Dacomitinib Approved for Non-Small Cell Lung Cancer

Drug Topics JournalDrug Topics December 2018
Volume 162
Issue 12

Approved by the FDA in September, this new drug serves as a first-line therapy for patients with particular metastatic non-small lung cancer.

Cancer Ribbons

In September, the FDA approved dacomitinib (Vizimpro, Pfizer), a second-generation selective nonreversible inhibitor of epidermal growth factor receptor (EGFR), as a first-line therapy for patients with metastatic non-small cell lung cancer (NSCLC) with EGFR exon 19 deletion or exon 21 L858R substitution mutation detected by an FDA-approved test.1
EGFR is a transmembrane protein growth-signaling receptor. It’s over expression has been implicated in numerous human cancers with most prominence in lung, head and neck, and glioblastomas.2


Approval of dacomitinib was based on a randomized controlled multicenter open-label clinical trial enrolling 452 patients with unresectable stage IIIB/IV EGFR-positive NSCLC (ARCHER 1050).3 The ARCHER trial consisted of two arms comparing safety and efficacy of dacomitinib versus gefitinib, a previous first-line therapy option for EGFR-positive NSCLC.

Patients in the dacomitinib arm received 45 mg by mouth daily, while gefitinib was dosed at 250 mg by mouth daily. The primary outcome measure was progression-free survival (PFS) as determined by blinded Independent radiological central review panel

To be enrolled in the trial, patients had to have an Eastern Cooperative Oncology Group performance status score of 0 or 1. They also had to have no prior therapy for metastatic disease or be at least 12 months without recurrent disease.

The trial showed improvement in median PFS at 14.7 months (95% confidence interval [CI], 11.1-16.6) in the dacomitinib arm and 9.2 months (95% CI, 9.1-11.0) in the gefitinib arm (hazard ratio [HR], 0.59, 95% CI, 0·47-0·74; p<0·0001). Median duration of follow-up for progression-free survival was 22.1 months (95% CI, 20.3-23.9).2

Overall survival was also improved, with a median overall survival time of 34.1 months with dacomitinib compared with 26.8 months with gefitinib (HR, 0.76; 95% CI, 0.582-0.993, p=0.44).4



Of the 227 patients who received dacomitinib, 27% experienced serious adverse reactions. The most common adverse events reported included diarrhea (87%), paronychia (61%), acneiform rash (49%), stomatitis (44%), decreased appetite (31%), dry skin (27%), decreased weight (25%), alopecia (24%), cough (21%), and pruritus (20%).3 Interstitial lung disease (ILD,  0.4%) and grade 3 diarrhea (8%) were the two side effects that most frequently resulted in discontinuation of the study drug.

For patients developing respiratory symptoms (cough, shortness of breath) indicative of possible ILD, dacomitinib should be held.5 If these symptoms worsen (exertional dyspnea, fever) or ILD is confirmed, treatment should be permanently discontinued.

Patients who develop grade 3 to 4 diarrhea should have their medication held until symptoms resolve and then should be restarted at the same or lower dose. Diarrhea should be treated at the onset with antidiarrheals (loperamide or diphenoxylate hydrochloride/ atropine sulfate).5

Dacomitinib exhibits a drug-drug interaction with proton pump inhibitors, which should be discontinued; histamine-2 receptor antagonists and antacids are permitted. Medications that are cytochrome P450 (CYP)2D6 substrates also exhibit interactions with dacomitinib and should be avoided as concomitant usage can cause elevated medication levels.

Females with childbearing potential should be advised to use effective contraception while taking, and for at least 17 days after discontinuing, dacomitinib.



Recommended dosing for dacomitinib is 45 mg daily by mouth, with or without food. If a dose is missed, or vomiting occurs shortly after taking, another dose should not be taken. Patients should resume with the next scheduled dose of the medication.

This medication is available in 15-mg, 30-mg, and 45-mg formulations.5

Matthew J. Hadfield, DO is an intern in internal medicine at UConn Health.

Lisa M. Holle, PharmD, BCOP, FHOPA, is associate clinical professor with the University of Connecticut School of Pharmacy in Storrs.

Page 2: References


1. Center for Drug Evaluation and Research. (2018, September 28). Approved Drugs - FDA approves dacomitinib for metastatic non-small cell lung cancer. Retrieved Oct. 30, 2018, from https://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm621967.htm.

2. Harari PM. Epidermal growth factor receptor inhibition strategies in oncology. Endocrine-related cancer 11.4 (2004): 689-708.

3. Wu YL 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 18.11 (2017): 1454-1466.

4. Mok TS, Cheng Y, Zhoe X, et al. Improvement in overall survival in a randomized study that compared dacomitinib with gefitinib in patients with advanced non-small-cell lung cancer and EGFR activating mutations. J Clin Oncol. 36 (2018): 2244-2250.

5. Package Insert. Vizimpro.  November 2018.Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/211288s000lbl.pdf. Accessed on Nov. 13, 2018.

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