of Clinical Oncology (ASCO), including for stage III and stage IV NSCLC.17, 18 For patients with stage III NSCLC receiving concurrent chemoradiation without disease progression during initial therapy, the ASCO guideline states that consolidation with durvalumab for up to 12 months should be offered.17 The living guideline by ASCO for the treatment of patients with stage IV NSCLC without driver mutations states that clinicians may offer durvalumab and tremelimumab plus platinum-based chemotherapy as a first-line treatment option for stage IV patients with good performance status.18
Durvalumab is used as a single agent for the treatment of limited-stage small cell lung cancer (SCLC) that has not progressed following concurrent platinum-based chemotherapy and radiation therapy in adults.1 Durvalumab has been designated an orphan drug by FDA for the treatment of this type of SCLC.4
Durvalumab is also used in combination with etoposide and either carboplatin or cisplatin as first-line treatment for extensive-stage SCLC in adults.1 Durvalumab has been designated an orphan drug by FDA for the treatment of this type of SCLC.4
Limited-stage Small Cell Lung Cancer
The current indication for durvalumab as a single agent for the treatment of limited-stage SCLC that has not progressed following concurrent platinum-based chemotherapy and radiation is based principally on the results of a randomized, double-blind, placebo-controlled study (ADRIATIC).1, 19 In this study, 730 adults with histologically or cytologically confirmed limited-stage SCLC whose disease had not progressed following concurrent chemoradiation therapy were randomized (stratified by stage [I/II versus III]) and receipt of prophylactic cranial irradiation) 1:1:1 to receive durvalumab, durvalumab plus tremelimumab, or placebo.1, 19 Those randomized to the tremelimumab group received tremelimumab (75 mg) with durvalumab (1500 mg) every 4 weeks for 4 cycles followed by durvalumab (1500 mg) every 4 weeks until disease progression, unacceptable toxicity, or up to a maximum of 24 months.1, 19 Those in the durvalumab group received durvalumab (1500 mg) in combination with tremelimumab-matched placebo every 4 weeks for 4 cycles, followed by durvalumab (1500 mg) every 4 weeks.1, 19 Those in the placebo group received durvalumab and tremelimumab-matched placebos every 4 weeks for 4 cycles, followed by the durvalumab-matched placebo every 4 weeks thereafter.1, 19
The patients in the ADRIATIC trial were 62 years of age (median).19 There were 69% of patients who were male; 50% were white, 0.8% were Black, 48% were Asian, 4.2% were Hispanic or Latino, 22% were current smokers, and 68% were past smokers.1 There were 87.4% of patients with stage III disease at diagnosis; previous concurrent chemotherapy included regimens with cisplatin plus etoposide (66.2%) and carboplatin plus etoposide (33.8%).1, 19 All patients had an ECOG performance status of 0 or 1.1 The main efficacy measures were overall survival and progression-free survival.1, 19 For censored patients, the median follow-up for overall survival was 37.2 months for both the durvalumab and placebo group; the median follow-up for progression-free survival was 27.4 months and 27.7 months for the durvalumab group and placebo group, respectively.19
In the ADRIATIC trial, durvalumab substantially improved overall survival and progression-free survival.1, 19 The median progression-free survival was 16.6 months for patients in the durvalumab group and 9.2 months for the placebo group.19 The median overall survival was 55.9 months and 33.4 months for the durvalumab and placebo groups, respectively.1, 19
Extensive-stage Small Cell Lung Cancer
The current indication for durvalumab in combination with etoposide and either carboplatin or cisplatin as first-line treatment for extensive-stage SCLC in adults is based principally on the results of a randomized, open-label, active-controlled, phase 3 study (CASPIAN).1, 20 In this study, 805 adults with treatment-naïve histologically or cytologically documented extensive-stage SCLC were randomized (stratified according to planned platinum therapy) in a 1:1:1 ratio to receive durvalumab plus platinum-etoposide, durvalumab plus tremelimumab plus platinum-etoposide, or platinum-etoposide alone.20 Those randomized to the tremelimumab plus durvalumab group receive IV tremelimumab (75 mg) with durvalumab (1500 mg) and platinum-based chemotherapy every 3 weeks for 4 cycles, followed by durvalumab (1500 mg) every 4 weeks until disease progression or unacceptable toxicity.20 Patients in the durvalumab group received durvalumab (1500 mg) with platinum-based chemotherapy every 3 weeks for 4 cycles, followed by durvalumab (1500 mg) every 4 weeks.20 Patients in the chemotherapy alone group received therapy for up to 6 cycles total and prophylactic cranial irradiation after chemotherapy based on the investigator's discretion.20 The chemotherapy regimen for all groups consisted of the investigator's choice of either carboplatin (AUC 5 or 6) or cisplatin (75—80 mg/m2) on Day 1 and etoposide (80—1000 mg/m2) IV on days 1, 2, and 3 of each 21-day cycle.1 Continuation of durvalumab as a single agent was permitted beyond disease progression if the patient was deriving clinical benefit and was clinically stable.1, 20
The patients in the CASPIAN trial were 63 years of age (median); 70% were male, 84% were white, 15% were Asian, 0.9% were Black; and 93% were former or current smokers.1, 20 There were 90% of patients that had stage IV disease, and 10% had brain metastasis at baseline.1, 20 All patients had an ECOG performance status of 0 or 1.1, 20 Within the study, 25% of patients received cisplatin, and 74% received carboplatin.1 The main efficacy measure was overall survival of durvalumab plus chemotherapy versus chemotherapy alone.1, 20 Additional efficacy measures were progression-free survival and objective response rate.1 The median follow-up for censored patients for overall survival was 14.2 months.20
In the CASPIAN trial, durvalumab, in combination with platinum-based chemotherapy versus chemotherapy alone, substantially improved overall survival.1, 20 The median overall survival was 13 and 10.3 months for the durvalumab plus chemotherapy group and chemotherapy alone group, respectively.1, 20 The median progression-free survival was 5.1 months for patients in the durvalumab plus chemotherapy group and 5.4 months for the chemotherapy alone group.1, 20 The investigators-assessed confirmed objective response rate was higher with durvalumab plus chemotherapy (68%) compared with chemotherapy alone (58%).1, 20 Results of a subgroup analysis (based on baseline clinical and demographic characteristics) found a consistent overall survival benefit with durvalumab plus chemotherapy.20 An updated analysis of the CASPIAN trial at a median follow-up of 25.1 months was conducted and found sustained benefit in overall survival with durvalumab plus chemotherapy (median, 12.9 months) compared with chemotherapy alone (median, 10.5 months).21
Guidelines for SCLC have been published by ASCO and Ontario Health (Cancer Care Ontario).22, 23 For patients with extensive-stage SCLC, the ASCO/Ontario Health guideline states first-line systemic therapy with cisplatin or carboplatin plus etoposide plus immunotherapy (e.g., atezolizumab or durvalumab) followed by maintenance immunotherapy should be offered if there are no contraindications to immunotherapy.22 An ASCO guideline rapid recommendation update states that patients with limited-stage SCLC who have completed concurrent chemoradiotherapy and do not have disease progression should be offered consolidation immunotherapy (i.e., durvalumab) for up to 2 years if there are not any contraindications to immunotherapy.23 In addition, this ASCO guideline update states that for patients with limited stage SCLC and ECOG performance status of 3 or 4 due to SCLC who have been treated with concurrent or sequential chemotherapy and radiotherapy may be offered consolidation immunotherapy (i.e., durvalumab) for up to 2 years if there are no contraindications and there is improvement in performance status.23
Durvalumab is used in combination with gemcitabine and cisplatin for the treatment of locally advanced or metastatic biliary tract cancer in adults.1 Durvalumab has been designated an orphan drug by FDA for the treatment of this type of cancer.4
The current indication for durvalumab in combination with gemcitabine and cisplatin for the treatment of locally advanced or metastatic biliary tract cancer is based principally on the results of a randomized, double-blind, placebo-controlled, phase 3 study (TOPAZ-1).1, 24 In this study, 685 patients with histologically confirmed locally advanced unresectable or metastatic biliary tract cancer who had not previously received systemic therapy were randomized (stratified by disease status [recurrent versus initially unresectable] and primary tumor location [intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, or gallbladder cancer]) in a 1:1 ratio to receive durvalumab plus chemotherapy or placebo plus chemotherapy.1, 24 Patients in the durvalumab plus chemotherapy group received IV durvalumab (1500 mg) on day 1 plus gemcitabine (1000 mg/m2) and cisplatin (25 mg/m2) on days 1 and 8 of each 21-day cycle for up to 8 cycles, followed by durvalumab (1500 mg) every 4 weeks until disease progression or unacceptable toxicity.1, 24 Patients in the placebo plus chemotherapy group received placebo on day 1 of each cycle with the same chemotherapy regimen as the durvalumab group for up to 8 cycles, followed by placebo every 4 weeks.1, 24 Treatment after disease progression was allowed if the patient was clinically stable and deriving clinical benefit.1
