Updated Overall Survival and Exploratory Analysis From Randomized, Phase II EVAN Study of Erlotinib Versus Vinorelbine Plus Cisplatin Adjuvant Therapy in Stage IIIA Epidermal Growth Factor Receptor+ Non-Small-Cell Lung Cancer

Abstract

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.The randomized, open-label, phase II EVAN study investigated the efficacy (disease-free survival [DFS] and 5-year overall survival [OS]) and safety of erlotinib versus vinorelbine/cisplatin as adjuvant chemotherapy after complete resection (R0) for stage III epidermal growth factor receptor (EGFR) mutation+ non-small-cell lung cancer. We describe the updated results at the 43-month follow-up. In EVAN, patients were randomly assigned (1:1) to erlotinib (n = 51) or vinorelbine/cisplatin (n = 51). The median follow-up was 54.8 and 63.9 months in the erlotinib and chemotherapy arms, respectively. With erlotinib, the respective 5-year DFS by Kaplan-Meier analysis was 48.2% (95% CI, 29.4 to 64.7) and 46.2% (95% CI, 27.6 to 62.9) in the intention-to-treat and per-protocol populations. The median OS was 84.2 months with erlotinib versus 61.1 months with chemotherapy (hazard ratio, 0.318; 95% CI, 0.151 to 0.670). The 5-year survival rates were 84.8% and 51.1% with erlotinib and chemotherapy, respectively. In whole-exome sequencing analysis, frequent genes with variants co-occurring at baseline were TP53, MUC16, FAM104B, KMT5A, and DNAH9. With erlotinib, a single-nucleotide polymorphism mutation in UBXN11 was associated with significantly worse DFS (P = .01). To our knowledge, this study is the first to demonstrate clinically meaningful OS improvement with adjuvant erlotinib compared with chemotherapy in R0 stage III EGFR+ non-small-cell lung cancer.

Trial registration: ClinicalTrials.gov NCT01683175.