Tucatinib, a highly selective, reversible tyrosine kinase inhibitor of human epidermal growth factor receptor type 2 (HER2), is an antineoplastic agent.1, 9, 14, 15, 16, 18
Combination Therapy with Trastuzumab and Capecitabine
Tucatinib is used in combination with trastuzumab and capecitabine for the treatment of human epidermal growth factor receptor type 2 (HER2)-positive advanced unresectable or metastatic breast cancer in adults, including those with brain metastases, who have previously received at least one anti-HER2-based regimen in the metastatic setting.1, 11, 20 The drug has been designated an orphan drug by FDA for the treatment of breast cancer patients with brain metastases.6
Efficacy of tucatinib for this use is based principally on the results of a randomized, double-blind, placebo-controlled phase 2 study (HER2CLIMB) in adults with HER2-positive, unresectable, locally advanced, or metastatic breast cancer (with or without brain metastases) previously treated with trastuzumab, pertuzumab, or ado-trastuzumab emastine (separately or in combination) in the neoadjuvant, adjuvant, or metastatic setting.1, 11, 16 In this study, 612 patients were randomized (stratified by presence or history of brain metastases, Eastern Cooperative Oncology Group [ECOG] performance status, and geographic region) in a 2:1 ratio to receive either tucatinib 300 mg orally twice daily in combination with trastuzumab (8 mg/kg IV initially, followed by either 6 mg/kg IV or 600 mg by subcutaneous injection on day 1 of each 21-day cycle) and capecitabine (1 g/m2 orally twice daily on days 1-14 of each 21-day cycle) or placebo in combination with trastuzumab and capecitabine.1, 11 Treatment was continued until disease progression or unacceptable toxicity occurred.1 The primary measure of efficacy was progression-free survival (as assessed by a blinded independent central review committee) according to Response Evaluation Criteria in Solid Tumors (RECIST v1.1).1, 11 In the primary efficacy population (consisting of the initial 480 patients randomized in the study), the median age of patients was 54 years; 73% of the patients were white, 99% were female, 51% had an ECOG performance status of 1, 60% had estrogen and/or progesterone receptor-positive disease, and 74% had visceral metastases.1 Approximately one-half (48%) of patients had active brain metastases or a history of brain metastases; 23% of these patients had untreated brain metastases, 40% had previously treated but stable brain metastases, and 37% had previously treated but radiographically progressing brain metastases.1 Patients had received a median of 4 prior systemic therapies or a median of 3 prior systemic therapies in the metastatic setting; all patients had previously received trastuzumab and ado-trastuzumab emtansine and all but 2 patients had previously received pertuzumab.1 This study excluded patients with leptomeningeal disease.1
In the primary efficacy population, patients receiving tucatinib in combination with trastuzumab and capecitabine had a longer median progression-free survival than those receiving the placebo combination regimen (7.8 versus 5.6 months).1, 11 In the total patient population, median overall survival also was prolonged in patients receiving the tucatinib combination regimen compared with those receiving the placebo regimen (21.9 versus 17.4 months).1, 11 Among the patients with a history or presence of parenchymal brain metastases at baseline, median progression-free survival in patients receiving the tucatinib or placebo combination regimen was 7.6 or 5.4 months, respectively.1 Among patients with measurable disease, patients receiving the tucatinib combination regimen also had higher objective response rates compared with those receiving the placebo combination regimen (40.6% versus 22.8%); complete response was achieved in 0.9 or 1.2% of patients receiving these respective treatments.1, 11 At the time of analysis, the median duration of response was 8.3 months in patients receiving the tucatinib combination regimen and 6.3 months in those receiving the placebo combination regimen.1 Exploratory analyses of the cohort of patients with a history or presence of brain metastases at baseline also suggested prolonged progression-free survival (9.9 versus 4.2 months) and overall survival (18.1 versus 12 months) and higher rates of objective response (47.3 versus 20%) in patients receiving the tucatinib combination regimen compared with those receiving the placebo combination regimen.19