The patients enrolled in the TOPAZ-1 study were 64 years of age (median); 50% of patients were male, 37% were white, 56% were Asian, 2% were Black, 0.1% were American Indian or Alaskan Native; 20% of patients had recurrent disease; and 86% had metastatic and 14% had locally advanced disease.1 The main efficacy endpoint was overall survival.1, 24 Additional efficacy endpoints included progression-free survival and overall response rate.1, 24 The median duration of follow-up was 16.8 months for patients in the durvalumab group and 15.9 months for patients in the placebo group.24
In the TOPAZ-1 study, median overall survival and progression-free survival was substantially prolonged for patients in the durvalumab plus chemotherapy group compared with patients in the chemotherapy alone group.1, 24 The median overall survival for the durvalumab plus chemotherapy group was 12.8 months versus 11.5 months in the placebo plus chemotherapy group.1, 24 The median progression-free survival was 7.2 months and 5.7 months for the durvalumab plus chemotherapy and placebo plus chemotherapy groups, respectively.1, 24 Objective response rates were 26.7% for patients treated with durvalumab plus chemotherapy and 18.7% for patients treated with placebo plus chemotherapy.1, 24 Results for overall and progression-free survival were generally consistent across the subgroups analyzed.24 An updated analysis of the TOPAZ-1 study was conducted at a median follow-up of 23.4 months in the durvalumab plus chemotherapy group and 22.4 months in the placebo plus chemotherapy group.25 The median overall survival at this cutoff was 12.9 months and 11.3 months for the durvalumab and placebo groups, respectively.25
Recommendations for the treatment of advanced and metastatic disease are available from international experts.26, 27 For advanced or metastatic biliary tract cancer, cisplatin-gemcitabine combined with either durvalumab or pembrolizumab is a viable first-line treatment option.27
Durvalumab is used in combination with tremelimumab-actl for the treatment of unresectable hepatocellular carcinoma in adults.1 Durvalumab has been designated an orphan drug by FDA for the treatment of this type of cancer.4
The current indication for durvalumab in combination with tremelimumab for the treatment of unresectable hepatocellular carcinoma is based principally on the results of a randomized, open-label, phase 3 study (HIMALAYA).1, 28 The HIMALAYA study enrolled 1171 adults with Barcelona Clinic Liver Cancer (BCLC) stage B or C hepatocellular carcinoma and Child-Pugh class A liver function who were previously untreated with prior systemic therapy.1, 28 Patients enrolled were randomized (stratified according to presence of macrovascular invasion, etiology of liver disease, and ECOG performance status) 1:1:1 to receive durvalumab, durvalumab plus tremelimumab, or sorafenib.1, 28 Patients in the durvalumab plus tremelimumab group received durvalumab (1500 mg) with tremelimumab (as a one-time single IV infusion of 300 mg on the same day), followed by durvalumab every 4 weeks.1, 28 Patients in the durvalumab group received durvalumab (1500 mg) every 4 weeks; patients in the sorafenib group received oral sorafenib (400 mg) twice daily.1, 28 Treatment was continued until disease progression or unacceptable toxicity.1, 28 Treatment was also permitted beyond disease progression if the patient was deriving clinical benefit and was clinically stable.1, 28
The patients in the HIMALAYA study were 65 years of age (median); 85% of patients were male; 46% were white; 49% were Asian; 2% were Black, 5% were Hispanic or Latino; 26% had macrovascular invasion, and 53% had extrahepatic spread.1 In terms of viral etiology, 31% had hepatitis B, 27% had hepatitis C, and 42% were uninfected.1 The main measure of efficacy was overall survival; progression-free survival and overall response rate were additional efficacy measures.1, 28 The median follow-up for this study was 33.2 months for durvalumab plus tremelimumab, 32.6 months for durvalumab, and 32.2 months for sorafenib.28
In HIMALAYA, durvalumab plus tremelimumab substantially improved overall survival compared to placebo in patients with unresectable hepatocellular carcinoma.1, 28 Median overall survival was 16.4 for the durvalumab plus tremelimumab group and 13.8 months for the placebo group.1, 28 Median progression-free survival was 3.8 months for the durvalumab plus tremelimumab group and 4.1 months for the placebo group.1, 28 Confirmed objective response rates were 20.1 and 5.1% with durvalumab plus tremelimumab and sorafenib groups, respectively.1, 28 A 4-year overall survival analysis of the HIMALAYA study was also conducted.29 For this analysis, the median follow-up was 49.1 months for the durvalumab plus tremelimumab group and 47.3 months for the sorafenib group.29 The median overall survival at this time point was 16.4 months and 13.8 months for the durvalumab plus tremelimumab and sorafenib groups, respectively.29
Guidelines for systemic therapy for advanced hepatocellular carcinoma have been published by ASCO.30 For first-line treatment of advanced hepatocellular carcinoma in patients with Child-Pugh class A liver disease and ECOG performance status of 0 or 1, atezolizumab plus bevacizumab or durvalumab plus tremelimumab may be offered.30 Sorafenib, lenvatinib, or durvalumab may also be offered as first-line treatment for these patients when there are contraindications to atezolizumab plus bevacizumab or durvalumab plus tremelimumab.30 If sorafenib or lenvatinib were used first-line, another tyrosine kinase inhibitor (TKI), ramucirumab, nivolumab plus ipilimumab, or durvalumab may be recommended for appropriate patients.30
A guideline on the treatment of hepatocellular carcinoma from the American Association for the Study of Liver Diseases (AASLD) provides similar recommendations, stating that atezolizumab plus bevacizumab or durvalumab plus tremelimumab are first-line therapies for advanced hepatocellular carcinoma in patients with Child-Pugh class A liver disease.33 In patients with contraindications to these therapies, the AASLD recommends sorafenib or lenvatinib for first-line systemic treatment.33
Durvalumab is used in combination with carboplatin and paclitaxel, followed by durvalumab as a single agent, for the treatment of primary advanced or recurrent endometrial cancer that is mismatch repair deficient, as determined by an FDA-approved test, in adults.1
The current indication for durvalumab in combination with carboplatin and paclitaxel, followed by durvalumab as a single agent, for the treatment of primary advanced or recurrent endometrial cancer is based primarily on the results of a randomized, double-blind, placebo-controlled, phase 3 study (DUO-E).1, 31 There were 718 patients with newly diagnosed advanced or recurrent endometrial cancer that were randomized (stratified by tumor mismatch repair status [proficient or deficient], disease status [recurrent or newly diagnosed], and geographic region) 1:1:1 to receive durvalumab in combination with carboplatin and paclitaxel, placebo in combination with carboplatin and paclitaxel, or durvalumab plus olaparib in combination with carboplatin and paclitaxel.1, 31 The chemotherapy regimen consisted of the following for all patients: carboplatin (AUC 5 or 6) and paclitaxel (175 mg/m2) once every 3 weeks for 6 cycles.1, 31 Patients in the durvalumab plus chemotherapy group also received durvalumab 1120 mg once every 3 weeks for a maximum of 6 cycles, followed by 1500 mg of durvalumab once every 4 weeks as maintenance until disease progression or unacceptable toxicity.1, 31 Patients in the durvalumab plus olaparib and chemotherapy also received the same regimen of durvalumab plus olaparib 300 mg tablets twice daily during the maintenance treatment period.31 Patients in the placebo plus chemotherapy group received matching placebo for durvalumab and olaparib.31
The patients enrolled in DUO-E were 63 years of age (median); 62% of patients were white, 31% were Asian, 2% were Black, 7% were Hispanic or Latino, 1% were America Indian or Alaska Native; 48% were newly diagnosed and 52% had recurrent disease.1 The histologic subtypes were mostly endometrioid (78%), followed by mixed epithelial (6%), carcinosarcoma (5%), and serous (4%).1 There were 80% of patients in the chemotherapy only group and 81% of patients in the durvalumab plus chemotherapy group that had mismatch repair proficient tumors.31 The main efficacy outcome of this trial was progression-free survival.1 For censored patients, the median duration of follow-up was 12.6 months for the chemotherapy only group and 15.4 months for the durvalumab plus chemotherapy group.31 For all tumor types (i.e., mismatch repair proficient and deficient), there was a substantially longer median progression-free survival in the durvalumab plus chemotherapy group (10.2 months) than in the chemotherapy only group (9.6 months).31 In an exploratory analysis based on mismatch repair status, the improvement in progression-free survival was primarily attributed to patients with mismatch repair deficient tumors.1 Within this subgroup of patients, the median progression-free survival had not been reached for the durvalumab plus chemotherapy group compared with a median overall survival of 7 months for the chemotherapy only group.1, 31
The American College of Obstetricians and Gynecologists (ACOG) has published a practice bulletin on the management of endometrial cancer.32 This was published before durvalumab, in combination with carboplatin and paclitaxel, was approved for use in endometrial cancer and therefore does not discuss the use of durvalumab in treatment.32
Administer durvalumab by IV infusion after dilution.1
Administer the diluted durvalumab solution through a sterile, low-protein-binding 0.2- or 0.22-µm inline filter.1
