(CHICAGO, IL) – Intercalating erlotinib with platinum-based chemotherapy prolongs progression-free survival (PFS) in first-line advanced  non-small cell lung cancer (NSCLC), according to the results of a the Phase 3 FASTACT-II trial presented at the 2012 American Society of Clinical Oncology Annual Meeting.

In FASTACT-I, a Phase 2 trial, intercalating erlotinib with first-line platinum-based chemotherapy was found to significantly prolong PFS vs. chemotherapy alone; FASTACT-II is a confirmatory, randomized, Phase 3, placebo-controlled, double-blind study in a large patient population. Lead author Tony Mok, MD, of Chinese University of Hong Kong, explained that in FASTACT-II, untreated stage 3B/4 NSCLC patients received gemcitabine plus platinum-based chemotherapy (carboplatin or cisplatin) with either intercalated erlotinib or placebo.

For the 451 patients randomized to receive erlotinib or placebo, the primary endpoint of PFS was significantly prolonged with erlotinib compared with placebo, with a median PFS of 7.6 vs. 6.0 months, respectively; (HR=0.57 [95% CI 0.46–0.70]; P<0.0001). A secondary endpoint of overall response rate was also significantly improved with erlotinib compared with placebo: 42.9% vs. 17.8%; P<0.0001. Although data for overall survival (OS), another secondary endpoint, are not yet mature and may be confounded by a high crossover rate (73%) to second-line erlotinib by placebo-arm patients, Dr. Mok noted, a non-significant trend toward longer OS was seen with erlotinib vs. placebo with a median of 18.3 vs. 14.9 months (HR=0.78 [95% CI 0.60–1.02]; P=0.069). Except for skin rash with erlotinib, there was no clinically significant difference in toxicity between arms. A total of 283 patients (62.7%) provided samples for biomarker analyses, including EGFR mutation status, analyses of which are ongoing, Dr. Mok and colleagues reported.

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Dr. Mok and colleagues concluded that intercalation of erlotinib with chemotherapy significantly prolonged PFS in first-line advanced NSCLC. He added that biomarker analysis will determine the significance of this regimen in patients with or without activating EGFR mutations.