Dacomitinib (Vizimpro) Approved for First-Line Use in EGFRm NSCLC

Zosia Chustecka


September 28, 2018

A new targeted agent has been approved in the United States for first-line use in the treatment of metastatic non–small cell lung cancer (NSCLC).

Dacomitinib (Vizimpro, Pfizer) was approved by the US Food and Drug Administration (FDA) for the first-line treatment of patients with metastatic NSCLC with epidermal growth factor receptor (EGFR) exon 19 deletion or exon 21 L858R substitution mutations, as detected by an FDA-approved test.

This approval was based on data from the ARCHER 1050 trial, in which the new drug, a second-generation tyrosine kinase inhibitor, was compared to the first targeted agent used for EGFR-mutated NSCLC, gefitinib (Iressa, AstraZeneca).

The trial was conducted in 452 patients with unresectable, metastatic NSCLC who had received no prior therapy for metastatic disease, and also in patients with recurrent disease who had been disease free for a minimum of 12 months after completion of systemic therapy.

The results showed a statistically significant improvement in progression-free survival (PFS) with the newer agent: median PFS was 14.7 months with dacomitinib compared with 9.2 months with gefitinib (hazard ratio, 0.59; P < .0001).

The FDA notes that no improvement was seen in overall response rate or overall survival.

"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," commented principal investigator Tony Mok, MD, professor and chair of the Department of Clinical Oncology at the Chinese University of Hong Kong, China, in a company press release.

However, toxicity was higher with dacomitinib; 66% of patients required a dose reduction, compared to 8% for those who received gefitinib, Mok noted when he presented the results at the 2017 annual meeting of the American Society of Clinical Oncology (ASCO).

Thus, patients should be aware of the potential side effects when making treatment decisions, he commented.

At the time, ASCO expert John V. Heymach, MD, PhD, from the University of Texas MD Anderson Cancer Center, Houston, also highlighted the toxicity that occurred.

"In this study, we see more than a 5-month difference in progression-free survival," he said. "From the perspective of doctors who treat lung cancer, this is a substantial advance, and I think it really puts dacomitinib at the front of the pack in terms of efficacy."

However, the efficacy does come at the cost of some toxicity. "About 10% of patients had grade 3 toxicity involving skin and diarrhea, and a substantial number had dose reductions, but I'd like to emphasize that these aren't life-threatening toxicities," said Dr Heymach. "These are toxicities that doctors who treat this for a living become accustomed to managing. This drug clearly requires close monitoring and careful surveillance by experienced care providers to manage toxicities."

Overall, dacomitinib appears to be a clear, potential option for patients, he added. "And as a physician, I think discussing the different options in the trade-off of toxicity vs efficacy would be entirely appropriate," he commented at the time.

The manufacturer's press release provides details of the toxicity that was seen. Among 227 patients with EGFR-mutated metastatic NSCLC who received dacomitinib in the ARCHER 1050 trial, the most common (>20%) adverse reactions were diarrhea (87%), rash (69%), paronychia (64%), stomatitis (45%), decreased appetite (31%), dry skin (30%), decreased weight (26%), alopecia (23%), cough (21%), and pruritus (21%). Serious adverse reactions occurred in 27% patients; the most common (≥1%) serious adverse reactions reported were diarrhea (2.2%) and interstitial lung disease (1.3%).

Full prescribing information for dacomitinib can be found here.

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