Dacomitinib, an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, is an antineoplastic agent.1, 6, 13, 16
Dacomitinib is used for the first-line treatment of metastatic non-small cell lung cancer (NSCLC) in patients whose tumors harbor epidermal growth factor receptor ( EGFR ) exon 19 deletions (del19) or exon 21 (L858R) substitution mutations as detected by an FDA-approved diagnostic test (e.g., therascreen® EGFR RGQ PCR Kit, cobas® EGFR Mutation Test v2).1, 2, 26, 29 Information on FDA-approved companion diagnostic tests for the detection of EGFR mutations in NSCLC is available at [Web].1 Dacomitinib has been designated an orphan drug by FDA for use in this condition.3 Safety and efficacy of dacomitinib in this use are primarily supported by a Phase 3, randomized, controlled trial demonstrating progression-free and overall survival benefit in adults with previously untreated EGFR mutation-positive metastatic NSCLC receiving dacomitinib compared with patients receiving gefitinib.1, 27, 29 Dacomitinib is one of several generally recommended therapies for adults with previously-untreated NSCLC with EGFR- activating mutations for whom osimertinib is not an option.35, 36
The current indication for dacomitinib in the treatment of metastatic NSCLC is based principally on the results of a randomized, multinational, open-label phase 3 study (ARCHER-1050) in adults with newly diagnosed locally advanced or metastatic NSCLC.1, 2 Patients who received systemic therapy in the adjuvant or neoadjuvant setting were enrolled in this study if disease progression occurred at least 12 months following adjuvant or neoadjuvant therapy.1, 2 In this study, 452 patients were randomized (stratified by ethnicity and type of EGFR mutation) in a 1:1 ratio to receive either dacomitinib (45 mg orally once daily) or gefitinib (250 mg orally once daily) until disease progression or unacceptable toxicity occurred.1, 2 The primary measure of efficacy was progression-free survival (as evaluated by a blinded independent central review committee according to Response Evaluation Criteria in Solid Tumors [RECIST]).1, 2
The median age of patients was 62 years (range: 28-87 years); most patients (92%) had metastatic disease, 77% were of Asian ancestry, 70% had a baseline Eastern Cooperative Oncology Group (ECOG) performance status of 1, 64% had never smoked, and 1% had received prior adjuvant or neoadjuvant therapy.1 All patients enrolled in the study were required to have evidence of an EGFR mutation (confirmed by the therascreen® EGFR RGQ PCR Kit); 59% of patients had exon 19 deletions and 41% had exon 21 (L858R) substitution mutations.1, 2
At a median follow-up of 22.1 months, patients receiving dacomitinib had a longer median progression-free survival compared with patients receiving gefitinib (14.7 versus 9.2 months; hazard ratio [HR], 0.59).1, 2 Although objective response rates were similar between both treatment groups, patients receiving dacomitinib had a longer median duration of response compared with those receiving gefitinib (14.8 versus 8.3 months, respectively).1, 2 At a median follow-up of approximately 31 months, median overall survival was prolonged in patients receiving dacomitinib compared with those receiving gefitinib (34.1 months versus 26.8 months; HR, 0.76).27 Results of a subgroup analysis (based on age, sex, ECOG performance status, race, smoking status, EGFR mutation) suggested that the effect of dacomitinib on progression-free survival was evident across all subgroups; however, subgroup analysis according to race (Asian versus non-Asian) suggested that dacomitinib had a greater effect on progression-free survival in Asian patients relative to non-Asian patients (HR, 0.51 and 0.89, respectively).2 Results of an updated analysis demonstrated maintained benefit of dacomitinib over gefitinib on overall survival after a median follow-up of 47.9 months.29