Combination Therapy with Trastuzumab
Tucatinib is used in combination with trastuzumab for the treatment of adults with RAS wild-type, HER2-positive unresectable or metastatic colorectal cancer that has progressed following treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy.1 Patients should be selected for therapy based on the presence of HER2 overexpression or gene amplification (FDA tests are not currently available) and RAS wild-type mutations (FDA-approved tests are available, see [Web]).1 The drug has been designated an orphan drug by the FDA for treatment of HER2-positive colorectal cancer.6 This indication is approved under accelerated approval based on tumor response rate and durability of response.1 Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.1
Efficacy of tucatinib for this use is based principally on the results of an open-label, multicenter trial (MOUNTAINEER) in 84 patients with HER2-positive, RAS wild-type, unresectable or metastatic colorectal cancer and who received prior treatment (fluoropyrimidines, oxaliplatin, irinotecan, and anti-vascular endothelial growth factor [VEGF] monoclonal antibody).1, 22 Patients whose disease had deficient mismatch repair (dMMR) proteins or microsatellite instability-high (MSI-H) must have also received an anti-programmed cell death protein-1 (PD-1) monoclonal antibody and patients who received prior anti-HER2 targeting therapy were excluded.1 The median age of patients was 55 years (range: 24 to 77); 14% of patients were 65 years of age or older, 61% were male, 77% of patients were white, 4% were Black, 4% were Asian, and 4% were Hispanic or Latino.1 In this study, 70% of patients had lung metastases, 64% had liver metastases, 60% had an ECOG performance status of 0, 37% had an ECOG performance status of 1, and 4% had an ECOG performance status of 2.1 Prior treatment with fluoropyrimidine, oxaliplatin, and irinotecan occurred in 99% of patients and 83% and 52% of patients received anti-VEGF antibodies and anti-EGFR antibodies, respectively; 23%, 38%, and 39% of patients received 1, 2, or ≥3 prior lines of therapy, respectively.1 Patients received tucatinib 300 mg orally twice daily with a loading dose of trastuzumab (or a non-US approved trastuzumab product) 8 mg/kg IV on day 1 of cycle 1, followed by a maintenance dose of trastuzumab 6 mg/kg on day 1 of each subsequent 21-day cycle.1 Patients were treated until disease progression or unacceptable toxicity occurred.1
The major efficacy outcome measures were overall response rate and duration of response.1 At the time of evaluation, the overall response rate was 38%, with 3.6% of patients having a complete response and 35% a partial response.1 22 The median duration of response was 12.4 months; 81% of patients had a duration of response ≥6 months and 34% had a duration of response ≥12 months.1
Dispensing and Administration Precautions
Tucatinib is administered orally twice daily (approximately every 12 hours), at the same time each day, without regard to meals.1 Tucatinib tablets should be swallowed intact and should not be chewed, crushed, broken, cracked, or split.1
If a dose of tucatinib is missed or vomited, the next dose should be taken at the regularly scheduled time.1
For use in combination with trastuzumab and capecitabine for the treatment of HER2-positive advanced unresectable or metastatic breast cancer, the recommended adult dosage of tucatinib is 300 mg twice daily.1 Therapy should be continued until disease progression or unacceptable toxicity occurs.1
Clinicians should consult the manufacturers' labelings or published protocols for information on the dosage, method of administration, and administration sequence of other antineoplastic agents used in combination regimens.1
Tucatinib and capecitabine may be administered at the same time.1 In the HER2CLIMB study, capecitabine 1 g/m2 twice daily was administered within 30 minutes after a meal on days 1-14 and trastuzumab 8 mg/kg IV initially, followed by either 6 mg/kg IV or 600 mg by subcutaneous injection was administered on day 1 of each 21-day cycle.1, 11
For use in combination with trastuzumab for the treatment of unresectable or metastatic colorectal cancer in adults, the recommended dosage of tucatinib is 300 mg twice daily.1 Therapy should be continued until disease progression or unacceptable toxicity1