Store durvalumab refrigerated at 2-8°C in the original carton to protect from light.1 Do not freeze or shake.1
Administer diluted solutions of durvalumab immediately after preparation.1 If the diluted solution is not administered immediately, store it for up to 8 hours at room temperature (up to 25°C) or up to 28 days at 2-8°C (total storage time from initial vial entry for preparation of the dilution until start of the IV infusion).1 Do not freeze diluted solutions of the drug.1
Discard any unused portion in the vial or infusion bag since durvalumab injection contains no preservative.1
Do not administer durvalumab simultaneously through the same IV line with any other drug.1
For IV infusion, dilute the appropriate dose of durvalumab injection concentrate (containing 50 mg/mL) with an appropriate volume of 0.9% sodium chloride or 5% dextrose injection to a final concentration between 1-15 mg/mL.1 Prior to administration, visually inspect the solution and container for particulate matter and discoloration.1 The solution should be clear to opalescent and colorless to slightly yellow; do not use the solution if it is cloudy or discolored or if foreign particles are present.1 Mix the diluted solution by gentle inversion and do not shake.1
Administer durvalumab by IV infusion over 60 minutes.1
When used with tremelimumab-actl, infuse tremelimumab-actl first, followed by durvalumab on the same day of dosing.1
When used with tremelimumab-actl and platinum-based chemotherapy, infuse tremelimumab-actl first, followed by durvalumab, and then platinum-based chemotherapy on the same day of dosing.1
When used with tremelimumab-actl and pemetrexed therapy, infuse tremelimumab-actl first, followed by durvalumab, and then pemetrexed therapy on the same day of dosing.1
When used with carboplatin and paclitaxel, infuse durvalumab first and then carboplatin and paclitaxel on the same day of dosing.1
When used with tremelimumab-actl, administer tremelimumab-actl over 60 minutes followed by a 60-minute observation period.1 Then administer durvalumab as a separate IV infusion over 60 minutes.1
When used with tremelimumab-actl and platinum-based chemotherapy/pemetrexed therapy, for cycle 1, administer tremelimumab-actl over 1 hour.1 One to 2 hours after completion of the tremelimumab-actl infusion, administer durvalumab over 1 hour.1 One to 2 hours after completion of the durvalumab infusion, administer platinum-based chemotherapy.1 If there are no infusion reactions during cycle 1, subsequent infusions of durvalumab can be given immediately after tremelimumab-actl.1 The time between the completion of the durvalumab infusion and the start of chemotherapy can be reduced to 30 minutes.1
Resectable Non-small Cell Lung Cancer
Patients Weighing 30 kg : For the neoadjuvant treatment of resectable (tumors ≥4 cm or node positive) non-small cell lung cancer (NSCLC) without known epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) rearrangements, the recommended dosage of durvalumab is 1500 mg in combination with chemotherapy every 3 weeks for up to 4 cycles prior to surgery.1 Therapy should be continued until disease progression that precludes definitive surgery, recurrence, unacceptable toxicity occurs, or a maximum of 12 cycles after surgery.1
For the adjuvant treatment of resectable (tumors ≥4 cm or node positive) NSCLC without known EGFR mutations or ALK rearrangements, the recommended dosage of durvalumab is 1500 mg as a single agent every 4 weeks for up to 12 cycles after surgery.1 Therapy should be continued until disease progression that precludes definitive surgery, recurrence, unacceptable toxicity occurs, or a maximum of 12 cycles after surgery.1
Patients Weighing 30 kg : For the neoadjuvant treatment of resectable (tumors ≥4 cm or node positive) NSCLC without known EGFR mutations or ALK rearrangements, the recommended dosage of durvalumab is 20 mg/kg in combination with chemotherapy every 3 weeks for up to 4 cycles prior to surgery.1 Therapy should be continued until disease progression that precludes definitive surgery, recurrence, unacceptable toxicity occurs, or a maximum of 12 cycles after surgery.1
For the adjuvant treatment of resectable (tumors ≥4 cm or node positive) NSCLC without known EGFR mutations or ALK rearrangements, the recommended dosage of durvalumab is 20 mg/kg as a single agent every 4 weeks for up to 12 cycles after surgery.1 Therapy should be continued until disease progression that precludes definitive surgery, recurrence, unacceptable toxicity occurs, or a maximum of 12 cycles after surgery.1
Unresectable Stage III Non-small Cell Lung Cancer
Patients Weighing 30 kg : For the treatment of unresectable NSCLC that has not progressed following platinum-based chemotherapy combined with radiation therapy, the recommended dosage of durvalumab is 10 mg/kg every 2 weeks or 1500 mg every 4 weeks.1 Therapy should be continued until disease progression or unacceptable toxicity occurs, or for a maximum of 12 months.1
Patients Weighing 30 kg : For the treatment of unresectable NSCLC that has not progressed following platinum-based chemotherapy combined with radiation therapy, the recommended dosage of durvalumab is 10 mg/kg every 2 weeks.1 Therapy should be continued until disease progression or unacceptable toxicity occurs, or for up a maximum of 12 months.1
Metastatic Non-small Cell Lung Cancer
Patients Weighing 30 kg : For the treatment of metastatic, non-squamous NSCLC, the recommended dosage of durvalumab is 1500 mg every 3 weeks for cycles 1—5 and then every 4 weeks for cycle 6—8.1 Patients should receive concomitant treatment with tremelimumab 75 mg at cycles 1, 2, 3, 4 and 6 and a recommended platinum-based chemotherapy regimen for all 8 cycles.1 Therapy should be continued until disease progression or unacceptable toxicity occurs.1
For the treatment of metastatic, squamous NSCLC, the recommended dosage of durvalumab is 1500 mg every 3 weeks for cycles 1—5 and then every 4 weeks for cycles 6—8.1 Patients should receive concomitant treatment with tremelimumab 75 mg at cycles 1, 2, 3, 4 and 6 and a recommended platinum-based chemotherapy regimen for all 8 cycles.1 Therapy should be continued until disease progression or unacceptable toxicity occurs.1
Patients Weighing 30 kg : For the treatment of metastatic, non-squamous NSCLC, the recommended dosage of durvalumab is 20 mg/kg every 3 weeks for cycles 1—5 and then every 4 weeks for cycle 6—8.1 Patients should receive concomitant treatment with tremelimumab 1 mg/kg at cycles 1, 2, 3, 4 and 6 and a recommended platinum-based chemotherapy regimen for all 8 cycles.1 Therapy should be continued until disease progression or unacceptable toxicity occurs.1
For the treatment of metastatic, squamous NSCLC, the recommended dosage of durvalumab is 20 mg/kg every 3 weeks for cycles 1—5 and then every 4 weeks for cycle 6—8.1 Patients should receive concomitant treatment with tremelimumab 1 mg/kg at cycles 1, 2, 3, 4 and 6 and a recommended platinum-based chemotherapy regimen for all 8 cycles.1 Therapy should be continued until disease progression or unacceptable toxicity occurs.1
Limited-stage Small Cell Lung Cancer
Patients Weighing 30 kg : For the treatment of limited-stage small cell lung cancer (LS-SCLC) that has not progressed following concurrent platinum-based chemotherapy and radiation therapy, the recommended dosage of durvalumab is 1500 mg g every 4 weeks.1 Therapy should be continued until disease progression or unacceptable toxicity occurs or for a maximum of 24 months.1
Patients Weighing 30 kg : For the treatment of LS-SCLC that has not progressed following concurrent platinum-based chemotherapy and radiation therapy, the recommended dosage of durvalumab is 20 mg/kg every for 4 weeks.1 Therapy should be continued until disease progression or unacceptable toxicity occurs or for a maximum of 24 months.1
Extensive-stage Small Cell Lung Cancer
Patients Weighing 30 kg : For the treatment of extensive-stage small cell lung cancer (ES-SCLC), the recommended dosage of durvalumab is 1500 mg in combination with chemotherapy every 3 weeks (21 days) for 4 cycles followed by 1500 mg every 4 weeks as a single agent.1 Therapy should be continued until disease progression or unacceptable toxicity occurs.1
Patients Weighing 30 kg : For the treatment of ES-SCLC, the recommended dosage of durvalumab is 20 mg/kg in combination with chemotherapy every 3 weeks (21 days) for 4 cycles, followed by 10 mg/kg every 2 weeks as a single agent.1 Therapy should be continued until disease progression or unacceptable toxicity occurs.1
Patients Weighing 30 kg : For the treatment of locally advanced or metastatic biliary tract cancer (BTC), the recommended dosage of durvalumab is 1500 mg in combination with chemotherapy every 3 weeks (21 days) for up to 8 cycles followed by 1500 mg every 4 weeks as a single agent.1 Therapy should be continued until disease progression or unacceptable toxicity occurs.1
Patients Weighing 30 kg : For the treatment of locally advanced or metastatic BTC, the recommended dosage of durvalumab is 20 mg/kg in combination with chemotherapy every 3 weeks (21 days) for up to 8 cycles, followed by 20 mg/kg every 4 weeks as a single agent.1 Therapy should be continued until disease progression or unacceptable toxicity occurs.1
Unresectable Hepatocellular Carcinoma
Patients Weighing 30 kg : For the treatment of unresectable hepatocellular carcinoma (uHCC), the recommended dosage of durvalumab is 1500 mg following a single dose of tremelimumab-actl 300 mg at day 1 of cycle 1; then, continue durvalumab 1500 mg as a single agent every 4 weeks.1 Therapy should be continued until disease progression or unacceptable toxicity occurs.1
