The FDA has approved dacomitinib tablets (Vizimpro®, Pfizer) for first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 19 deletion or exon 21 L858R substitution mutations.
Comprising approximately 85% of lung cancer cases, NSCLC is challenging to treat, especially when it has metastasized. Around 75% of NSCLC patients remain undiagnosed until they have reached a state of advanced or metastatic disease, which has a 5-year survival rate of only 5%.
EGFR is involved in processes promoting cell proliferation and survival, and genetic mutations causing EGFR overexpression can result in the formation of cancer cells. These mutations are estimated to occur in 10% to 35% of NSCLC tumors. Exon 19 deletions and exon 21 L858R substitutions are the most common, accounting for over 80% of all known activating EGFR mutations.
Approval of dacomitinib was based on the ARCHER 1050 trial (NCT01774721), an international, multicenter, randomized, open-label trial enrolling 452 adult patients with newly diagnosed advanced NSCLC and one EGFR mutation (exon 19 deletion or exon 21 L858R substitution). Dacomitinib produced a median progression-free survival of 14.7 months, compared with 9.2 months for gefitinib (Iressa®, AstraZeneca).
In 394 patients receiving dacomitinib, 27% experienced serious adverse reactions, with diarrhea and interstitial lung disease (ILD) as the reactions most frequently resulting in treatment discontinuation. Adverse reactions occurring in over 20% of patients included diarrhea, rash, paronychia, stomatitis, decreased appetite, dry skin, decreased weight, alopecia, cough, and pruritus. The prescribing information contains warnings and precautions for ILD, diarrhea, and dermatologic reactions. The recommended dose of dacomitinib is 45 mg orally once daily, with or without food. The EGFR mutations must be detected by an FDA-approved test.
"EGFR-mutated advanced non-small cell lung cancer is a common illness, especially in the Asian population, and new treatment options will ultimately benefit patients," stated Tony Mok, MD, senior investigator for the ARCHER 1050 study and chair of the Department of Clinical Oncology at The Chinese University of Hong Kong. "The findings from ARCHER 1050 suggest that [dacomitinib] should be considered as a new first-line treatment option for patients with EGFR-mutated non-small cell lung cancer exon 19 deletion or exon 21 L858R substitution mutations."
For More Information
Wu YL, Cheng Y, Zhou X, et al (2017). 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):1454-1466. DOI:10.1016/S1470-2045(17)30608-3