Gefitinib failed to meet its noninferiority endpoint, compared with erlotinib, but was significantly less likely to cause grade 3 rash in a multicenter, randomized phase III trial of patients with advanced, pretreated lung adenocarcinoma.

“Subset analysis including mutation status did not reveal any populations with noteworthy differences in clinical efficacy between gefitinib and erlotinib,” said Dr. Yoshiko Urata at Hyogo Cawncer Center in Akashi, Japan, and associates. Nonetheless, gefitinib could be a therapeutic option, given its milder adverse effects in this patient population, the investigators reported online in the Journal of Clinical Oncology.

Both gefitinib and erlotinib are first-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors. Gefitinib had a higher response rate in Japanese patients than in non-Japanese patients in a prior phase II trial. Erlotinib yielded better survival results than gefitinib in subsequent trials, but the two agents had never been compared directly in a phase III trial, according to the investigators (J. Clin. Oncol. 2016 Mar. 28. doi: 10.1200/JCO.2015.63.4154).

Their study included 561 patients, of whom 401 had the EGFR mutation. Baseline factors except performance status were balanced between the randomization arms. Erlotinib was dosed at 150 mg/day, and gefitinib at 250 mg/day. In the event of toxicities, erlotinib could be lowered to 100 mg and 50 mg, and gefitinib to 250 mg on alternate days and 250 mg once every 3 days.

The median progression-free survival (PFS) was 6.5 months for gefitinib and 7.5 months for erlotinib (hazard ratio, 1.1; 95% confidence interval, 0.9-1.4; P = .26). The median PFS also did not statistically differ according to treatment in patients with the EGFR mutation (8.3 and 10.0 months, respectively; HR, 1.1; 95% CI, 0.9-1.4). The median overall survival was 22.8 months for gefitinib and 24.5 months for erlotinib (HR, 1.04; 95% CI, 0.833-1.29). The response rates were 45.9% and 44.1%, respectively.

The most common grade 3-4 toxicities included rash and increases in liver enzymes, said the researchers. Notably, grade 3 rash affected 18% of erlotinib patients and only 2% of gefitinib patients; no patients had grade 4 rash. Gefitinib was linked to three to four times the rate of increased liver enzymes, but an overall analysis of adverse effects nonetheless favored gefitinib (P less than .001).


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