Patients Weighing 30 kg : For the treatment of uHCC, the recommended dosage of durvalumab is 20 mg/kg following a single dose of tremelimumab-actl 4 mg/kg at day 1 of cycle 1; then, continue durvalumab 20 mg/kg as a single agent every 4 weeks.1 Therapy should be continued until disease progression or unacceptable toxicity occurs.1
Patients Weighing 30 kg : For the treatment of primary advanced or recurrent endometrial cancer that is mismatch repair deficient (dMMR), the recommended dosage of durvalumab is 1120 mg in combination with carboplatin and paclitaxel every 3 weeks (21 days) for 6 cycles, followed by durvalumab 1500 every 4 weeks as a single agent.1 Therapy should be continued until disease progression or unacceptable toxicity occurs.1
Patients Weighing 30 kg : For the treatment of primary advanced or recurrent endometrial cancer that is mismatch repair deficient (dMMR), the recommended dosage of durvalumab is 15 mg/kg in combination with carboplatin and paclitaxel every 3 weeks (21 days) for 6 cycles, followed by durvalumab 20 mg/kg every 4 weeks as a single agent.1 Therapy should be continued until disease progression or unacceptable toxicity occurs.1
Dosage Modifications for Toxicity
If immune-mediated adverse effects or certain other adverse effects occur, temporary or permanent discontinuance of durvalumab may be required based on severity of the reaction.1 Dosage reductions of durvalumab are not recommended.1
In general, withhold durvalumab for severe (grade 3) immune-mediated adverse reactions.1 Permanently discontinue durvalumab for life-threatening (grade 4) immune-mediated adverse reactions, recurrent severe (grade 3) immune-mediated reactions that require systemic immunosuppressive treatment, or an inability to reduce corticosteroid dosage to 10 mg or less of prednisone or equivalent per day within 12 weeks of initiating corticosteroids.1 Specific recommendations that differ from these general guidelines are summarized in the Table 1.1
Type of Reaction | Severity | Modification |
|---|---|---|
Immune-mediated Adverse Reactions | ||
Pneumonitis | Grade 2 | Withhold a |
Grade 3 or 4 | Permanently discontinue | |
Colitis | Grade 2 | Withholda |
Grade 3 | ||
Grade 4 | Permanently discontinue | |
Intestinal perforation | Any grade | Permanently discontinue |
Hepatitis with no hepatic tumor involvement | ALT or AST increases to >3 and up to 8 times ULN OR total bilirubin increases to >1.5 to 3 times ULN | Withholda |
ALT or AST increases to >8 times ULN OR total bilirubin increases to >3 times ULN | Permanently discontinue | |
Hepatitis with hepatic tumor involvement c | ALT or AST increases to >1 and up to 3 times ULN at baseline and increases to no >5 and up to 10 times ULN OR ALT or AST is >3 and up to 5 times ULN at baseline and increases to >8 and up to 10 times ULN | Withholda |
ALT or AST increases to >10 times ULN OR total bilirubin increase to >3 times ULN | Permanently discontinue | |
Endocrinopathies | Grade 3 or 4 | Withhold until clinically stable or permanently discontinue depending on severity |
Nephritis with renal dysfunction | Grade 2 or 3 increased blood creatinine | Withholda |
Grade 4 increased blood creatinine | Permanently discontinue | |
Exfoliative dermatologic conditions | Suspected Stevens Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), or Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) | Withholda |
Confirmed SJS, TEN, or DRESS | Permanently discontinue | |
Myocarditis | Grade 2, 3, or 4 | Permanently discontinue |
Neurological toxicities | Grade 2 | Withholda |
Grade 3 or 4 | Permanently discontinue | |
Other Adverse Reactions | ||
Infusion-related reactions | Grade 1 or 2 | Interrupt or slow the infusion rate |
Grade 3 or 4 | Permanently discontinue |
aResume in patients with complete or partial resolution (grade 0 to 1) after corticosteroid taper.1 Permanently discontinue if no complete or partial resolution within 12 weeks of initiating corticosteroids or an inability to reduce corticosteroid dose to 10 mg of prednisone or less per day (or equivalent) within 12 weeks of initiating corticosteroids.1
bPermanently discontinue for grade 3 colitis when administered as part of a tremelimumab-actl containing regimen.1
cIf AST and ALT are less than or equal to ULN at baseline in patients with liver involvement, withhold or permanently discontinue treatment based on recommendations for hepatitis with no liver involvement.1
No dosage adjustment of durvalumab is necessary in patients with mild or moderate preexisting hepatic impairment.1, 2 Durvalumab has not been studied in patients with severe preexisting hepatic impairment, and the manufacturer provides no specific dosage recommendations for such patients.1
No dosage adjustment of durvalumab is necessary in patients with mild or moderate preexisting renal impairment.1, 2 Durvalumab has not been studied in patients with severe preexisting renal impairment, and the manufacturer provides no specific dosage recommendations for such patients.1
The manufacturer provides no specific dosage recommendations for geriatric patients.1
Immune-mediated Adverse Reactions
Durvalumab is a monoclonal antibody that belongs to a class of drugs that bind to either the programmed death receptor1 (PD-1) or the PD-ligand 1 (PD-L1), blocking the PD-1/PD-L1 pathway, thereby removing inhibition of the immune response, potentially breaking peripheral tolerance and inducing immune-mediated adverse reactions.1 Important immune-mediated adverse reactions listed may not include all possible severe and fatal immune-mediated reactions.1
The incidence and severity of immune-mediated adverse reactions were similar when durvalumab was administered as a single agent or in combination with chemotherapy or in combination with tremelimumab-actl and platinum-based chemotherapy.1
Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue.1 Immune-mediated adverse reactions can occur at any time after starting treatment with a PD 1/PD L1 blocking antibody.1 While immune-mediated adverse reactions usually manifest during treatment with PD-1/PD-L1 blocking antibodies, immune-mediated adverse reactions can also manifest after discontinuation of PD-1/PD-L1 blocking antibodies.1
Early identification and management of immune-mediated adverse reactions are essential to ensure safe use of PD-1/PD-L1 blocking antibodies.1 Monitor patients closely for symptoms and signs that may be clinical manifestations of underlying immune-mediated adverse reactions.1 Evaluate liver enzymes, creatinine, and thyroid function at baseline and periodically during treatment.1 In cases of suspected immune-mediated adverse reactions, initiate appropriate workup to exclude alternative etiologies, including infection.1 Institute medical management promptly, including specialty consultation as appropriate.1
Withhold or permanently discontinue durvalumab depending on severity.1 In general, if durvalumab requires interruption or discontinuation, administer systemic corticosteroid therapy (1 mg to 2 mg/kg per day prednisone or equivalent) until improvement to grade 1 or less.1 Upon improvement to grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month.1 Consider administration of other systemic immunosuppressants in patients whose immune-mediated adverse reactions are not controlled with corticosteroid therapy.1 Certain reactions, such as endocrinopathies and dermatologic reactions, do not necessarily require systemic steroids.1
Durvalumab can cause immune-related pneumonitis.1 The incidence of pneumonitis is higher in patients who have received prior thoracic radiation.1
Durvalumab as a Single Agent : In patients who received durvalumab as a single agent in clinical trials in which radiation therapy was generally not administered immediately prior to initiation of durvalumab, the incidence of immune-mediated pneumonitis was 2.4% (34/1414), including fatal (<0.1%), and grade 3-4 (0.4%) adverse reactions.1 Events resolved in 19 of the 34 patients and resulted in permanent discontinuation in 5 patients.1 Systemic corticosteroids were required in 19 of 34 patients with pneumonitis who did not receive chemoradiation prior to initiation of durvalumab.1
The frequency and severity of immune-mediated pneumonitis in patients who did not receive definitive chemoradiation prior to durvalumab were similar whether durvalumab was given as a single agent in patients with various cancers in a pooled data set or in patients with extensive-stage small cell lung cancer (ES-SCLC) or biliary tract cancer (BTC) when given in combination with chemotherapy.1
The incidence of pneumonitis (including radiation pneumonitis) in patients with unresectable Stage III non-small cell lung cancer (NSCLC) following definitive chemoradiation within 42 days prior to initiation of durvalumab as a single agent in PACIFIC was 18.3% (87/475) in patients receiving durvalumab and 12.8% (30/234) in patients receiving placebo.1 Of the patients who received durvalumab, 1.1% had a fatal adverse reaction and 2.7% had grade 3 adverse reactions.1 Events resolved in 50 of the 87 (57%) patients and resulted in permanent discontinuation in 27 of the 87 (31%) patients.1
The incidence of pneumonitis (including radiation pneumonitis) in patients with limited-stage small cell lung carcinoma (LS-SCLC) following chemoradiation within 42 days prior to initiation of durvalumab in ADRIATIC was 14% (37/262) in patients receiving durvalumab and 6% (16/265) in patients receiving placebo.1 Of the 262 patients who received durvalumab, 0.4% had a fatal adverse reaction and 2.7% had grade 3 adverse reactions.1 Events resolved in 19 of the 37 (51%) patients and resulted in permanent discontinuation in 18 of the 37 (49%) patients.1 Systemic corticosteroids were required in all patients, while 1 patient required use of infliximab with high-dose steroids.1