EGFR -activating mutations are present in approximately 15-22% of NSCLC cases in North America and Europe and are present in up to 30-50% of cases in patients of East Asian descent.5, 13 The majority of EGFR mutations are exon 19 deletions and an L858R substitution in exon 21, which together account for about 90% of EGFR mutations in patients with NSCLC.4, 12 EGFR mutations are identified in a large proportion of NSCLC cases in nonsmokers (49.3%), female patients (43.7%), and those with adenocarcinoma histology (38%).55
The American Society of Clinical Oncology (ASCO) and Ontario Health (OH; formerly known as Cancer Care Ontario) 2021 joint guideline specifically addresses treatment of stage IV NSCLC harboring driver alterations such as EGFR mutations.35 For patients with previously untreated stage IV NSCLC harboring sensitizing EGFR mutations (L858R/exon 19 deletion) with or without a concomitant T790M mutation and a performance status of 0-2, ASCO/OH states that osimertinib should be offered.35 In otherwise similar cases without a concomitant T790M mutation for whom osimertinib is not available, gefitinib in combination with a platinum and pemetrexed or dacomitinib monotherapy may be used.35 When osimertinib and dacomitinib are not available and gefitinib in combination with carboplatin and pemetrexed is not an option in such cases, afatinib monotherapy or the combination of erlotinib with a vascular endothelial growth factor inhibitor+ (e.g., bevacizumab, ramucirumab) may be used.35 When the previously-mentioned therapies are not available in such cases, patients may receive monotherapy with gefitinib or erlotinib.35 For patients with previously untreated stage IV NSCLC harboring sensitizing EGFR mutations (L858R/exon 19 deletion) and a performance status of 3, monotherapy with an EGFR tyrosine kinase inhibitor may be offered based on access and toxicity.35 For patients with an activating EGFR mutation other than exon 20 insertion mutations, T790M, L858R, or exon 19 deletion (e.g., G719X, L861Q, and S768I), and a performance status of 0-2, who have not received systemic therapy, clinicians may offer afatinib monotherapy, osimertinib, or standard treatment based on the ASCO/OH nondriver mutation guideline.35 The 2022 ASCO living guideline for treatment of NSCLC with driver alterations reaffirms these recommendations.36
Dacomitinib is administered orally once daily at approximately the same time each day; the drug can be taken without regard to meals.1
If a dose of dacomitinib is missed or vomited, the prescribed dose should be taken at the next scheduled time; an additional dose should not be administered to replace the missed dose.1
Store at 20-25°C (excursions permitted between 15-30°C).1
For the first-line treatment of metastatic NSCLC in patients whose tumors harbor EGFR del19 or L858R substitution mutations, the recommended dosage of dacomitinib in adults is 45 mg once daily.1 Therapy should be continued until disease progression or unacceptable toxicity occurs.1 In the principal efficacy study (ARCHER-1050), dacomitinib therapy was continued for a median duration of 15 months.1
Dosage Modification for Toxicity
Dosage interruption and/or reduction or discontinuance of dacomitinib therapy may be necessary based on type and severity of adverse reactions.1 If dosage reduction from 45 mg once daily is necessary, the dosage should be reduced to 30 mg once daily.1 If the toxicity recurs at a dosage of 30 mg once daily, the dosage should be further reduced to 15 mg once daily.1
If interstitial lung disease (any grade) occurs, permanently discontinue dacomitinib therapy.1
If grade 2 diarrhea occurs, withhold dacomitinib therapy.1 When the toxicity improves to grade 1 or less, resume dacomitinib therapy at the same dosage.1 If grade 2 diarrhea recurs, withhold dacomitinib therapy; resume therapy at a reduced dosage when the toxicity improves to grade 1 or less.1
If grade 3 or 4 diarrhea occurs, withhold dacomitinib therapy.1 When the toxicity improves to grade 1 or less, resume dacomitinib therapy at a reduced dosage.1
