2017 ASCO Annual Meeting!
Session: Lung Cancer—Non-Small Cell Metastatic
Type: Oral Abstract Session
Time: Tuesday June 6, 9:45 AM to 12:45 PM
Location: Hall D1
Alectinib versus crizotinib in treatment-naive advanced ALK-positive non-small cell lung cancer (NSCLC): Primary results of the global phase III ALEX study.
Metastatic Non-Small Cell Lung Cancer
Lung Cancer—Non-Small Cell Metastatic
2017 ASCO Annual Meeting
J Clin Oncol 35, 2017 (suppl; abstr LBA9008)
Author(s): Alice Tsang Shaw, Solange Peters, Tony Mok, Shirish M. Gadgeel, Jin Seok Ahn, Sai-Hong Ignatius Ou, Maurice Perol, Rafal Dziadziuszko, Dong-Wan Kim, Rafael Rosell, Ali Hassan Zeaiter, Ting Liu, Sophie Golding, Bogdana Balas, Johannes Noé, Peter N. Morcos, D. Ross Camidge; Massachusetts General Hospital, Boston, MA; Lausanne Universtiy Hospital, Lausanne, Switzerland; Chinese University of Hong Kong, Hong Kong, China; Karmanos Cancer Institute, Detroit, MI; Sungkyunkwan University School of Medicine, Seoul, Republic of Korea; Chao Family Comprehensive Cancer Center, University of California, Irvine School of Medicine, Orange, CA; Department of Thoracic Oncology, Centre Léon Bérard, Lyon, France; Medical University of Gdańsk, Department of Oncology and Radiotherapy, Gdańsk, Poland; Seoul National University Hospital, Seoul, Republic of Korea; Catalan Institute of Oncology, Barcelona, Spain; F. Hoffmann-La Roche Ltd., Basel, Switzerland; Roche Innovation Center, New York, NY; University of Colorado-Denver, Aurora, CO
Background: Alectinib, a TKI targeting ALK, has shown robust efficacy in crizotinib-naïve/resistant ALK+ NSCLC. J-ALEX showed superiority of alectinib 300mg BID vs crizotinib in Japanese pts with crizotinib-naïve ALK+ NSCLC (progression-free survival [PFS] HR 0.34, p<0.0001). We report primary results from the ALEX study of first-line alectinib 600mg BID vs crizotinib in advanced ALK+ NSCLC (NCT02075840). Methods: This open-label randomized multicenter phase III study enrolled pts with stage IIIB/IV ALK+ NSCLC, determined by central IHC testing. Eligible pts had ECOG PS 0–2 and no prior systemic therapy for advanced NSCLC. Pts with asymptomatic CNS metastases were allowed. Pts (n=303) were randomized 1:1 to receive alectinib 600mg or crizotinib 250mg BID. Primary endpoint: Investigator (Inv)-assessed PFS (RECIST v1.1), with systematic CNS imaging in all pts. Secondary endpoints included independent review committee (IRC)-assessed PFS, IRC-assessed time to CNS progression (TTP), objective response rate (ORR), overall survival (OS) and safety. Results: At the primary data cut-off (9 Feb 2017), alectinib demonstrated statistically significant superiority vs crizotinib, reducing risk of progression/death by 53% (HR 0.47, 95% CI 0.34–0.65, p<0.0001); alectinib median PFS was not reached (95% CI 17.7–NE) vs crizotinib 11.1 months (95% CI 9.1–13.1). Key secondary endpoints showed superiority for alectinib vs crizotinib, respectively: IRC PFS, HR 0.50 (95% CI 0.36–0.70; p<0.0001); median PFS 25.7 months (95% CI 19.9–NE) vs 10.4 months (95% CI 7.7–14.6); CNS TTP, cause-specific HR of CNS progression 0.16 (95% CI 0.10–0.28; p<0.0001); ORR (Inv) 83% (95% CI 76–89) vs 76% (95% CI 68–82), p=0.09; OS, based on 25% events, HR 0.76 (95% CI 0.48–1.20; p=0.24). Grade 3/4 AEs were less frequent with alectinib, 41%, vs 50% with crizotinib; fatal AEs occurred in 3% vs 5%, respectively. Rates of AEs leading to discontinuation, dose reduction and interruption were lower with alectinib. Conclusions: Alectinib showed superior efficacy and favorable tolerability compared with crizotinib. ALEX results support alectinib as a new standard of care for treatment-naïve ALK+ NSCLC. Funding: F. Hoffmann-La Roche Clinical trial information: NCT02075840
1. Efficacy, safety, and biomarker results of trastuzumab emtansine (T-DM1) in patients (pts) with previously treated HER2-overexpressing locally advanced or metastatic non-small cell lung cancer (mNSCLC).