Systemic corticosteroids were required in 64 of 87 patients with pneumonitis who had received chemoradiation prior to initiation of durvalumab, while 2 patients required use of infliximab with high-dose steroids.1
Durvalumab with Tremelimumab-actl : Immune-mediated pneumonitis occurred in 1.3% (5/388) of patients receiving durvalumab in combination with tremelimumab-actl, including fatal (0.3%) and grade 3 (0.2%) adverse reactions.1 Events resolved in 3 of the 5 patients and resulted in permanent discontinuation in 1 patient.1 Systemic corticosteroids were required in all patients; of these, 4 patients required high-dose corticosteroid treatment (at least 40 mg prednisone or equivalent per day).1 One patient (1/5) required other immunosuppressants.1
Durvalumab with Tremelimumab-actl and Platinum-Based Chemotherapy : Immune-mediated pneumonitis occurred in 3.5% (21/596) of patients receiving durvalumab in combination with tremelimumab-actl and platinum-based chemotherapy, including fatal (0.5%), and grade 3 (1%) adverse reactions.1 Events resolved in 11 of the 21 patients and resulted in permanent discontinuation in 7 patients.1 Systemic corticosteroids were required in all patients with immune-mediated pneumonitis, while 1 patient required other immunosuppressants.1
Durvalumab can cause immune-mediated colitis that is frequently associated with diarrhea.1 Cytomegalovirus (CMV) infection/reactivation has been reported in patients with corticosteroid-refractory immune-mediated colitis.1 In cases of corticosteroid-refractory colitis, consider repeating infectious workup to exclude alternative etiologies.1
Immune-mediated colitis occurred in 2% (37/1889) of patients receiving durvalumab as a single agent, including grade 4 (<0.1%) and grade 3 (0.4%) adverse reactions.1 Events resolved in 27 of the 37 patients and resulted in permanent discontinuation in 8 patients.1 Systemic corticosteroids were required in all patients with immune-mediated colitis, while 2 of 37 patients required other immunosuppressants (e.g., infliximab, mycophenolate).1
Immune-mediated colitis or diarrhea occurred in 6% (23/388) of patients receiving durvalumab in combination with tremelimumab-actl, including grade 3 (3.6%) adverse reactions.1 Events resolved in 22 of the 23 patients and resulted in permanent discontinuation in 5 patients.1 All patients received systemic corticosteroids, and 20 of the 23 patients received high-dose corticosteroid treatment (at least 40 mg prednisone or equivalent per day).1 Three patients also received other immunosuppressants.1 Intestinal perforation has been observed in other studies of durvalumab in combination with tremelimumab-actl.1
Immune-mediated colitis occurred in 6.5% (39/596) of patients receiving durvalumab in combination with tremelimumab-actl and platinum-based chemotherapy, including fatal (0.2%) and grade 3 (2.5%) adverse reactions.1 Events resolved in 33 of 39 patients and resulted in permanent discontinuation in 11 patients.1 Systemic corticosteroids were required in all patients with immune-mediated colitis, while 4 of 39 patients required other corticosteroids.1 Intestinal perforation and large intestine perforation were reported in 0.1% of patients receiving durvalumab in combination with tremelimumab-actl.1
Immune-mediated hepatitis occurred in 2.8% (52/1889) of patients receiving durvalumab as a single agent, including fatal (0.2%), grade 4 (0.3%), and grade 3 (1.4%) adverse reactions.1 Events resolved in 21 of the 52 patients and resulted in permanent discontinuation of durvalumab in 6 patients.1 Systemic corticosteroids were required in all patients with immune-mediated hepatitis, while 2 of 52 patients required use of mycophenolate with high-dose steroids.1
Immune-mediated hepatitis occurred in 7.5% (29/388) of patients receiving durvalumab in combination with tremelimumab-actl, including fatal (0.8%), grade 4 (0.3%), and grade 3 (4.1%) adverse reactions.1 Events resolved in 12 of the 29 patients and resulted in permanent discontinuation in 9 patients.1 Systemic corticosteroids were required in all 29 patients and all 29 patients required high-dose corticosteroid treatment (at least 40 mg prednisone or equivalent per day).1 Eight of 29 patients required other immunosuppressants.1
Immune-mediated hepatitis occurred in 3.9% (23/596) of patients receiving durvalumab in combination with tremelimumab-actl and platinum-based chemotherapy, including fatal (0.3%), grade 4 (0.5%), and grade 3 (2.0%) adverse reactions.1 Events resolved in 12 of the 23 patients and resulted in permanent discontinuation in 10 patients.1 Systemic corticosteroids were required in all patients with immune-mediated hepatitis, while 2 of 23 patients required use of other immunosuppressants.1
Immune-mediated Endocrinopathies
Adrenal Insufficiency : Durvalumab can cause primary or secondary adrenal insufficiency.1 For grade 2 or higher adrenal insufficiency, initiate symptomatic treatment, including hormone replacement as clinically indicated.1 Withhold or permanently discontinue durvalumab based on the severity.1
Immune-mediated adrenal insufficiency occurred in 0.5% (9/1889) of patients receiving durvalumab as a single agent, including grade 3 (<0.1%) adverse reactions.1 Events resolved in 1 of the 9 patients and did not lead to permanent discontinuation of durvalumab in any patients.1 Systemic corticosteroids were required in all patients with adrenal insufficiency; of these, the majority remained on systemic corticosteroids.1
Immune-mediated adrenal insufficiency occurred in 1.5% (6/388) of patients receiving durvalumab in combination with tremelimumab-actl, including grade 3 (0.3%) adverse reactions.1 Events resolved in 2 of the 6 patients.1 Systemic corticosteroids were required in all 6 patients, and of these, 1 patient required high-dose corticosteroid treatment (at least 40 mg prednisone or equivalent per day).1
Immune-mediated adrenal insufficiency occurred in 2.2% (13/596) of patients receiving durvalumab in combination with tremelimumab-actl and platinum-based chemotherapy, including grade 3 (0.8%) adverse reactions.1 Events resolved in 2 of the 13 patients and resulted in permanent discontinuation in 1 patient.1 Systemic corticosteroids were required in all patients with adrenal insufficiency.1 One patient also required endocrine therapy.1
Hypophysitis : Durvalumab can cause immune-mediated hypophysitis.1 Hypophysitis can present with acute symptoms associated with mass effect such as headache, photophobia, or visual field cuts.1 Hypophysitis can cause hypopituitarism.1 Initiate symptomatic treatment including hormone replacement as clinically indicated.1 Withhold or permanently discontinue durvalumab depending on severity.1
Grade 3 hypophysitis/hypopituitarism occurred in <0.1% (1/1889) of patients who received durvalumab as a single agent.1 Treatment with systemic corticosteroids was administered in this patient.1 The event did not lead to permanent discontinuation of durvalumab.1
Immune-mediated hypophysitis/hypopituitarism occurred in 1% (4/388) of patients receiving durvalumab in combination with tremelimumab-actl.1 Events resolved in 2 of the 4 patients.1 Systemic corticosteroids were required in 3 patients, and of these, 1 patient received high-dose corticosteroid treatment (at least 40 mg prednisone or equivalent per day).1 Two patients also required endocrine therapy.1
Immune-mediated hypophysitis occurred in 1.3% (8/596) of patients receiving durvalumab in combination with tremelimumab-actl and platinum-based chemotherapy, including grade 3 (0.5%) adverse reactions.1 Events resulted in permanent discontinuation in 1 patient.1 Systemic corticosteroids were required in 6 patients with immune-mediated hypophysitis; of these, 2 of the 8 patients received high-dose corticosteroid treatment (at least 40 mg prednisone or equivalent per day).1 Four patients also required endocrine therapy.1
Thyroid Disorders : Durvalumab can cause immune-mediated thyroid disorders.1 Thyroiditis can present with or without endocrinopathy.1 Hypothyroidism can follow hyperthyroidism.1 Initiate hormone replacement therapy for hypothyroidism or institute medical management of hyperthyroidism as clinically indicated.1 Withhold or discontinue durvalumab based on the severity.1
Thyroiditis: Immune-mediated thyroiditis occurred in 0.5% (9/1889) of patients receiving durvalumab as a single agent, including grade 3 (<0.1%) adverse reactions.1 Events resolved in 4 of the 9 patients and resulted in permanent discontinuation in 1 patient.1 Systemic corticosteroids were required in 3 patients (3/9) with immune-mediated thyroiditis, while 8 of 9 patients required endocrine therapy.1
Immune-mediated thyroiditis occurred in 1.5% (6/388) of patients receiving durvalumab in combination with tremelimumab-actl.1 Events resolved in 2 of the 6 patients.1 Systemic corticosteroids were required in 2 of 6 patients with immune-mediated thyroiditis; of these, 1 patient required high-dose corticosteroid treatment (at least 40 mg prednisone or equivalent per day).1 All patients required other therapy including hormone replacement therapy, thiamazole, carbimazole, propylthiouracil, perchlorate, calcium channel blocking agent, or β-adrenergic blocking agent.1
Immune-mediated thyroiditis occurred in 1.2% (7/596) of patients receiving durvalumab in combination with tremelimumab-actl and platinum-based chemotherapy.1 Events resolved in 2 of the 7 patients and one resulted in permanent discontinuation.1 Systemic corticosteroids were required in 2 of 7 patients with immune-mediated thyroiditis, while all patients required endocrine therapy.1
Hyperthyroidism: Immune-mediated hyperthyroidism occurred in 2.1% (39/1889) of patients receiving durvalumab as a single agent.1 Events resolved in 30 of the 39 patients and did not lead to permanent discontinuation of durvalumab in any patients.1 Systemic corticosteroids were required in 9 patients (9/39) with immune-mediated hyperthyroidism, while 35 patients (35/39) required endocrine therapy.1