If grade 2 dermatologic reactions occur and persist during dacomitinib therapy, withhold therapy.1 When the toxicity improves to grade 1 or less, resume dacomitinib therapy at the same dosage.1 If grade 2 dermatologic reactions recur and persist during dacomitinib therapy, withhold the drug; resume therapy at a reduced dosage when the toxicity improves to grade 1 or less.1
If grade 3 or 4 dermatologic reactions occur, withhold dacomitinib therapy.1 When the toxicity improves to grade 1 or less, resume dacomitinib therapy at a reduced dosage.1
If any other grade 3 or 4 adverse reaction occurs, interrupt dacomitinib therapy.1 When the toxicity improves to grade 2 or less, resume dacomitinib at a reduced dosage.1
Dosage Modification for Acid-reducing Agents
Avoid concomitant use of dacomitinib and proton-pump inhibitors.1 If therapy with an acid suppressive agent is necessary in a patient receiving dacomitinib, use a histamine H2-receptor antagonist or locally-acting antacid instead of a proton-pump inhibitor.1 Administer dacomitinib ≥6 hours before or 10 hours after administration of a histamine H2-receptor antagonist.1
No dosage adjustment is necessary in patients with mild, moderate, or severe impairment (Child-Pugh class A, B, or C).1
No dosage adjustment is necessary in patients with mild or moderate renal impairment (creatinine clearance 30-89 mL/minute).1 There are limited data in patients with severe renal impairment (creatinine clearance <30 mL/minute); the manufacturer provides no specific dosage recommendations for such patients.1
The manufacturer makes no specific dosage recommendations for geriatric patients.1
None.1
Interstitial lung disease (ILD) or pneumonitis, sometimes fatal, has been reported in patients receiving dacomitinib.1, 4 In clinical trials, severe or fatal ILD or pneumonitis occurred in 0.5% of 394 patients receiving dacomitinib; 0.3% of cases were fatal.1 In the principal efficacy study in patients with previously untreated metastatic non-small cell lung cancer (NSCLC) (ARCHER-1050), ILD occurred in 1.3% of patients receiving dacomitinib, of which 1 case was fatal.1, 4 Temporary interruption or discontinuance of dacomitinib therapy was necessary due to ILD in 1 or 1.8%, respectively, of patients receiving the drug.1, 4
Monitor patients receiving dacomitinib for manifestations of ILD or pneumonitis.1 In patients who present with worsening of respiratory symptoms (e.g., dyspnea, cough, fever), withhold dacomitinib therapy and promptly evaluate the patient.1 If a diagnosis of ILD is confirmed, permanently discontinue dacomitinib.1
Diarrhea. sometimes fatal, has been reported frequently in patients receiving dacomitinib.1 In clinical trials, diarrhea was reported in 86% of 394 patients receiving dacomitinib; grade 3 or 4 diarrhea occurred in 11% of patients and 0.3% of cases were fatal.1 In the ARCHER-1050 study, diarrhea was reported in 87% of patients receiving dacomitinib; grade 3 or 4 diarrhea occurred in 8% of these patients.1 Temporary interruption, dosage reduction, or discontinuance of dacomitinib therapy was necessary due to diarrhea in 10, 8, or 0.9%, respectively, of patients receiving the drug.1
Although the mechanism for development of diarrhea has not been fully determined, an increased incidence and greater severity of diarrhea have been observed with second-generation pan-human epidermal growth factor receptor (pan-HER) inhibitors (e.g., dacomitinib, afatinib) compared with single-target tyrosine kinase inhibitors selective for epidermal growth factor receptor (EGFR) (e.g., erlotinib, gefitinib); therefore, it has been suggested that other members of the HER tyrosine kinase family may have an essential role in the development of diarrhea.28
If diarrhea occurs, promptly initiate appropriate therapy (e.g., loperamide, diphenoxylate hydrochloride with atropine sulfate).1 Dosage modification of dacomitinib therapy may be necessary depending on the severity of the diarrhea.1