Clinicians should consult the manufacturers' labelings or published protocols for information on the dosage, method of administration, and administration sequence of other antineoplastic agents used in combination regimens.1
Dosage Modification for Toxicity
If adverse reactions occur during tucatinib therapy, temporary interruption of therapy, dosage reduction, and/or permanent discontinuance of the drug may be necessary.1 If dosage reduction is required, the dosage of tucatinib should be reduced as described in Table 1.1
Dose Reduction Level | Recommended Dosage Reductions for Adverse Reactions |
|---|---|
First | 250 mg twice daily |
Second | 200 mg twice daily |
Third | 150 mg twice daily |
Fourth | Permanently discontinue tucatinib |
Table 2 indicates the recommended dosage modification (i.e., temporary interruption of therapy, dosage reduction, discontinuance of therapy) for adverse effects according to severity.1
Adverse Reaction and Severity | Modification |
|---|---|
Diarrhea (Grade 3 without anti-diarrheal treatment) | Initiate or intensify appropriate medical therapy. Hold tucatinib until recovery to ≤ Grade 1, then resume at the same dose level. |
Diarrhea (Grade 3 with anti-diarrheal treatment) | Initiate or intensify appropriate medical therapy. Hold tucatinib until recovery to ≤ Grade 1, then resume at the next lower dose level. |
Diarrhea (Grade 4) | Permanently discontinue |
Hepatotoxicity (Grade 2 bilirubin [>1.5 to 3 × ULN]) | Hold tucatinib until recovery to ≤ Grade 1, then resume at the same dose level. |
Hepatotoxicity (Grade 3 ALT or AST [> 5 to 20 × ULN] OR Grade 3 bilirubin [> 3 to 10 × ULN]) | Hold tucatinib until recovery to ≤ Grade 1, then resume at the next lower dose level. |
Hepatotoxicity (Grade 4 ALT or AST [> 20 × ULN] OR Grade 4 bilirubin [> 10 × ULN]) | Permanently discontinue |
Hepatotoxicity (ALT or AST > 3 × ULN AND Bilirubin > 2 × ULN) | Permanently discontinue |
Other adverse reactions (Grade 3) | Hold tucatinib until recovery to ≤ Grade 1, then resume at the next lower dose level. |
Other adverse reactions (Grade 4) | Permanently discontinue |
Concomitant Use of Drugs Affecting Hepatic Microsomal Enzymes
Concomitant use of tucatinib with potent inhibitors of cytochrome P-450 (CYP) isoenzyme 2C8 should be avoided.1 If concomitant use cannot be avoided, the manufacturer recommends reducing the dosage of tucatinib to 100 mg twice daily.1 If concomitant use of the potent CYP2C8 inhibitor is discontinued, the tucatinib dosage should be returned (after 3 elimination half-lives of the CYP2C8 inhibitor) to the dosage used prior to initiation of the CYP2C8 inhibitor.1
For patients with severe hepatic impairment (Child-Pugh class C), the manufacturer recommends a tucatinib dosage of 200 mg twice daily.1
No dosage adjustment is necessary in patients with mild or moderate hepatic impairment (Child-Pugh class A or B).1
No dosage adjustment is necessary in patients with mild or moderate renal impairment (creatinine clearance 30-89 mL/minute using Cockcroft-Gault formula).1
Because capecitabine is contraindicated in patients with severe renal impairment (creatinine clearance less than 30 mL/minute using Cockcroft-Gault formula), combination therapy with tucatinib, capecitabine, and trastuzumab is not recommended in such patients.1
The manufacturer makes no specific dosage recommendations for geriatric patients.1
None.1
Severe diarrhea associated with dehydration, hypotension, acute kidney injury, and death has been reported in patients receiving tucatinib.1
Antidiarrheal therapy should be administered as clinically indicated if diarrhea occurs during tucatinib therapy.1 Diagnostic tests should be performed as clinically indicated to exclude other causes of diarrhea.1 Temporary interruption, dosage reduction, or permanent discontinuance of tucatinib may be necessary depending on diarrhea severity.1
In the HER2CLIMB study where tucatinib was used in combination with trastuzumab and capecitabine, diarrhea was reported in 81% of patients receiving tucatinib and was grade 3 or 4 in severity in 12 or 0.5% of patients, respectively.1 Death secondary to grade 4 diarrhea occurred in both patients who developed grade 4 diarrhea.1 The median time to initial onset of diarrhea was 12 days and the median time to resolution was 8 days.1 Dosage reduction or discontinuance of tucatinib therapy was necessary because of diarrhea in 6 or 1% of patients, respectively.1 In the HER2CLIMB study, antidiarrheal prophylaxis was not required.1
