LKB1 mutations 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
Adele Busico,
Valter Torri,
Giulia Galli,
Giuseppe Lo Russo,
Claudia Proto,
Monica Ganzinelli,
Claudio Vernieri,
Diego Signorelli,
Eliana Rulli,
Gabriella Farina,
Anna Cecilia Bettini,
Claudia Bareggi,
Lorenzo Rosso,
Massimo Moro,
Stefano Indraccolo,
Gabriella Sozzi,
Mirko Marabese,
Broggini Massimo,
Marina C. Garassino
Affiliations
Adele Busico
Pathology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Lombardia, Italy
Valter Torri
Laboratory of Methodology for Clinical Research, Oncology Department, Istituto di Ricerche Farmacologiche Mario Negri Sede di Milano, Milano, Lombardia, Italy
Giulia Galli
Unit of Thoracic Oncology, Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Lombardia, Italy
Giuseppe Lo Russo
Unit of Thoracic Oncology, Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Lombardia, Italy
Claudia Proto
Unit of Thoracic Oncology, Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Lombardia, Italy
Monica Ganzinelli
Unit of Thoracic Oncology, Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Lombardia, Italy
Claudio Vernieri
Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy
Diego Signorelli
Unit of Thoracic Oncology, Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Lombardia, Italy
Eliana Rulli
Laboratory of Methodology for Clinical Research, Oncology Department, Istituto di Ricerche Farmacologiche Mario Negri Sede di Milano, Milano, Lombardia, Italy
Gabriella Farina
Department of Oncology, ASST Fatebenefratelli Sacco, Milano, Lombardia, Italy
Anna Cecilia Bettini
Oncology Department, ASST Papa Giovanni XXIII, Bergamo, Lombardia, Italy
Claudia Bareggi
Oncology Unit, La Fondazione IRCCS Ca' Granda Ospedale Maggiore di Milano Policlinico, Milano, Lombardia, Italy
Lorenzo Rosso
Thoracic Surgery and Lung Transplant Unit, La Fondazione IRCCS Ca' Granda Ospedale Maggiore di Milano Policlinico, Milano, Lombardia, Italy
Massimo Moro
Tumor Genomics Unit, Department of Research, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Lombardia, Italy
Stefano Indraccolo
Immunology and Molecular Oncology Unit, Istituto Oncologico Veneto Istituto di Ricovero e Cura a Carattere Scientifico, Padova, Veneto, Italy
Gabriella Sozzi
Tumor Genomics Unit, Department of Research, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Lombardia, Italy
Mirko Marabese
Laboratory of Molecular Pharmacology, Oncology Department, Istituto di Ricerche Farmacologiche Mario Negri Sede di Milano, Milano, Lombardia, Italy
Broggini Massimo
Laboratory of Molecular Pharmacology, Istituto di Ricerche Farmacologiche Mario Negri Sede di Milano, Milano, Lombardia, Italy
Marina C. Garassino
Unit of Thoracic Oncology, Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Lombardia, Italy
Purpose In patients with advanced lung adenocarcinoma, the impact of LKB1 mutations on cytotoxic chemotherapy efficacy remains poorly explored. Here, we aimed at investigating the potential impact of LKB1 mutational 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 with EGFR-wild type (wt) advanced NSCLC progressing on/after previous platinum-based chemotherapy to receive docetaxel or erlotinib. Here, we evaluated the impact of LKB1 mutational 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 evaluable LKB1 status were included. Of them, 17 (14.17%) patients had LKB1-mutated tumours, while 103 (85.83%) had LKB1-wt disease. During second-line treatment, PFS and OS were not statistically significantly different in patients with LKB1-mutated when compared with LKB1-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 between LKB1 mutations 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, LKB1 mutations 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.