Dermatologic adverse reactions have been reported frequently in patients receiving dacomitinib.1 In clinical trials, rash or exfoliative skin reactions were reported in 78 or 7% of 394 patients receiving dacomitinib, respectively; grade 3 or 4 rash or exfoliative skin reactions were reported in 21 or 1.8%, respectively, of patients receiving dacomitinib.1 In the ARCHER-1050 study, rash was reported in 69% of patients receiving dacomitinib; grade 3 or 4 rash occurred in 23% of these patients.1 Temporary interruption, dosage reduction, or discontinuance of dacomitinib therapy was necessary due to rash in 23, 29, or 2.6%, respectively, of patients receiving the drug.1 Paronychia also was reported in 64% of patients receiving dacomitinib in the ARCHER-1050 study; temporary interruption or dosage reduction of dacomitinib therapy was necessary due to paronychia in 13 or 17%, respectively, of patients receiving the drug.1
The incidence and severity of rash and exfoliative skin reactions may increase with sun exposure.1 Advise patients to routinely moisturize their skin and limit exposure to sunlight upon initiation of dacomitinib and during treatment.1 Some clinicians state that prophylaxis with a systemic anti-infective may be helpful in some cases.22 Dosage modification of dacomitinib therapy may be necessary if persistent grade 2 or more severe rash occurs; oral anti-infective therapy also should be initiated.1 If grade 1 rash occurs, topical anti-infective and steroid therapy should be initiated.1
Fetal/Neonatal Morbidity and Mortality
Dacomitinib may cause fetal harm in humans based on its mechanism of action and findings from animal studies.1 There are no available data on dacomitinib use in pregnant women; however, the drug has been shown to be embryotoxic and fetotoxic in animals.1
Advise pregnant women and females of reproductive potential of the potential risk to the fetus.1 Confirm pregnancy status in females of reproductive potential prior to initiation of dacomitinib.1 Advise females of reproductive potential to use effective contraception while receiving dacomitinib and for ≥17 days after the last dose.1
Dacomitinib may cause fetal harm if administered to pregnant women based on its mechanism of action and findings from animal studies.1
In animals, disruption or blockade of signaling of the EGFR pathway has been associated with preimplantation loss, embryo-fetal loss during various stages of gestation, postnatal death, developmental anomalies, and visceral abnormalities.1 Embryo-fetal toxicity (e.g., decreased fetal body weight, postimplantation loss) and maternal toxicity have been demonstrated in animals receiving dacomitinib at exposure levels equivalent to approximately 1.2 times the human exposure at the recommended dosage.1
It is not known whether dacomitinib or its metabolites distribute into human milk; the effects of the drug on breast-fed infants or on the production of breast milk are also unknown.1 Because of the potential for adverse reactions to dacomitinib in breast-fed infants, females should be advised not to breast-feed while receiving the drug and for ≥17 days after the last dose.1
Females and Males of Reproductive Potential
Pregnancy testing is recommended in females of reproductive potential before starting dacomitinib.1 Due to risk of embryo-fetal harm, females of reproductive potential should use an effective method of contraception while taking dacomitinib and for ≥17 days after the last dose.1
Safety and efficacy of dacomitinib have not been established in pediatric patients.1
Across 5 clinical studies of patients (N=394) receiving dacomitinib 45 mg once daily, 40% were ≥65 years of age or older.1 Exploratory analyses suggest a higher incidence of grade 3 or 4 adverse reactions, more frequent dosage interruptions, and more discontinuations of dacomitinib due to adverse reactions in patients ≥65 years of age compared to those <65 years of age.1