In the MOUNTAINEER study where tucatinib was used in combination with trastuzumab, diarrhea was reported in 64% of patients, including grade 3 (3.5%), grade 2 (10%), and grade 1 (50%).1
Severe hepatotoxicity has been reported in patients receiving tucatinib.1
In the HER2CLIMB study, elevations in ALT or AST concentration exceeding 5 times the upper limit of normal (ULN) occurred in 8 or 6% of patients receiving tucatinib, respectively.1 In this study, elevations in serum bilirubin concentration exceeding 3 times the ULN occurred in 1.5% of tucatinib-treated patients.1 Dosage reduction or discontinuance of tucatinib therapy was necessary because of hepatotoxicity in 8 or 1.5% of patients, respectively.1
In the MOUNTAINEER study, elevations of ALT or AST concentration exceeding 5 times the ULN occurred in 4.7 or 6% of patients receiving tucatinib, respectively.1 In this study, elevations in serum bilirubin concentration exceeding 3 times the ULN occurrred in 6% of patients.1 Dosage reduction or discontinuation of tucatinib therapy was necessary because of hepatotoxicity in 3.5% and 2.3% of of patients, respectively.1
Liver function tests (i.e., ALT, AST, bilirubin concentrations) should be evaluated prior to initiation of therapy, every 3 weeks thereafter, and as clinically indicated.1 Temporary interruption, dosage reduction, or permanent discontinuance of tucatinib may be necessary depending on the severity of hepatotoxicity.1
Fetal/Neonatal Morbidity and Mortality
There are no adequate and well-controlled studies of tucatinib in pregnant women; however, based on its mechanism of action and animal findings, tucatinib may cause fetal harm.1 Embryofetal toxicity (e.g., increased fetal resorption, abortion, decreased fetal weight) and teratogenicity (e.g., skeletal, visceral, external malformations) have been demonstrated in pregnant animals receiving tucatinib at exposure levels 1.3 times or more the human exposure at the recommended dosage.1
Pregnancy should be avoided during tucatinib therapy.1 The manufacturer states that a pregnancy test should be performed prior to initiation of tucatinib therapy in females of reproductive potential and that such women should be advised to use effective contraceptive methods while receiving tucatinib therapy and for at least 1 week after the last dose of the drug.1 In addition, men with such female partners should use effective contraceptive methods while receiving tucatinib and for at least 1 week after the last dose of the drug.1 Patients should be apprised of the potential hazard to the fetus if tucatinib is used during pregnancy.1
Results of animal studies suggest that tucatinib may impair male and female fertility.1
Tucatinib may cause fetal harm if administered to pregnant women based on its mechanism of action and animal findings.1
It is not known whether tucatinib or its metabolites are distributed into human milk.1 The effects of the drug on breast-fed infants or on the production of milk also are unknown.1
Because of the potential for serious adverse reactions to tucatinib in breast-fed infants, women should be advised not to breast-feed while receiving the drug and for at least 1 week after the last dose.1
Safety and efficacy of tucatinib have not been established in pediatric patients.1
In the HER2CLIMB study, 26% of patients receiving tucatinib were 65 years of age or older, while 2.5% were 75 years of age or older.1 No overall differences in efficacy were observed between geriatric patients and younger adults.1 Patients 65 years of age or older had a higher incidence of serious adverse reactions (e.g., diarrhea, vomiting, nausea) compared with younger adults (34 or 24%, respectively).1 In the MOUNTAINEER study, 12 patients were 65 years of age or older; however, there were too few patients in this population to assess differences in effectiveness or safety in this study.1
Following administration of a single 300-mg dose of tucatinib, area under the plasma concentration-time curve (AUC) of tucatinib in individuals with mild or moderate hepatic impairment (Child-Pugh class A or B) was similar to that in individuals with normal hepatic function, but was increased by 1.6-fold in those with severe hepatic impairment (Child-Pugh class C); therefore, the manufacturer recommends a tucatinib dosage of 200 mg twice daily in patients with severe hepatic impairment.1, 16
