On September 27, 2018, the FDA approved the targeted therapy dacomitinib (Vizimpro; Pfizer), an oral kinase inhibitor, for the first-line treatment of patients with metastatic non–small-cell lung cancer (NSCLC) associated with EGFR exon 19 deletion or exon 21 L858R substitution mutations, as identified by an FDA-approved test. The FDA approved dacomitinib using its priority review process and granted it an orphan drug designation.
This approval was based on the clinical trial ARCHER 1050, a randomized, multicenter, open-label, active-controlled study of 452 patients with unresectable, metastatic NSCLC. Patients had to be disease free for at least 12 months and could not have received treatment for metastatic disease. All patients had a 0 or 1 Eastern Cooperative Oncology Group performance status, as well as EGFR exon 19 deletion or exon 21 L858R substitution mutations. The patients were randomized in a 1:1 ratio to dacomitinib 45 mg once daily or to gefitinib (Iressa) 250 mg once daily until disease progression or unacceptable toxicity.
The median progression-free survival (PFS) was 14.7 months in the dacomitinib arm versus 9.2 months in the gefitinib arm, a significant improvement in PFS (hazard ratio, 0.59; 95% confidence interval, 0.47-0.74; P <.0001). However, no improvement was seen in overall survival.
Dacomitinib is associated with the risk for interstitial lung disease, diarrhea, and dermatologic reactions. Overall, 27% of patients in the ARCHER study had serious adverse events; the most common reasons for treatment discontinuation were diarrhea and interstitial lung disease. The most common (>20%) adverse events with dacomitinib were diarrhea, rash, paronychia, stomatitis, decreased appetite, dry skin, decreased weight, alopecia, cough, and pruritus.