No clinically significant differences in the pharmacokinetics of dacomitinib were observed in patients with mild, moderate, or severe hepatic impairment (Child-Pugh class A, B or C).1
Population pharmacokinetic analyses suggest that there is no clinically important difference in the pharmacokinetics of dacomitinib in individuals with mild or moderate renal impairment (creatinine clearance 30 to <90 mL/minute) compared with individuals with normal renal function (creatinine clearance ≥90 mL/minute).1, 4
The pharmacokinetic profile of dacomitinib has not been established in patients with severe renal impairment (creatinine clearance <30 mL/minute) and in those receiving dialysis.1, 4
Adverse effects reported in >20% of patients include diarrhea, rash, paronychia, stomatitis, decreased appetite, dry skin, decreased weight, alopecia, cough, and pruritus.1
Dacomitinib is principally metabolized by oxidation and glutathione conjugation.1 Dacomitinib also is metabolized by cytochrome P-450 (CYP) isoenzyme 2D6 to form its major metabolite, O -desmethyldacomitinib, and by CYP3A4 to form other minor oxidative metabolites.1, 4
In vitro studies indicate that dacomitinib is a potent inhibitor and substrate of CYP2D6;4 dacomitinib does not induce CYP isoenzymes 1A2, 2B6, or 3A4.1 In vitro studies show that dacomitinib and its principal active metabolite do not inhibit CYP isoenzymes 1A2, 2B6, 2C8, 2C9, 2C19, or 3A4/5.1 Dacomitinib also is an inhibitor of uridine diphosphate-glucuronosyltransferase (UGT) 1A1, but does not inhibit UGT1A4, 1A6, 1A9, 2B7, or 2B15.1
In vitro studies indicate that dacomitinib is a substrate of P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP).1 In vitro, dacomitinib is an inhibitor of P-gp, BCRP, and organic cation transporter (OCT) 1, but does not inhibit organic anion transporter (OAT) 1, OAT3, OCT2, organic anion transport protein (OATP) 1B1, or OATP1B3.1
Drugs Affecting Hepatic Microsomal Enzymes
Although dacomitinib is a substrate of CYP2D6, CYP2D6-mediated mechanisms play a minor role in the overall metabolism of the drug.4 Concomitant use of dacomitinib (single 45-mg dose) with the potent CYP2D6 inhibitor paroxetine (30 mg once daily) did not result in clinically important changes in AUC of the total active forms of the drug (i.e., dacomitinib plus O -desmethyldacomitinib);1, 4 no initial dosage adjustment is necessary.4
Drugs Metabolized by Hepatic Microsomal Enzymes
Concomitant use of dacomitinib with drugs that are metabolized by CYP2D6 may result in increased exposure of the substrate drug and an increased incidence of drug toxicity.1 When the CYP2D6 substrate dextromethorphan (single 30-mg dose) was administered concomitantly with dacomitinib (single 45-mg dose), the peak plasma concentration and AUC of dextromethorphan were increased by 9.7- and 9.6-fold, respectively.1, 4 Avoid concomitant use of dacomitinib with CYP2D6 substrates where minimal increases in the substrate concentration may lead to serious or life-threatening toxicities.1
Drugs Affecting Gastric Acidity
The solubility of dacomitinib decreases with increasing pH;4 therefore, drugs that reduce gastric acidity such as proton-pump inhibitors, antacids, and histamine H2-receptor antagonists potentially can decrease plasma concentrations of dacomitinib and thereby reduce its efficacy.1 Avoid concomitant use of dacomitinib and proton-pump inhibitors.1 If therapy with an acid suppressive agent is necessary in a patient receiving dacomitinib, use a histamine H2-receptor antagonist (e.g., cimetidine, famotidine, nizatidine, ranitidine) or an antacid (e.g., magnesium oxide)4 rather than a proton-pump inhibitor.1
When dacomitinib (single 45-mg dose) was administered concomitantly with the proton-pump inhibitor rabeprazole (40 mg once daily for 7 days) in healthy individuals, the AUC and peak plasma concentration of dacomitinib were decreased by 39 and 51%, respectively.1, 4