In a population pharmacokinetic analysis, mild or moderate renal impairment did not have clinically important effects on the pharmacokinetics of tucatinib; no dosage adjustment is necessary in patients with mild or moderate renal impairment.1, 16
The pharmacokinetic profile of tucatinib has not been established in patients with severe renal impairment.1
Adverse effects reported in at least 20% of patients with metastatic breast cancer receiving tucatinib in combination with trastuzumab and capecitabine include diarrhea, palmar-plantar erythrodysesthesia, nausea, hepatotoxicity, vomiting, stomatitis, decreased appetite, anemia, and rash.1
Adverse effects reported in at least 20% of patients with unresectable or metastatic colorectal cancer receiving tucatinib in combination with trastuzumab include diarrhea, fatigue, rash, nausea, abdominal pain, infusion related reactions, and pyrexia.1
Tucatinib has been shown to increase serum creatinine concentrations.1 Tucatinib decreases tubular secretion of creatinine by inhibiting renal organic cation transporter (OCT) 2 and multidrug and toxin extrusion transporter (MATE) 1.1 The mean increase in serum creatinine was 32%, reported within the initial 21 days of tucatinib therapy.1 Elevated concentrations of serum creatinine persisted during therapy and reversed in most patients following discontinuance of therapy.1 The manufacturer states that assessment of alternative markers for renal function may be necessary if elevated serum creatinine concentrations persist.1
Tucatinib is metabolized principally by cytochrome P-450 (CYP) isoenzyme 2C8 and, to a lesser extent, by CYP3A.1 In vitro, tucatinib demonstrates reversible inhibition of CYP isoenzymes 2C8 and 3A, and time-dependent inhibition of CYP3A.1 In vitro, the drug is not an inhibitor of CYP isoenzymes 1A2, 2B6, 2C9, 2C19, and 2D6, or uridine diphosphate-glucuronosyltransferase (UGT) 1A1.1
In vitro studies indicate that tucatinib is a substrate of P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP), but is not a substrate of organic anion transporter (OAT) 1, OAT3, organic cation transporter (OCT) 1, OCT3, organic anion transporting polypeptide (OATP) 1B1, OATP1B3, multidrug and toxin extrusion (MATE) 1, MATE2K, or bile salt export pump (BSEP).1
Drugs Affecting Hepatic Microsomal Enzymes
Concomitant use of tucatinib with potent inhibitors of CYP2C8 may result in increased systemic exposure to tucatinib and an increased incidence of adverse effects.1 Concomitant administration of the potent CYP2C8 inhibitor gemfibrozil (600 mg twice daily) with tucatinib (single 300-mg dose) increased the area under the concentration-time curve (AUC) and peak plasma concentration of tucatinib by 3- and 1.6-fold, respectively.1, 16
Concomitant use of tucatinib with potent inhibitors of CYP2C8 should be avoided.1 If concomitant use of a potent CYP2C8 inhibitor cannot be avoided, the manufacturer recommends reducing the dosage of tucatinib to 100 mg twice daily.1 If concomitant use of the potent CYP2C8 inhibitor is discontinued, the tucatinib dosage should be returned (after 3 elimination half-lives of the CYP2C8 inhibitor) to the dosage used prior to initiation of the CYP2C8 inhibitor.1
If concomitant therapy with a moderate CYP2C8 inhibitor is required, patients should be monitored closely for signs of tucatinib toxicity.1
Concomitant use of tucatinib with potent CYP3A or moderate CYP2C8 inducers may result in decreased systemic exposure to tucatinib and reduced tucatinib efficacy.1 Concomitant administration of the potent CYP3A and moderate CYP2C8 inducer rifampin (600 mg once daily) with tucatinib (single 300-mg dose) decreased AUC and peak plasma concentration of tucatinib by 48 and 37%, respectively.1, 16
Concomitant use of tucatinib with potent CYP3A or moderate CYP2C8 inducers should be avoided.1
When the potent CYP3A inhibitor itraconazole (200 mg twice daily) was administered concomitantly with tucatinib (single 300-mg dose), both AUC and peak plasma concentration of tucatinib increased by 1.3-fold.1
Drugs Metabolized by Hepatic Microsomal Enzymes
