LKB1mutations are not associated with the efficacy of first-line and second-line chemotherapy in patients with advanced non-small-cell lung cancer (NSCLC): a post hoc analysis of the TAILOR trial

Abstract

Purpose In patients with advanced lung adenocarcinoma, the impact ofLKB1mutations on cytotoxic chemotherapy efficacy remains poorly explored. Here, we aimed at investigating the potential impact ofLKB1mutational status on chemotherapy efficacy in advanced non-small-cell lung cancer (NSCLC) patients enrolled in the TArceva Italian Lung Optimisation tRial (TAILOR) trial. Methods The multicenter TAILOR trial randomised patients withEGFR-wild type (wt) advanced NSCLC progressing on/after previous platinum-based chemotherapy to receive docetaxel or erlotinib. Here, we evaluated the impact ofLKB1mutational status on progression-free survival (PFS) and overall survival (OS) in patients treated with second-line docetaxel/erlotinib or during prior platinum-based chemotherapy. Results Out of 222 patients randomised in the TAILOR trial, left-over tumour tissues were available for 188 patients, and 120 patients with evaluableLKB1status were included. Of them, 17 (14.17%) patients hadLKB1-mutated tumours, while 103 (85.83%) hadLKB1-wt disease. During second-line treatment, PFS and OS were not statistically significantly different in patients withLKB1-mutated when compared withLKB1-wt NSCLC (adjusted HR (aHR)=1.29, 95% CI 0.75 to 2.21; p=0.364 and aHR=1.41, 95% CI 0.82 to 2.44; p=0.218, respectively). Similarly, we found no significant association betweenLKB1mutations and patient PFS or OS during prior first-line platinum-based chemotherapy (aHR=1.04, 95% CI 0.55 to 1.97; p=0.910 and aHR=0.83, 95% CI 0.42 to 1.65; p=0.602, respectively). Conclusion Among advanced NSCLC patients receiving two lines of systemic therapy,LKB1mutations were not associated with PFS or OS during second-line docetaxel or prior first-line platinum-based chemotherapy. While larger prospective trials are needed to confirm our findings, cytotoxic chemotherapy remains the backbone of investigational combination strategies in this patient population.