Avoid concomitant use of dacomitinib and proton-pump inhibitors.1
Histamine H2-receptor Antagonists
No formal drug interaction studies have been performed to date;1 however, if concomitant use of dacomitinib and a histamine H2-receptor antagonist is necessary, administer dacomitinib ≥6 hours prior to or 10 hours following administration of the histamine H2-receptor antagonist.1
Concomitant use of dacomitinib (single 45-mg dose) with magnesium oxide (single 1.6-g dose) did not result in clinically important changes in AUC or peak plasma concentrations of dacomitinib.1, 4
Dacomitinib, a selective and irreversible inhibitor of epidermal growth factor receptor (EGFR/human epidermal growth factor receptor type 1 [HER1]/ErbB1), HER2/ErbB2, HER4/ErbB4, and mutated EGFR (e.g., exon 19 deletion [del19], exon 21 substitution [L858R]) tyrosine kinases, is an antineoplastic agent.1, 6, 13, 16 EGFR is expressed on the cell surface of many cancer cells, as well as many normal cells;15 activation of EGFR tyrosine kinase is thought to initiate a cascade of intracellular signaling events leading to cell proliferation and influencing processes critical to cell survival and tumor progression (e.g., angiogenesis, apoptosis, metastasis).12, 13, 14 Some EGFR-activating mutations, such as del19 and L858R, contribute to increased cell proliferation and survival in non-small cell lung cancer (NSCLC) cells harboring these mutations.15
Although first-generation (reversible) EGFR tyrosine kinase inhibitors (e.g., erlotinib, gefitinib) have demonstrated improved outcomes in patients with NSCLC harboring EGFR mutations (e.g., del19, L858R substitution), secondary resistance to these agents eventually develops following 9-13 months of treatment.9, 10 Clinical resistance to first-generation EGFR tyrosine kinase inhibitors has been attributed to several mechanisms, but development of the secondary T790M mutation in exon 20 appears to be the most common, occurring in 50-60% of patients who develop this resistance.7, 8, 9, 10, 11, 21, 24 This mutation results in production of a bulky methionine side chain in the receptor kinase domain of EGFR that is thought to sterically hinder the binding of first-generation EGFR tyrosine kinase inhibitors to EGFR.8, 9, 17, 21, 24, 25 It has been suggested that second-generation EGFR tyrosine kinase inhibitors (e.g., dacomitinib, afatinib) may theoretically delay or prevent the emergence of secondary resistance through their irreversible inhibition of EGFR, more complete blockade of the EGFR signaling pathway (i.e., inhibition of EGFR as well as HER2/ErbB2 and HER4/ErbB4), and inhibitory effects against tumors harboring the T790M mutation.7, 8, 9, 17, 18, 19, 20, 21, 24 Dacomitinib has demonstrated dose-dependent inhibition of phosphorylation of wild-type EGFR and HER2 and tumor growth in xenograft models of human NSCLC or ovarian cancer cell lines that harbored HER2 or EGFR (i.e., del19, L858R, T790M) mutations in mice.1, 4, 21 Dacomitinib also has demonstrated antitumor activity in xenograft models of human glioblastoma cells driven by EGFR gene amplifications, including EGFR variant III (EGFRvIII, EGFR exon 2-7 deletion [del2-7]), in mice.1, 4, 23 In vitro, dacomitinib also has been shown to inhibit DDR1, DDR2, EPHA6, LCK, and MNK1 at clinically relevant concentrations.1
Based on dose-exposure safety relationships, higher dacomitinib exposures at the recommended dacomitinib dosage have been associated with an increased incidence of grade 3 or greater adverse effects, particularly dermatologic toxicities (e.g., rash, dermatitis acneiform) and diarrhea.1, 4 Maximum concentrations of dacomitinib had no large effect on QT interval corrected for rate (QTc).1 Dacomitinib exhibits dose-proportional pharmacokinetics over a dosage range of 2-60 mg once daily.1 Steady-state concentrations of dacomitinib are achieved within 14 days of repeated dosing and the mean accumulation ratio is 5.7.1 Following oral administration of a single dose of