PMID- 28689043 OWN - NLM STAT- MEDLINE DCOM- 20180611 LR - 20220311 IS - 1556-1380 (Electronic) IS - 1556-0864 (Print) IS - 1556-0864 (Linking) VI - 12 IP - 10 DP - 2017 Oct TI - Pooled Systemic Efficacy and Safety Data from the Pivotal Phase II Studies (NP28673 and NP28761) of Alectinib in ALK-positive Non-Small Cell Lung Cancer. PG - 1552-1560 LID - S1556-0864(17)30570-1 [pii] LID - 10.1016/j.jtho.2017.06.070 [doi] AB - INTRODUCTION: Alectinib demonstrated clinical efficacy and an acceptable safety profile in two phase II studies (NP28761 and NP28673). Here we report the pooled efficacy and safety data after 15 and 18 months more follow-up than in the respective primary analyses. METHODS: Enrolled patients had ALK receptor tyrosine kinase gene (ALK)-positive NSCLC and had progressed while taking, or could not tolerate, crizotinib. Patients received oral alectinib, 600 mg twice daily. The primary end point in both studies was objective response rate assessed by an independent review committee (IRC) using the Response Evaluation Criteria in Solid Tumors, version 1.1. Secondary end points included disease control rate, duration of response, progression-free survival, overall survival, and safety. RESULTS: The pooled data set included 225 patients (n = 138 in NP28673 and n = 87 in NP28761). The response-evaluable population included 189 patients (84% [n = 122 in NP28673 and n = 67 in NP28761]). In the response-evaluable population, objective response rate as assessed by the IRC was 51.3% (95% confidence interval [CI]: 44.0-58.6 [all PRs]), the disease control rate was 78.8% (95% CI: 72.3-84.4), and the median duration of response was 14.9 months (95% CI: 11.1-20.4) after 58% of events. Median progression-free survival as assessed by the IRC was 8.3 months (95% CI: 7.0-11.3) and median overall survival was 26.0 months (95% CI: 21.4-not estimable). Grade 3 or higher adverse events (AEs) occurred in 40% of patients, 6% of patients had treatment withdrawn on account of AEs, and 33% had AEs leading to dose interruptions/modification. CONCLUSIONS: This pooled data analysis confirmed the robust systemic efficacy of alectinib in ALK-positive NSCLC with a durable response rate. Alectinib also had an acceptable safety profile with a longer duration of follow-up. CI - Copyright (c) 2017 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved. FAU - Yang, James Chih-Hsin AU - Yang JC AD - Department of Oncology, National Taiwan University Hospital and National Taiwan University Cancer Centre, Taipei, Taiwan. Electronic address: chihyang@ntu.edu.tw. FAU - Ou, Sai-Hong Ignatius AU - Ou SI AD - Chao Family Comprehensive Cancer Centre, University of California Irvine School of Medicine, Orange, California. FAU - De Petris, Luigi AU - De Petris L AD - Oncology, Karolinska University Hospital, Stockholm, Sweden. FAU - Gadgeel, Shirish AU - Gadgeel S AD - Karmanos Cancer Institute, Wayne State University, Detroit, Michigan. FAU - Gandhi, Leena AU - Gandhi L AD - New York University, Perlmutter Cancer Center, New York University School of Medicine, New York, New York. FAU - Kim, Dong-Wan AU - Kim DW AD - Seoul National University Hospital, Seoul, Republic of Korea. FAU - Barlesi, Fabrice AU - Barlesi F AD - Aix Marseille University; Assistance Publique Hopitaux de Marseille, Marseille, France. FAU - Govindan, Ramaswamy AU - Govindan R AD - Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri. FAU - Dingemans, Anne-Marie C AU - Dingemans AC AD - Maastricht University Medical Centre, Maastricht, The Netherlands. FAU - Crino, Lucio AU - Crino L AD - Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori, Istituto di Ricovero e Cura a Carattere Scientifico, Meloda, Italy. FAU - Lena, Herve AU - Lena H AD - Centre Hospitalier Universitaire, Rennes University, Rennes, France. FAU - Popat, Sanjay AU - Popat S AD - Royal Marsden Hospital, London, United Kingdom. FAU - Ahn, Jin Seok AU - Ahn JS AD - Samsung Medical Centre, Seoul, Republic of Korea. FAU - Dansin, Eric AU - Dansin E AD - Centre Regional de Lutte Contre le Cancer Oscar-Lambret, Lille, France. FAU - Golding, Sophie AU - Golding S AD - F. Hoffmann-La Roche Ltd., Basel, Switzerland. FAU - Bordogna, Walter AU - Bordogna W AD - F. Hoffmann-La Roche Ltd., Basel, Switzerland. FAU - Balas, Bogdana AU - Balas B AD - F. Hoffmann-La Roche Ltd., Basel, Switzerland. FAU - Morcos, Peter N AU - Morcos PN AD - F. Hoffmann-La Roche, Innovation Center, New York, New York. FAU - Zeaiter, Ali AU - Zeaiter A AD - F. Hoffmann-La Roche Ltd., Basel, Switzerland. FAU - Shaw, Alice T AU - Shaw AT AD - Massachusetts General Hospital Cancer Centre, Harvard Medical School, Boston, Massachusetts. LA - eng GR - P30 CA022453/CA/NCI NIH HHS/United States PT - Clinical Trial, Phase II PT - Journal Article PT - Multicenter Study DEP - 20170706 PL - United States TA - J Thorac Oncol JT - Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer JID - 101274235 RN - 0 (Carbazoles) RN - 0 (Piperidines) RN - LIJ4CT1Z3Y (alectinib) SB - IM MH - Adult MH - Aged MH - Carbazoles/pharmacology/*therapeutic use MH - Carcinoma, Non-Small-Cell Lung/*drug therapy/pathology MH - Female MH - Humans MH - Lung Neoplasms/*drug therapy/pathology MH - Male MH - Middle Aged MH - Piperidines/pharmacology/*therapeutic use MH - Treatment Outcome PMC - PMC6886236 MID - NIHMS1060537 OTO - NOTNLM OT - Alectinib OT - NP28673 OT - NP28761 OT - Non-small cell lung cancer OT - Pooled analysis COIS- Disclosure: Dr. Yang has received advisory board fees from Boehringer Ingelheim, Bayer, AstraZeneca, Roche/Genentech, Chugai, Clovis Oncology, Eli Lilly, Merck Sharp and Dohme, Merck Serono, Pfizer, Novartis, Celgene, Merrimack, Yuhan Pharmaceuticals, and Daiichi Sankyo. Dr. Ou has received personal fees for Pfizer, AstraZeneca, ARIAD, and Roche outside the submitted work. Dr. De Petris has received personal fees from Roche, AstraZeneca, and Bristol-Myers Squibb. Dr. Gadgeel has received consultancy fees from Boehringer Ingelheim, ARIAD, Novartis, and Genentech. Dr. Gandhi has received consultancy fees from Genentech/Roche, Pfizer, Merck, Abbvie, and AstraZeneca and personal fees from Merck and Bristol-Myers Squibb IION Foundation. Dr. Kim has received personal fees from Roche. Dr. Barlesi has received consulting fees from Roche. Dr. Govindan has received travel accommodation fees and consulting fees from Merck, Boehringer Ingelheim, Celgene, Roche, Stemcentrix, and Abbe Vie and consultancy fees from GlaxoSmithKline, Clovis, and Helsinn Healthcare. Dr. Dingemans has received consultancy fees from Eli Lilly, AstraZeneca, Clovis, Boehringer Ingelheim, and Merck Sharp and Dohme. Dr. Lena reports advisory board membership for Roche, Merck Sharp and Dohme, Bristol-Myers Squibb, Novartis, Pfizer, and AstraZeneca and has been reimbursed for meeting expenses from Roche, Merck Sharp and Dohme, Bristol-Myers Squibb, Lilly, and Amgen. Dr. Popat has received personal fees from Roche, Pfizer, and Novartis outside the submitted work. Dr. Dansin has received personal fees from Bristol-Myers Squibb, AstraZeneca, and Roche. Ms. Golding, Dr. Bordogna, Dr. Balas, Mr. Morcos, and Dr. Zeaiter are employees of and have stock ownership in Roche. Dr. Shaw has received consulting fees from Ignyta and Taiho and advisory board fees from Pfizer, Novartis, Genentech/Roche, Ariad, Daiichi-Sankyo, Blueprint Medicines, Loxo, EMD Serono, and Foundation Medicine. The remaining authors declare no conflict of interest. EDAT- 2017/07/10 06:00 MHDA- 2018/06/12 06:00 PMCR- 2019/12/02 CRDT- 2017/07/10 06:00 PHST- 2017/05/22 00:00 [received] PHST- 2017/06/27 00:00 [revised] PHST- 2017/06/29 00:00 [accepted] PHST- 2017/07/10 06:00 [pubmed] PHST- 2018/06/12 06:00 [medline] PHST- 2017/07/10 06:00 [entrez] PHST- 2019/12/02 00:00 [pmc-release] AID - S1556-0864(17)30570-1 [pii] AID - 10.1016/j.jtho.2017.06.070 [doi] PST - ppublish SO - J Thorac Oncol. 2017 Oct;12(10):1552-1560. doi: 10.1016/j.jtho.2017.06.070. Epub 2017 Jul 6.