PMID- 36375271 OWN - NLM STAT- MEDLINE DCOM- 20221227 LR - 20230103 IS - 2059-7029 (Electronic) IS - 2059-7029 (Linking) VI - 7 IP - 6 DP - 2022 Dec TI - Clinical experience and management of adverse events in patients with advanced ALK-positive non-small-cell lung cancer receiving alectinib. PG - 100612 LID - S2059-7029(22)00243-5 [pii] LID - 10.1016/j.esmoop.2022.100612 [doi] LID - 100612 AB - Alectinib is a preferred first-line therapy for patients with advanced anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancer (NSCLC) in several national clinical practice guidelines. The randomized, global, phase III ALEX study has demonstrated significant improvement in progression-free survival for alectinib over crizotinib in treatment-naive ALK-positive NSCLC. It was also the first study to show clinically meaningful improvement in overall survival for a next-generation ALK tyrosine kinase inhibitor relative to crizotinib. The J-ALEX and ALESIA phase III studies confirmed the clinical benefit of alectinib relative to crizotinib in the first-line ALK-positive NSCLC treatment setting in Japanese and Asian patients, respectively. Across these pivotal phase III trials, alectinib had a manageable, well-characterized safety profile. Here, we review the safety and tolerability of long-term alectinib treatment in patients with advanced ALK-positive NSCLC and provide guidance for physicians, based on clinical experience, on the management of the most frequently reported adverse events (AEs). Most AEs associated with alectinib can be managed by dose reduction. Some alectinib-related AEs are not yet fully characterized, including myalgia and peripheral oedema and deciphering their underlying mechanism of action could enhance their management. With longer-term follow-up, the safety profile of alectinib continues to remain consistent in the ALEX study, with no new safety signals observed. Safety and tolerability data from the first-line phase III alectinib trials are also consistent with those observed in clinical trials of alectinib in later-line settings. These results add to the weight of evidence recommending alectinib as a preferred therapy for treatment-naive advanced ALK-positive NSCLC. CI - Copyright (c) 2022 The Authors. Published by Elsevier Ltd.. All rights reserved. FAU - Dziadziuszko, R AU - Dziadziuszko R AD - Department of Oncology and Radiotherapy, Medical University of Gdansk, Gdansk, Poland. FAU - Peters, S AU - Peters S AD - Lausanne University Hospital, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland. FAU - Ruf, T AU - Ruf T AD - F. Hoffmann-La Roche Ltd., Basel, Switzerland. FAU - Cardona, A AU - Cardona A AD - F. Hoffmann-La Roche Ltd., Basel, Switzerland. FAU - Guerini, E AU - Guerini E AD - F. Hoffmann-La Roche Ltd., Basel, Switzerland. FAU - Kurtsikidze, N AU - Kurtsikidze N AD - F. Hoffmann-La Roche Ltd., Basel, Switzerland. FAU - Smoljanovic, V AU - Smoljanovic V AD - F. Hoffmann-La Roche Ltd., Basel, Switzerland. FAU - Planchard, D AU - Planchard D AD - Department of Medical Oncology, Thoracic Oncology Unit, Gustave Roussy Cancer Campus, Villejuif, France. Electronic address: david.planchard@gustaveroussy.fr. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review DEP - 20221111 PL - England TA - ESMO Open JT - ESMO open JID - 101690685 RN - LIJ4CT1Z3Y (alectinib) RN - 53AH36668S (Crizotinib) RN - EC 2.7.10.1 (Anaplastic Lymphoma Kinase) RN - 0 (Protein Kinase Inhibitors) RN - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases) SB - IM MH - Humans MH - *Carcinoma, Non-Small-Cell Lung/drug therapy/pathology MH - Crizotinib/therapeutic use MH - *Lung Neoplasms/pathology MH - Anaplastic Lymphoma Kinase MH - Protein Kinase Inhibitors/adverse effects MH - Receptor Protein-Tyrosine Kinases/therapeutic use PMC - PMC9663323 OTO - NOTNLM OT - ALK-positive NSCLC OT - alectinib OT - clinical experience OT - safety OT - tolerability COIS- Disclosure RD has received honoraria or consulting fees from Roche, AstraZeneca, Pfizer, Novartis, Takeda, Bristol Myers Squibb, Boehringer Ingelheim, Merck Sharp & Dohme, Foundation Medicine, Regeneron, Seattle Genetics, Karyopharm and Bayer. SP has received educational grants, provided consultation, attended advisory boards, and/or provided lectures for AbbVie, Amgen, AstraZeneca, Bayer, BeiGene, Biocartis, Boehringer Ingelheim, Bristol Myers Squibb, Clovis Oncology, Daiichi Sankyo, Debiopharm, ecancer, Eli Lilly, Elsevier, F. Hoffmann-La Roche Ltd/Genentech, Fishawack, Foundation Medicine, Illumina, Imedex, IQVIA, Incyte, Janssen, Medscape, Merck Sharp & Dohme, Merck Serono, Merrimack, Novartis, OncologyEducation, Pharma Mar, Phosplatin Therapeutics, PER, Pfizer, PRIME, Regeneron, RMEI, RTP, Sanofi, Seattle Genetics and Takeda, from whom she has received honoraria; and received grants or research support [(sub)investigator in trials (institutional financial support for clinical trials)] from Amgen, AstraZeneca, Biodesix, Boehringer Ingelheim, Bristol Myers Squibb, Clovis Oncology, F. Hoffmann-La Roche Ltd/Genentech, GlaxoSmithKline, Illumina, Lilly, Merck Sharp & Dohme, Merck Serono, Mirati, Novartis, Pfizer, and Phosplatin Therapeutics. TR, AC, EG, NK and VS are employees of F. Hoffmann-La Roche Ltd. DP reports personal fees, non-financial support and other from AstraZeneca, AbbVie, Bayer, Bristol Myers Squibb, Celgene, Daiichi Sankyo, Merck, Novartis, Pfizer, Roche, MedImmune, Sanofi-Aventis, Janssen and Samsung outside the submitted work. Data sharing For eligible studies qualified researchers may request access to individual patient level clinical data through a data request platform. At the time of writing this request platform is Vivli. https://vivli.org/ourmember/roche/. For up to date details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here: https://go.roche.com/data_sharing. Anonymised records for individual patients across more than one data source external to Roche cannot, and should not, be linked due to a potential increase in risk of patient re-identification. EDAT- 2022/11/15 06:00 MHDA- 2022/12/28 06:00 PMCR- 2022/11/11 CRDT- 2022/11/14 18:18 PHST- 2022/02/10 00:00 [received] PHST- 2022/09/22 00:00 [revised] PHST- 2022/09/27 00:00 [accepted] PHST- 2022/11/15 06:00 [pubmed] PHST- 2022/12/28 06:00 [medline] PHST- 2022/11/14 18:18 [entrez] PHST- 2022/11/11 00:00 [pmc-release] AID - S2059-7029(22)00243-5 [pii] AID - 100612 [pii] AID - 10.1016/j.esmoop.2022.100612 [doi] PST - ppublish SO - ESMO Open. 2022 Dec;7(6):100612. doi: 10.1016/j.esmoop.2022.100612. Epub 2022 Nov 11.