Immune-mediated hyperthyroidism occurred in 4.6% (18/388) of patients receiving durvalumab in combination with tremelimumab-actl, including grade 3 (0.3%) adverse reactions.1 Events resolved in 15 of the 18 patients.1 Two patients (2/18) required high-dose corticosteroid treatment (at least 40 mg prednisone or equivalent per day).1 Seventeen patients required other therapy (thiamazole, carbimazole, propylthiouracil, perchlorate, calcium channel blocking agent, or β-adrenergic blocking agent).1
Immune-mediated hyperthyroidism occurred in 5% (30/596) of patients receiving durvalumab in combination with tremelimumab-actl and platinum-based chemotherapy, including grade 3 (0.2%) adverse reactions.1 Events resolved in 21 of the 30 patients.1 Systemic corticosteroids were required in 5 of 30 patients with immune-mediated hyperthyroidism, while 28 patients (28/30) required endocrine therapy.1
Hypothyroidism: Immune-mediated hypothyroidism occurred in 8.3% (156/1889) of patients receiving durvalumab as a single agent, including grade 3 (<0.1%) adverse reactions.1 Events resolved in 31 of the 156 patients and did not lead to permanent discontinuation of durvalumab in any patients.1 Systemic corticosteroids were required in 11 patients, and the majority of patients required long-term thyroid hormone replacement.1
Immune-mediated hypothyroidism occurred in 11% (42/388) of patients receiving durvalumab in combination with tremelimumab-actl.1 Events resolved in 5 of the 42 patients.1 One patient received high-dose corticosteroid treatment (at least 40 mg prednisone or equivalent per day).1 All patients required other therapy (thiamazole, carbimazole, propylthiouracil, perchlorate, calcium channel blocking agent, or β-adrenergic blocking agent).1
Immune-mediated hypothyroidism occurred in 8.6% (51/596) of patients receiving durvalumab in combination with tremelimumab-actl and platinum-based chemotherapy, including grade 3 (0.5%) adverse reactions.1 Systemic corticosteroids were required in 2 patients, and all patients required endocrine therapy.1
Immune-mediated hypothyroidism occurred in 14% (34/235) of patients receiving durvalumab in combination with carboplatin and paclitaxel.1 Events resolved in 8 of the 34 patients.1 Endocrine therapy was required in all 34 patients.1
Type 1 Diabetes, which can Present with Diabetic Ketoacidosis : Monitor patients for hyperglycemia or other signs and symptoms of diabetes.1 Initiate treatment with insulin as clinically indicated.1 Withhold or permanently discontinue durvalumab based on the severity.1
Grade 3 immune-mediated type 1 diabetes mellitus occurred in <0.1% (1/1889) of patients receiving durvalumab as a single agent.1 This patient required long-term insulin therapy and durvalumab was permanently discontinued.1 Two additional patients (0.1%, 2/1889) had events of hyperglycemia requiring insulin therapy that did not resolve at the time of reporting.1
Two patients (0.5%; 2/388) receiving durvalumab in combination with tremelimumab-actl had events of hyperglycemia requiring insulin therapy that had not resolved at last follow-up.1
Immune-mediated Type 1 diabetes mellitus occurred in 0.5% (3/596) of patients receiving durvalumab in combination with tremelimumab-actl and platinum-based chemotherapy, including grade 3 (0.3%) adverse reactions.1 All patients required endocrine therapy.1
Immune-mediated Nephritis with Renal Dysfunction
Immune-mediated nephritis occurred in 0.5% (10/1889) of patients receiving durvalumab as a single agent, including grade 3 (<0.1%) adverse reactions.1 Events resolved in 5 of the 10 patients and resulted in permanent discontinuation in 3 patients.1 Systemic corticosteroids were required in all patients with immune-mediated nephritis.1
Immune-mediated nephritis occurred in 1% (4/388) of patients receiving durvalumab in combination with tremelimumab-actl, including grade 3 (0.5%) adverse reactions.1 Events resolved in 3 of the 4 patients and resulted in permanent discontinuation in 2 patients.1 Systemic corticosteroids were required in all patients with immune-mediated nephritis; of these, 3 patients required high-dose corticosteroid treatment (at least 40 mg prednisone or equivalent per day).1
Immune-mediated nephritis occurred in 0.7% (4/596) of patients receiving durvalumab in combination with tremelimumab-actl and platinum-based chemotherapy, including grade 3 (0.2%) adverse reactions.1 Events resolved in 1 of the 4 patients and resulted in permanent discontinuation in 3 patients.1 Systemic corticosteroids were required in all patients with immune-mediated nephritis.1
Immune-mediated Dermatologic Reactions
Durvalumab can cause immune-mediated rash or dermatitis.1 Exfoliative dermatitis, including Stevens Johnson Syndrome (SJS), drug rash with eosinophilia and systemic symptoms (DRESS), and toxic epidermal necrolysis (TEN), has occurred with PD-1/L-1 blocking antibodies.1 Topical emollients and/or topical corticosteroids may be adequate to treat mild to moderate non-exfoliative rashes.1 Withhold or permanently discontinue durvalumab depending on severity.1
Immune-mediated rash or dermatitis occurred in 1.8% (34/1889) of patients receiving durvalumab as a single agent, including grade 3 (0.4%) adverse reactions.1 Events resolved in 19 of the 34 patients and resulted in permanent discontinuation in 2 patients.1 Systemic corticosteroids were required in all patients with immune-mediated rash or dermatitis.1
Immune-mediated rash or dermatitis occurred in 4.9% (19/388) of patients receiving durvalumab in combination with tremelimumab-actl, including grade 4 (0.3%) and grade 3 (1.5%) adverse reactions.1 Events resolved in 13 of the 19 patients and resulted in permanent discontinuation in 2 patients.1 Systemic corticosteroids were required in all patients with immune-mediated rash or dermatitis; of these, 12 patients required high-dose corticosteroid treatment (at least 40 mg prednisone or equivalent per day).1 One patient received other immunosuppressants.1
Immune-mediated rash or dermatitis occurred in 7.2% (43/596) of patients receiving durvalumab in combination with tremelimumab-actl and platinum-based chemotherapy, including grade 3 (0.3%) adverse reactions.1 Events resolved in 32 of the 43 patients and resulted in permanent discontinuation in 2 patients.1 Systemic corticosteroids were required in all patients with immune-mediated rash or dermatitis.1
Immune-mediated pancreatitis occurred in 2.3% (9/388) of patients receiving durvalumab in combination with tremelimumab-actl, including grade 4 (0.3%) and grade 3 (1.5%) adverse reactions.1 Events resolved in 6 of the 9 patients.1 Systemic corticosteroids were required in all 9 patients, and of these, 7 patients required high-dose corticosteroid treatment (at least 40 mg prednisone or equivalent per day).1
Other Immune-mediated Adverse Reactions
Other clinically important, immune-mediated adverse reactions that occurred at an incidence of less than 1% each in patients who received durvalumab or durvalumab in combination with tremelimumab-actl, or were reported with the use of other PD-1/PD-L1 blocking antibodies, involved the following general systems: cardiac/vascular, nervous system, ocular, gastrointestinal, musculoskeletal, connective tissue, endocrine, hematologic, and immune systems.1
Durvalumab can cause severe or life-threatening infusion-related reactions.1 Monitor for signs and symptoms of infusion-related reactions.1 Interrupt, slow the rate of, or permanently discontinue durvalumab based on the severity.1 For grade 1 or 2 infusion-related reactions, consider using pre-medications with subsequent doses.1
Infusion-related reactions occurred in 2.2% (42/1889) of patients receiving durvalumab as a single agent, including grade 3 (0.3%) adverse reactions.1
Infusion-related reactions occurred in 2.6% (10/388) patients receiving durvalumab in combination with tremelimumab-actl.1
Infusion-related reactions occurred in 2.9% (17/596) of patients receiving durvalumab in combination with tremelimumab-actl and platinum-based chemotherapy, including grade 3 (0.3%) adverse reactions.1
Complications of Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) After Durvalumab
Fatal and other serious complications can occur in patients who receive allogeneic hematopoietic stem cell transplantation (HSCT) before or after being treated with a PD-1/L-1 blocking antibody.1 Transplant-related complications include hyperacute graft-versus-host-disease (GVHD), acute GVHD, chronic GVHD, hepatic veno-occlusive disease (VOD) after reduced intensity conditioning, and steroid-requiring febrile syndrome (without an identified infectious cause).1 These complications may occur despite intervening therapy between PD-1/L-1 blockade and allogeneic HSCT.1
Follow patients closely for evidence of transplant-related complications and intervene promptly.1 Consider the benefits versus risks of treatment with a PD-1/L-1 blocking antibody prior to or after an allogeneic HSCT. 1
Fetal/Neonatal Morbidity and Mortality
Based on the mechanism of action of durvalumab and data from animal studies, the drug can cause fetal harm when administered to pregnant women.1 In animal reproduction studies, administration of durvalumab to cynomolgus monkeys from the onset of organogenesis through delivery resulted in increased premature delivery, fetal loss, and premature neonatal death.1
Verify pregnancy status in women of reproductive potential prior to initiation of durvalumab.1 Advise pregnant women of the potential risk to a fetus.1 Advise females of reproductive potential to use effective contraception during treatment with durvalumab and for 3 months after the last dose.1
