E Rulli1, M Marabese1, V Torri1, G Farina2, S Veronese3, A Bettini4, F Longo5, L Moscetti6, M Ganzinelli7, C Lauricella3, E Copreni1, R Labianca4, O Martelli8, S Marsoni9, M Broggini10, M C Garassino7. 1. Department of Oncology, IRCCS-Istituto di Ricerche Farmacologiche 'Mario Negri', Milan. 2. Department of Medical Oncology, Fatebenefratelli e Oftalmico Hospital, Milan. 3. Department of Pathology, Niguarda Cancer Center, Ospedale Niguarda Cà Granda, Milan. 4. Department of Medical Oncology, Papa Giovanni XXIII Hospital, Bergamo. 5. Department of Medical Oncology, Università La Sapienza, Policlinico Umberto I, Rome. 6. Department of Medical Oncology, Ospedale Belcolle, Viterbo. 7. Thoracic Oncology Unit, Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan. 8. Department of Medical Oncology, Ospedale San Giovanni e Addolorata, Rome. 9. Clinical Trials Coordination Unit, Istituto di Candiolo-FPO, IRCCS, Candiolo, Italy. 10. Department of Oncology, IRCCS-Istituto di Ricerche Farmacologiche 'Mario Negri', Milan massimo.broggini@marionegri.it.
Abstract
BACKGROUND: The prognostic and predictive role of KRAS mutations in advanced nonsmall-cell lung cancer (NSCLC) is still unclear. TAILOR prospectively assessed the prognostic and predictive value of KRAS mutations in NSCLC patients treated with erlotinib or docetaxel in second line. PATIENTS AND METHODS: NSCLC patients from 52 Italian hospitals were genotyped for KRAS and EGFR mutational status in two independent laboratories. Wild-type EGFR patients (N = 218) receivedfirst-line platinum-based chemotherapy and were randomly allocated at progression to erlotinib or docetaxel. Overall survival (OS) according to KRAS mutational status was the primary end point. RESULTS:KRAS mutations were present in 23% of TAILOR randomized cases. The presence of a KRAS mutation did not adversely affect progression-free (PFS) or overall (OS) survival [hazard ratio (HR) PFS = 1.01, 95% confidence interval (CI) 0.71-1.41, P = 0.977; OS = 1.24, 95% CI 0.87-1.77, P = 0.233], nor influenced treatment outcome (test for interaction: OS P = 0.965; PFS P = 0.417). Patients randomized to docetaxel treatment experienced longer survival independently from the KRAS mutational status of their tumors (HR: mutated KRAS 0.81, 95% CI 0.45-1.47; wild-type KRAS 0.79, 95% CI 0.57-1.10). CONCLUSION: In TAILOR, KRAS was neither prognostic nor predictive of benefit for either docetaxel or erlotinib. Docetaxel remains superior independently from KRAS status for second-line treatment in EGFR wild-type advanced NSCLC patients. CLINICAL TRIAL REGISTRATION: NCT00637910.
RCT Entities:
BACKGROUND: The prognostic and predictive role of KRAS mutations in advanced nonsmall-cell lung cancer (NSCLC) is still unclear. TAILOR prospectively assessed the prognostic and predictive value of KRAS mutations in NSCLCpatients treated with erlotinib or docetaxel in second line. PATIENTS AND METHODS: NSCLCpatients from 52 Italian hospitals were genotyped for KRAS and EGFR mutational status in two independent laboratories. Wild-type EGFRpatients (N = 218) received first-line platinum-based chemotherapy and were randomly allocated at progression to erlotinib or docetaxel. Overall survival (OS) according to KRAS mutational status was the primary end point. RESULTS:KRAS mutations were present in 23% of TAILOR randomized cases. The presence of a KRAS mutation did not adversely affect progression-free (PFS) or overall (OS) survival [hazard ratio (HR) PFS = 1.01, 95% confidence interval (CI) 0.71-1.41, P = 0.977; OS = 1.24, 95% CI 0.87-1.77, P = 0.233], nor influenced treatment outcome (test for interaction: OS P = 0.965; PFS P = 0.417). Patients randomized to docetaxel treatment experienced longer survival independently from the KRAS mutational status of their tumors (HR: mutated KRAS 0.81, 95% CI 0.45-1.47; wild-type KRAS 0.79, 95% CI 0.57-1.10). CONCLUSION: In TAILOR, KRAS was neither prognostic nor predictive of benefit for either docetaxel or erlotinib. Docetaxel remains superior independently from KRAS status for second-line treatment in EGFR wild-type advanced NSCLCpatients. CLINICAL TRIAL REGISTRATION: NCT00637910.
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