dacomitinib 45 mg, the median time to peak plasma concentrations is approximately 6 hours (range: 2-24 hours); the mean absolute bioavailability of dacomitinib is 80%.1 Administration with a high-fat, high-calorie meal did not substantially alter the pharmacokinetics of dacomitinib.1 Dacomitinib is approximately 98% bound to plasma proteins.1 Dacomitinib is principally metabolized by oxidation and glutathione conjugation.1, 4 Cytochrome P-450 (CYP) isoenzyme 2D6 metabolizes dacomitinib to its major metabolite, O-desmethyldacomitinib, which has similar activity inhibiting EGFR tyrosine kinase as dacomitinib in vitro.1, 4 Pharmacokinetics of dacomitinib are not substantially different between poor and extensive metabolizers of CYP2D6.4 O-desmethyldacomitinib accounts for 7.4-19% of the total trough concentrations at steady state.1, 4 The mean terminal half-lives of dacomitinib and O-desmethyldacomitinib are 70.3 and 72.8 hours, respectively.1, 4 Following oral administration of a radiolabeled dose of dacomitinib, 79% of the dose is recovered in feces (approximately 20% of the dose as unchanged drug) and 3% is recovered in urine (<1% of the dose as unchanged drug).1, 4
Analysis of population pharmacokinetic data indicates that age (range: 20-92 years), body weight, gender, race (Asian versus non-Asian), EGFR mutation status, and baseline albumin concentrations have no clinically important effects on clearance of dacomitinib.4
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.
Dacomitinib is available through specialty pharmacies.37 Clinicians may consult the Vizimpro® website for specific information regarding distribution of the drug:[Web].37
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Oral | Tablets, film-coated | 15 mg | Vizimpro® | |
30 mg | Vizimpro® | Pfizer | ||
45 mg | Vizimpro® | Pfizer |
AHFS® Drug Information. © Copyright, 1959-2025, Selected Revisions August 28, 2023. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, MD 20814.
1. Pfizer Labs. Vizimpro® (dacomitinib) tablets prescribing information. New York, NY; 2020 Dec.
2. Wu YL, Cheng Y, Zhou X et al. Dacomitinib versus gefitinib as first-line treatment for patients with EGFR-mutation-positive non-small-cell lung cancer (ARCHER 1050): a randomised, open-label, phase 3 trial. Lancet Oncol . 2017; 18:1454-1466. [PubMed 28958502]
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9. Nelson V, Ziehr J, Agulnik M et al. Afatinib: emerging next-generation tyrosine kinase inhibitor for NSCLC. Onco Targets Ther . 2013; 6:135-43.
10. Köhler J, Schuler M. Afatinib, erlotinib and gefitinib in the first-line therapy of EGFR mutation-positive lung adenocarcinoma: a review. Onkologie . 2013; 36:510-8.
11. Li D, Ambrogio L, Shimamura T et al. BIBW2992, an irreversible EGFR/HER2 inhibitor highly effective in preclinical lung cancer models. Oncogene . 2008; 27:4702-11.
12. Jotte RM, Spigel DR. Advances in molecular-based personalized non-small-cell lung cancer therapy: targeting epidermal growth factor receptor and mechanisms of resistance. Cancer Med . 2015; 4:1621-32. [PubMed 26310719]
13. Takahashi T, Boku N, Murakami H et al. Phase I and pharmacokinetic study of dacomitinib (PF-00299804), an oral irreversible, small molecule inhibitor of human epidermal growth factor receptor-1, -2, and -4 tyrosine kinases, in Japanese patients with advanced solid tumors. Invest New Drugs . 2012; 30:2352-63. [PubMed 22249430]
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15. AstraZeneca Pharmaceuticals LP. Iressa® (gefitinib) tablets prescribing information. Wilmington, DE; 2018 Aug.
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22. Lacouture ME, Keefe DM, Sonis S et al. A phase II study (ARCHER 1042) to evaluate prophylactic treatment of dacomitinib-induced dermatologic and gastrointestinal adverse events in advanced non-small-cell lung cancer. Ann Oncol . 2016; 27:1712-8. [PubMed 27287210]
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