In patients who received durvalumab across the PACIFIC, CASPIAN, TOPAZ-1, HIMALAYA, POSEIDON, DUO-E, AEGEAN, and other clinical trials, 3.2% of evaluable patients tested positive for anti-durvalumab antibodies, and 19.2% of patients positive for anti-drug antibodies (ADAs) had neutralizing antibodies against durvalumab.1 No clinically important effects of ADAs on durvalumab pharmacokinetics or safety were identified; however, the effect of these ADAs on the effectiveness of durvalumab is unknown.1
Based on findings from animal studies and the mechanism of action of durvalumab, the drug can cause fetal harm when administered to pregnant women.1 There are no available data on use of durvalumab in pregnant women.1
In animal reproduction studies, administration of durvalumab to pregnant cynomolgus monkeys from the confirmation of pregnancy through delivery at exposure levels approximately 6—20 times higher than those observed at the clinical dose of 10 mg/kg based on AUC, resulted in an increase in premature delivery, fetal loss, and premature neonatal death.1
Human immunoglobulin G1 (IgG1) is known to cross the placental barrier; therefore, durvalumab has the potential to be transmitted from the mother to the developing fetus.1 Apprise pregnant women of the potential risk to a fetus.1
There are no data on the presence of durvalumab in human milk, its effects on the breast-fed child, or the effects on milk production.1 Maternal IgG is known to be present in human milk.1 The effects of local GI exposure and limited systemic exposure in the breast-fed child to durvalumab are unknown.1
Durvalumab was present in the milk of lactating cynomolgus monkeys and was associated with premature neonatal death.1
Because of the potential for adverse reactions in a breast-fed child, advise women not to breast-feed during treatment with durvalumab and for 3 months after the last dose.1
Females and Males of Reproductive Potential
Verify pregnancy status in women of reproductive potential prior to initiation of durvalumab.1
Durvalumab can cause fetal harm when administered to a pregnant woman.1 Advise women of reproductive potential to use effective contraception during treatment with durvalumab and for 3 months following the last dose.1
Safety and efficacy of durvalumab have not been established in pediatric patients.1
Of the 401 patients with resectable non-small cell lung cancer (NSCLC) treated with durvalumab in combination with chemotherapy in the AEGEAN study, 209 (52%) patients were ≥65 years of age and 49 (12%) patients were ≥75 years of age.1 There were no overall clinically important differences in safety or efficacy between patients ≥65 years of age and younger patients.1
Of the 476 patients with unresectable, Stage III NSCLC treated with durvalumab in the PACIFIC study, 45% of patients were ≥65 years of age while 7.6% were ≥75 years of age.1 No overall differences in safety or effectiveness were observed between patients 65 years or older and younger patients.1 The PACIFIC study did not include sufficient numbers of patients ≥75 years of age to determine whether they respond differently from younger patients.1
Of the 330 patients with metastatic NSCLC treated with durvalumab in combination with tremelimumab-actl and platinum-based chemotherapy, 143 (43%) patients were ≥65 years of age and 35 (11%) patients were ≥75 years of age.1 There were no clinically important differences in safety or efficacy between patients ≥65 years of age and younger patients.1
Of the 262 patients with limited-stage small cell lung cancer (LS-SCLC) treated with durvalumab, 103 (39%) patients were ≥65 years of age and 15 (6%) were ≥75 years of age.1 There were no clinically important differences in safety and efficacy between patients ≥65 years of age and younger patients.1
Of the 265 patients with ES-SCLC treated with durvalumab in combination with chemotherapy, 101 (38%) patients were ≥65 years of age and 19 (7.2%) patients were ≥75 years of age.1 There were no clinically important differences in safety or efficacy between patients ≥65 years of age and younger patients.1
Of the 338 patients with BTC treated with durvalumab in combination with chemotherapy in the TOPAZ-1 study, 158 (47%) patients were ≥65 years of age and 38 (11%) patients were ≥75 years of age.1 No overall differences in safety or effectiveness of durvalumab have been observed between patients ≥65 years of age and younger adults.1
Of the 393 patients with unresectable hepatocellular carcinoma (uHCC) treated with durvalumab in combination with tremelimumab-actl, 50% of patients were ≥65 years of age and 13% of patients were ≥75 years of age.1 No overall differences in safety or effectiveness of durvalumab have been observed between patients ≥65 years of age and younger adults.1
Of the 235 patients with endometrial cancer treated with durvalumab with carboplatin and paclitaxel, 49% of patients were ≥65 years of age and 12% of patients were ≥75 years of age.1 No overall differences in safety or effectiveness of durvalumab have been observed between patients ≥65 years of age and younger adults.1
There were no clinically important differences in the pharmacokinetics of durvalumab in mild or moderate hepatic impairment (bilirubin ≤3x upper limit of normal [ULN] and any AST).1 The effect of severe hepatic impairment (bilirubin >3x ULN and any AST) on durvalumab pharmacokinetics is unknown.1
There were no clinically important differences in the pharmacokinetics of durvalumab in mild or moderate renal impairment (creatinine clearance 30—89 mL/min).1 The effect of severe renal impairment (creatinine clearance 15—29 mL/min) on durvalumab pharmacokinetics is unknown.1
Durvalumab with Chemotherapy : The most common adverse reactions (≥20% of patients with resectable, Stage II/III NSCLC [neoadjuvant /adjuvant]) are anemia, nausea, constipation, fatigue, musculoskeletal pain, and rash.1
Durvalumab as a Single Agent : The most common adverse reactions (≥20% of patients with unresectable, Stage III NSCLC) are cough, fatigue, pneumonitis/radiation pneumonitis, upper respiratory tract infections, dyspnea, and rash.1 The most common adverse reactions (≥20% of patients with LS-SCLC) are pneumonitis or radiation pneumonitis, and fatigue.1
Durvalumab with Tremelimumab-actl and Platinum-Based Chemotherapy : The most common adverse reactions (≥20% of patients with metastatic NSCLC) were nausea, fatigue, musculoskeletal pain, decreased appetite, rash, and diarrhea.1
Durvalumab with Platinum-Based Chemotherapy : The most common adverse reactions (≥20% of patients with ES-SCLC) are nausea, fatigue/asthenia, and alopecia.1
Durvalumab with Gemcitabine and Cisplatin : The most common adverse reactions (≥20% of patients with BTC) are fatigue, nausea, constipation, decreased appetite, abdominal pain, rash, and pyrexia.1
Durvalumab with Tremelimumab-actl : The most common adverse reactions (≥20% of patients with uHCC) are rash, diarrhea, fatigue, pruritus, musculoskeletal pain, and abdominal pain.1
Durvalumab with Carboplatin and Paclitaxel, followed by Durvalumab as a Single Agent : The most common adverse reactions (≥20% of patients with endometrial cancer) were peripheral neuropathy, musculoskeletal pain, nausea, alopecia, fatigue, abdominal pain, constipation, rash, decreased magnesium, increased ALT, increased AST, diarrhea, vomiting, cough, decreased potassium, dyspnea, headache, and increased alkaline phosphatase.1
No formal drug interaction studies have been performed to date.1
No cytochrome P-450 (CYP) based drug interactions are anticipated since durvalumab is a monoclonal antibody.2
Durvalumab, a recombinant fully human anti-programmed-death ligand-1 (anti-PD-L1) monoclonal antibody, is an antineoplastic agent.1 The drug is an IgG1 kappa immunoglobulin that binds to PD-L1.1
The immune-checkpoint receptor programmed-death receptor-1 (PD-1) is expressed on activated T cells, B cells, macrophages, and dendritic cells.7, 8, 9 Overexpression of PD-1 ligands on the surface of tumor cells results in activation of PD-1 and CD80 (i.e., B7.1) and suppression of cytotoxic T-cell activity, T-cell proliferation, and cytokine production.1, 8 Durvalumab blocks the interaction between PD-L1 and the receptors PD-1 and CD80, resulting in activation of the antitumor immune response without inducing antibody-dependent cell-mediated cytotoxicity (ADCC).1, 8, 10 The drug also has been shown to reduce tumor growth in mouse tumor models.1, 9
Pharmacokinetic exposure of durvalumab increased more than dose proportionally at doses <3 mg/kg (0.3 times the approved recommended dosage) and dose proportionally at doses ≥3 mg/kg every 2 weeks.1 Steady state was achieved at approximately 16 weeks.1 The pharmacokinetics of durvalumab is similar when assessed as a single agent, when in combination with chemotherapy, when in combination with tremelimumab-actl, and when in combination with tremelimumab-actl and platinum-based chemotherapy.1 Durvalumab clearance decreases over time.1 The elimination half-life is approximately 21 days.1
There were no clinically important differences in the pharmacokinetics of durvalumab based on body weight, age, sex, race, albumin levels, lactate dehydrogenase levels, soluble PD-L1, tumor type, mild or moderate renal impairment, and mild or moderate hepatic impairment.1 The effect of severe renal or hepatic impairment on the pharmacokinetics of durvalumab is unknown.1
Additional Information
The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer's labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Parenteral | Concentrate, for injection, for IV infusion | 50 mg/mL (120 and 500 mg) |
AHFS® Drug Information. © Copyright, 1959-2026, Selected Revisions June 10, 2025. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, MD 20814.
