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
Mené sur 285 patients atteints d'un adénocarcinome pulmonaire EGFR positif de stade avancé, cet essai de phase III compare l'efficacité, du point de vue de la survie sans progression, et la toxicité de l'icotinib en traitement de première ligne et d'un traitement d'entretien à base de cisplatine et de pémétrexed
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.