Concomitant use of tucatinib with CYP3A substrates may result in increased systemic exposure to the CYP3A substrate and increased incidence of adverse effects of the substrate drug.1 When the CYP3A substrate midazolam (single 2-mg dose) was administered concomitantly with tucatinib (300 mg twice daily), AUC and peak plasma concentration of midazolam increased 5.7- and 3-fold, respectively.1, 16
Concomitant use of tucatinib with CYP3A substrates that have a narrow therapeutic index should be avoided.1 If concomitant use of CYP3A substrates that have a narrow therapeutic index cannot be avoided, the dosage of the CYP3A substrate should be adjusted as appropriate.1
Drugs Affected by Transport Systems
Concomitant use of tucatinib with P-gp substrates may result in increased systemic exposure of the P-gp substrate and increased incidence of adverse effects of the substrate drug.1 When the P-gp substrate digoxin (single 0.5-mg dose) was administered concomitantly with tucatinib (300 mg twice daily), AUC and peak plasma concentrations of digoxin increased 1.5- and 2.4-fold, respectively.1
If concomitant use of P-gp substrates that have a narrow therapeutic index is required, the dosage of the P-gp substrate should be adjusted as appropriate.1
Substrates of MATE1, MATE2K, and OCT2
When a single 850-mg dose of metformin hydrochloride (a substrate of MATE1, MATE2K, and OCT2) was administered concomitantly with tucatinib (300 mg twice daily for 7 days), AUC and peak plasma concentrations of metformin increased 1.4- and 1.1-fold, respectively.1, 16 Tucatinib reduced the renal clearance of metformin without any effect on glomerular filtration rate (GFR).1
Concomitant administration of tucatinib and the proton-pump inhibitor omeprazole did not affect the pharmacokinetics of tucatinib.1
Concomitant administration of tucatinib and tolbutamide (sensitive CYP2C9 substrate) did not have a clinically important effect on the pharmacokinetics of tucatinib.1
Tucatinib, a highly selective, reversible tyrosine kinase inhibitor of human epidermal growth factor receptor type 2 (HER2), is an antineoplastic agent.1, 9, 14, 15, 16, 18 In vitro, the drug has been shown to inhibit phosphorylation of HER2 and HER3 resulting in inhibition of downstream signaling of the mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K/Akt) pathways.1 In vivo, tucatinib has demonstrated inhibition of cellular proliferation of HER2-expressing tumors.1 The combination of tucatinib with trastuzumab demonstrated increased antitumor activity compared with either drug alone.1, 9, 12, 16
In cell-based assays, tucatinib has demonstrated 500-fold greater selectivity for HER2 than for epidermal growth factor receptor (EGFR), thereby potentially reducing the incidence of adverse effects associated with EGFR inhibition, such as adverse GI and dermatologic effects.14, 15, 18
Area under the serum concentration-time curve (AUC) and peak plasma concentrations of tucatinib are dose proportional over a dosage range of 50-300 mg.1 Following oral administration of tucatinib, peak plasma concentrations of the drug are achieved in a median of approximately 2 hours (range 1-4 hours).1 With twice-daily administration, steady-state concentrations of the drug are achieved in approximately 4 days and the accumulation based on geometric mean AUC accumulation ratios ranged from 2-2.5-fold.1 Administration of tucatinib (single 300-mg dose) with a high-fat meal decreased the rate of absorption (time to peak concentrations delayed by 2.5 hours) and increased the mean AUC by 1.5-fold, but did not substantially affect peak plasma concentration; however, these changes are not considered clinically meaningful.1, 16 Tucatinib is 97.1% bound to plasma proteins at clinically relevant concentrations.1 Tucatinib is metabolized principally by cytochrome P-450 (CYP) isoenzyme 2C8 and, to a lesser extent, by CYP3A.1 Following oral administration of a single radiolabeled dose of tucatinib, approximately 86% of the radioactivity was recovered in feces (16% of the dose as unchanged drug) and 4.1% was recovered in urine.1 The mean elimination half-life of tucatinib is 11.9 hours in patients with metastatic breast cancer and 16.4 hours in patients with metastatic colorectal cancer.1 Systemic exposure of tucatinib is not affected by age, serum albumin concentration (2.5-5.2 g/dL), body weight (41-138 kg), and race (white, Black, or Asian).1, 12
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. For further information on the handling of antineoplastic agents, see the ASHP Guidelines on Handling Hazardous Drugs at [Web].