1. AstraZeneca. Imfinzi® (durvalumab) injection for intravenous infusion prescribing information. Wilmington, DE; 2025 Feb.
2. Food and Drug Administration. Center for Drug Evaluation and Research. Application number 761069Orig1s000: Summary review(s). From FDA website. [Web]
4. Food and Drug Administration. Search orphan drug designations and approvals. From FDA website. Accessed 2025 Mar 18.
7. Bellmunt J, Powles T, Vogelzang NJ. A review on the evolution of PD-1/PD-L1 immunotherapy for bladder cancer: The future is now. Cancer Treat Rev . 2017; 54:58-67. [PubMed 28214651]
8. Lee HT, Lee JY, Lim H et al. Molecular mechanism of PD-1/PD-L1 blockade via anti-PD-L1 antibodies atezolizumab and durvalumab. Sci Rep . 2017; 7:5532. [PubMed 28717238]
9. Stewart R, Morrow M, Hammond SA et al. Identification and Characterization of MEDI4736, an Antagonistic Anti-PD-L1 Monoclonal Antibody. Cancer Immunol Res . 2015; 3:1052-62. [PubMed 25943534]
10. Syed YY. Durvalumab: First Global Approval. Drugs . 2017; 77:1369-1376. [PubMed 28643244]
11. Antonia SJ, Villegas A, Daniel D et al. Durvalumab after Chemoradiotherapy in Stage III Non-Small-Cell Lung Cancer. N Engl J Med . 2017; 377:1919-29. [PubMed 28885881]
12. Antonia SJ, Villegas A, Daniel D et al. Overall Survival with Durvalumab after Chemoradiotherapy in Stage III NSCLC. N Engl J Med . 2018; 379:2342-50. [PubMed 30280658]
14. Heymach JV, Harpole D, Mitsudomi T et al., for the AEGEAN Investigators. Perioperative Durvalumab for Resectable Non-Small-Cell Lung Cancer. N Engl J Med. 2023;389(18):1672-1684.
15. Spigel DR, Faivre-Finn C, Gray JE et al., on behalf of the PACIFIC Investigators. Five-Year Survival Outcomes From the PACIFIC Trial: Durvalumab After Chemoradiotherapy in Stage III Non-Small-Cell Lung Cancer. J Clin Oncol. 2022;40(12):1301-1311.
16. Johnson ML, Cho BC, Luft A et al., for the POSEIDON Investigators. Durvalumab With or Without Tremelimumab in Combination With Chemotherapy as First-Line Therapy for Metastatic Non-Small-Cell Lung Cancer: The Phase III POSEIDON Study. J Clin Oncol. 2023;41(6):1213-1227.
17. Daly ME, Singh N, Ismaila N, et al. Management of Stage III Non-Small-Cell Lung Cancer: ASCO Guideline. J Clin Oncol. 2022;40(12):1356-1384.
18. Leighl NB, Ismaila N, Durm G, et al. Therapy for Stage IV Non-Small Cell Lung Cancer Without Driver Alterations: ASCO Living Guideline, Version 2024.3. J Clin Oncol. Published online February 27, 2025.
19. Cheng Y, Spigel DR, Cho BC et al., for the ADRIATIC Investigators. Durvalumab after Chemoradiotherapy in Limited-Stage Small-Cell Lung Cancer. N Engl J Med. 2024;391(14):1313-1327.
20. Paz-Ares L, Dvorkin M, Chen Y et al., for the CASPIAN Investigators. Durvalumab plus platinum-etoposide versus platinum-etoposide in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): a randomised, controlled, open-label, phase 3 trial. Lancet. 2019;394(10212):1929-1939.
21. Goldman JW, Dvorkin M, Chen Y et al., for the CASPIAN Investigators. Durvalumab, with or without tremelimumab, plus platinum-etoposide versus platinum-etoposide alone in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): updated results from a randomised, controlled, open-label, phase 3 trial. Lancet Oncol. 2021;22(1):51-65.
22. Khurshid H, Ismaila N, Bian J, et al. Systemic Therapy for Small-Cell Lung Cancer: ASCO-Ontario Health (Cancer Care Ontario) Guideline. J Clin Oncol. 2023;41(35):5448-5472.
23. Kalemkerian GP, Khurshid H, Ismaila N, for the Systemic Therapy for Small Cell Lung Cancer Guideline Expert Panel. Systemic Therapy for Small Cell Lung Cancer: ASCO Guideline Rapid Recommendation Update. J Clin Oncol. 2025;43(1):101-105.
24. Oh DY, Ruth He A, Qin S et al., for the TOPAZ-1 Investigators. Durvalumab plus Gemcitabine and Cisplatin in Advanced Biliary Tract Cancer. NEJM Evid. 2022;1(8):EVIDoa2200015.
25. Oh DY, He AR, Bouattour M, et al. Durvalumab or placebo plus gemcitabine and cisplatin in participants with advanced biliary tract cancer (TOPAZ-1): updated overall survival from a randomised phase 3 study. Lancet Gastroenterol Hepatol. 2024;9(8):694-704.
26. Vogel A, Bridgewater J, Edeline J et al., on behalf of the ESMO Guidelines Committee. Biliary tract cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. Ann Oncol. 2023;34(2):127-140.
27. Vogel A, Ducreux M, on behalf of the ESMO Guidelines Committee. Electronic address: [email protected]. ESMO Clinical Practice Guideline interim update on the management of biliary tract cancer. ESMO Open. 2025;10(1):104003.
28. Abou-Alfa GK, Lau G, Kudo M et al., for the HIMALAYA Investigators. Tremelimumab plus Durvalumab in Unresectable Hepatocellular Carcinoma. NEJM Evid. 2022;1(8):EVIDoa2100070.
29. Sangro B, Chan SL, Kelley RK et al., for the HIMALAYA Investigators. Four-year overall survival update from the phase III HIMALAYA study of tremelimumab plus durvalumab in unresectable hepatocellular carcinoma. Ann Oncol. 2024;35(5):448-457.
30. Gordan JD, Kennedy EB, Abou-Alfa GK, et al. Systemic Therapy for Advanced Hepatocellular Carcinoma: ASCO Guideline Update. J Clin Oncol. 2024;42(15):1830-1850.
31. Westin SN, Moore K, Chon HS et al., on behalf of the DUO-E Investigators. Durvalumab Plus Carboplatin/Paclitaxel Followed by Maintenance Durvalumab With or Without Olaparib as First-Line Treatment for Advanced Endometrial Cancer: The Phase III DUO-E Trial J Clin Oncol. 2024;42(3):283-299.
32. Practice Bulletin No. 149: Endometrial cancer. Obstet Gynecol. 2015;125(4):1006-1026.
33. Singal AG, Llovet JM, Yarchoan M et al. AASLD Practice Guidance on prevention, diagnosis, and treatment of hepatocellular carcinoma. Hepatology. 2023 Dec 1;78(6):1922-1965.