First-line icotinib versus cisplatin/pemetrexed plus pemetrexed maintenance therapy for patients with advanced EGFR mutation-positive lung adenocarcinoma (CONVINCE): a phase 3, open-label, randomized study

Abstract

Background: Icotinib has been previously shown to be non-inferior to gefitinib in non-selected advanced non-small cell lung cancer (NSCLC) patients when given as second- or further-line treatment. In this open-label, randomized, phase 3 CONVINCE trial, we assessed the efficacy and safety of first-line icotinib versus cisplatin/pemetrexed plus pemetrexed maintenance in lung adenocarcinoma patients with epidermal growth factor receptor (EGFR) mutation.Patients and methods: Eligible participants were adults with stage IIIB/IV lung adenocarcinoma and exon 19/21 EGFR mutations. Participants were randomly allocated (1:1) to receive oral icotinib or 3-week cycle of cisplatin plus pemetrexed for up to 4 cycles; non-progressive patients after 4 cycles were maintained with pemetrexed until disease progression or intolerable toxicity. The primary endpoint was progression-free survival (PFS) assessed by independent response evaluation committee (IREC). Other endpoints included overall survival (OS) and safety.Results: Between Jan 2013 and Aug 2014, 296 patients were randomized, and 285 patients were treated (148 to icotinib, 137 to chemotherapy). IREC-assessed PFS was significantly longer in the icotinib group (11.2 vs 7.9 months; hazard ratio, 0.61, 95% confidence interval 0.43-0.87; P = 0.006). No significant difference for OS was observed between treatments in the overall population or in EGFR-mutated subgroups (exon 19 Del/21 L858R). The most common grade 3 or 4 adverse events (AEs) in the icotinib group were rash (14.8%) and diarrhea (7.4%), compared with nausea (45.9%), vomiting (29.2%), and neutropenia (10.9%) in the chemotherapy group. AEs (79.1% vs 94.2%; P < 0.001) and treatment-related AEs (54.1% vs 90.5%; P < 0.001) were significantly fewer in the icotinib group than in the chemotherapy group.Conclusions: First-line icotinib significantly improves PFS of advanced lung adenocarcinoma patients with EGFR mutation with a tolerable and manageable safety profile. Icotinib should be considered as a first-line treatment for this patient population.ClinicalTrials.gov Registration Number NCT01719536.

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