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.
Tucatinib is available only from a designated specialty pharmacy.17 The manufacturer should be contacted for additional information.17
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Oral | Tablets, film-coated | 50 mg | Seattle Genetics | |
150 mg | Tukysa® | Seattle Genetics |
AHFS® Drug Information. © Copyright, 1959-2026, Selected Revisions September 28, 2023. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, MD 20814.
1. Seattle Genetics Inc. Tukysa® (tucatinib) tablets prescribing information. Bothell, WA; 2023 Jan.
6. Food and Drug Administration. FDA Application: Search orphan drug designations and approvals. Silver Spring, MD. From FDA web site. [Web]
7. Bredin P, Walshe JM, Denduluri N. Systemic therapy for metastatic HER2-positive breast cancer. Semin Oncol . 2020; 47:259-269. [PubMed 32896428]
8. Tarantino P, Prat A, Cortes J et al. Third-line treatment of HER2-positive advanced breast cancer: From no standard to a Pandora's box. Biochim Biophys Acta Rev Cancer . 2021; 1875:188487. [PubMed 33259892]
9. Shah M, Wedam S, Cheng J et al. FDA Approval Summary: Tucatinib for the Treatment of Patients with Advanced or Metastatic HER2-positive Breast Cancer. Clin Cancer Res . 2021; 27:1220-1226. [PubMed 33055172]
10. Cesca MG, Vian L, Cristóvão-Ferreira S et al. HER2-positive advanced breast cancer treatment in 2020. Cancer Treat Rev . 2020; 88:102033. [PubMed 32534233]
11. Murthy R, Borges VF, Conlin A et al. Tucatinib with capecitabine and trastuzumab in advanced HER2-positive metastatic breast cancer with and without brain metastases: a non-randomised, open-label, phase 1b study. Lancet Oncol . 2018; 19:880-888. [PubMed 29804905]
12. Lee A. Tucatinib: First Approval. Drugs . 2020; 80:1033-1038. [PubMed 32548668]
14. Dormann C. Metastatic Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer: Current Treatment Standards and Future Perspectives. Breast Care (Basel) . 2020; 15:570-578. [PubMed 33447230]
15. Kunte S, Abraham J, Montero AJ. Novel HER2-targeted therapies for HER2-positive metastatic breast cancer. Cancer . 2020; 126:4278-4288. [PubMed 32721042]
16. Food and Drug Administration. Center for Drug Evaluation and Research. Application number: 213411Orig1s000: Multi-discipline review. From FDA website. [Web]
17. Seagen. Seagen Secure: Access. Advocates. Answers. From the Tukysa® website. Accessed 2021 Mar 25. [Web]
18. Moulder SL, Borges VF, Baetz T et al. Phase I Study of ONT-380, a HER2 Inhibitor, in Patients with HER2+-Advanced Solid Tumors, with an Expansion Cohort in HER2+ Metastatic Breast Cancer (MBC). Clin Cancer Res . 2017; 23:3529-3536. [PubMed 28053022]
19. Lin NU, Borges V, Anders C et al. Intracranial Efficacy and Survival With Tucatinib Plus Trastuzumab and Capecitabine for Previously Treated HER2-Positive Breast Cancer With Brain Metastases in the HER2CLIMB Trial. J Clin Oncol . 2020; 38:2610-2619. [PubMed 32468955]
20. Murthy R, Borges VF, Conlin A et al. Tucatinib with capecitabine and trastuzumab in advanced HER2-positive metastatic breast cancer with and without brain metastases: a non-randomised, open-label, phase 1b study. Lancet Oncol . 2018; 19:880-888. [PubMed 29804905]
21. Institute for Safe Medication Practices (ISMP). ISMP list of high-alert medications in acute care settings. ISMP; 2018. [Web]
22. Strickler JH, Cercek A, Siena S et al. Tucatinib plus trastuzumab for chemotherapy-refractory, HER2-positive, RAS wild-type unresectable or metastatic colorectal cancer (MOUNTAINEER): a multicentre, open-label, phase 2 study. Lancet Oncol. 2023 May;24(5):496-508. doi: 10.1016/S1470-2045(23)00150-X.