European approval is expected soon for a new targeted agent for use in the first-line treatment of patients with locally advanced or metastatic non–small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) activating mutations.
The new agent, dacomitinib (Vizimpro, Pfizer) was given a positive opinion at the latest meeting of the European Committee for Medicinal Products for Human Use (CHMP); a European approval usually follows within 67 days.
Dacomitinib is already approved for this indication in the United States.
The CHMP said in a press release that the benefits with dacomitinib are “its ability to increase progression free survival (PFS) compared with gefitinib [Iressa, AstraZeneca].”
This appears to be referring to the results from the ARCHER 1050 trial, which was the basis for the US approval. That trial was conducted in 452 patients with unresectable, metastatic NSCLC who had received no prior therapy for metastatic disease and 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 PFS with the new agent: median PFS was 14.7 months with dacomitinib, compared with 9.2 months with gefitinib (hazard ratio, 0.59; P < .0001).
However, there was no improvement 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 at the time of the US approval.
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 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 clearly appears to be a 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 CHMP notes that the most common side effects are diarrhea, rash, stomatitis, nail disorder, dry skin, decreased appetite, conjunctivitis, weight loss, alopecia, pruritus, increased transaminase levels, and nausea.
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