PMID- 31959349 OWN - NLM STAT- MEDLINE DCOM- 20210106 LR - 20220531 IS - 1569-8041 (Electronic) IS - 0923-7534 (Linking) VI - 31 IP - 2 DP - 2020 Feb TI - Safety and patient-reported outcomes of atezolizumab, carboplatin, and etoposide in extensive-stage small-cell lung cancer (IMpower133): a randomized phase I/III trial. PG - 310-317 LID - S0923-7534(19)36078-8 [pii] LID - 10.1016/j.annonc.2019.10.021 [doi] AB - BACKGROUND: The addition of atezolizumab to carboplatin and etoposide (CP/ET) significantly improved progression-free and overall survival for patients with extensive-stage small-cell lung cancer (ES-SCLC) in the IMpower133 study (NCT02763579). We have evaluated adverse events (AEs) and patient-reported outcomes in IMpower133 to assess the benefit-risk profile of this regimen. PATIENTS AND METHODS: Patients received four 21-day cycles of CP/ET plus intravenous atezolizumab 1200 mg or placebo (induction phase), followed by atezolizumab or placebo (maintenance phase) until progression or loss of benefit. AEs were assessed and patient-reported outcomes were evaluated every 3 weeks during treatment using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 (QLQ-C30) and QLQ-LC13. RESULTS: Overall, 394 patients were assessable for safety in the induction phase and 318 in the maintenance phase. The frequency of AEs, grade 3-4 AEs, and serious AEs was similar between arms in both phases. Immune-related AEs were more frequent in the atezolizumab arm during both induction (28% versus 17%; leading to atezolizumab/placebo interruption 9% versus 5%, leading to withdrawal 4% versus 0%) and maintenance (26% versus 15%; leading to atezolizumab/placebo interruption, 3% versus 2%, leading to withdrawal 1% versus 1%), most commonly rash (induction 11% versus 9%, maintenance 14% versus 4%), and hypothyroidism (induction 4.0% versus 0%, maintenance 10% versus 1%). Changes in patient-reported treatment-related symptoms commonly associated with quality of life impairment were generally similar during induction and most of the maintenance phase. Patient-reported function and health-related quality of life (HRQoL) improved in both arms after initiating treatment, with more pronounced and persistent HRQoL improvements in the atezolizumab arm. CONCLUSIONS: In patients with ES-SCLC, atezolizumab plus CP/ET has a comparable safety profile to placebo plus CP/ET, and the addition of atezolizumab did not adversely impact patient-reported HRQoL. These data demonstrate the positive benefit-risk profile of first-line atezolizumab plus CP/ET in ES-SCLC and further support this regimen as a new standard of care in this setting. CLINICAL TRIALS NUMBER: NCT02763579. CI - Copyright (c) 2019 The Authors. Published by Elsevier Ltd.. All rights reserved. FAU - Mansfield, A S AU - Mansfield AS AD - Division of Medical Oncology, Mayo Clinic, Rochester, USA. Electronic address: Mansfield.Aaron@mayo.edu. FAU - Kazarnowicz, A AU - Kazarnowicz A AD - Department of Oncology, Tuberculosis and Lung Disease Hospital, Olsztyn, Poland. FAU - Karaseva, N AU - Karaseva N AD - City Clinical Oncology Dispensary, St Petersburg, Russia. FAU - Sanchez, A AU - Sanchez A AD - Department of Medical Oncology, Hospital Universitario "Virgen del Rocio", Seville, Spain. FAU - De Boer, R AU - De Boer R AD - Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia. FAU - Andric, Z AU - Andric Z AD - Department of Medical Oncology, University Hospital Medical Center Bezanijska Kosa, Belgrade, Serbia. FAU - Reck, M AU - Reck M AD - Department of Thoracic Oncology, German Center for Lung Research (DZL), Grosshansdorf, Germany. FAU - Atagi, S AU - Atagi S AD - Department of Thoracic Oncology, Kinki-Chuo Chest Medical Center, Osaka, Japan. FAU - Lee, J-S AU - Lee JS AD - Division of Hematology-Oncology, Seoul National University Bundang Hospital, Seongnam, Republic of Korea. FAU - Garassino, M AU - Garassino M AD - Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. FAU - Liu, S V AU - Liu SV AD - Georgetown Lombardi Comprehensive Cancer Center, Georgetown University, Washington DC, USA. FAU - Horn, L AU - Horn L AD - Thoracic Oncology Program, Vanderbilt University Medical Center, Nashville, USA. FAU - Wen, X AU - Wen X AD - Product Development Oncology, Genentech, Inc., South San Francisco, USA. FAU - Quach, C AU - Quach C AD - Product Development Oncology, Genentech, Inc., South San Francisco, USA. FAU - Yu, W AU - Yu W AD - Biometrics, Genentech, Inc., South San Francisco, USA. FAU - Kabbinavar, F AU - Kabbinavar F AD - Product Development Oncology, Genentech, Inc., South San Francisco, USA. FAU - Lam, S AU - Lam S AD - Product Development Oncology, Genentech, Inc., South San Francisco, USA. FAU - Morris, S AU - Morris S AD - Global PD Medical Affairs (Oncology), F. Hoffmann-La Roche Ltd, Basel, Switzerland. FAU - Califano, R AU - Califano R AD - Department of Medical Oncology, The Christie NHS Foundation Trust, and Division of Cancer Sciences, University of Manchester, Manchester, UK. LA - eng SI - ClinicalTrials.gov/NCT02763579 PT - Clinical Trial, Phase I PT - Clinical Trial, Phase III PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20191209 PL - England TA - Ann Oncol JT - Annals of oncology : official journal of the European Society for Medical Oncology JID - 9007735 RN - 0 (Antibodies, Monoclonal, Humanized) RN - 52CMI0WC3Y (atezolizumab) RN - 6PLQ3CP4P3 (Etoposide) RN - BG3F62OND5 (Carboplatin) SB - IM MH - Antibodies, Monoclonal, Humanized MH - Antineoplastic Combined Chemotherapy Protocols/adverse effects MH - Carboplatin/adverse effects MH - Etoposide/therapeutic use MH - Humans MH - *Lung Neoplasms/drug therapy MH - Patient Reported Outcome Measures MH - *Quality of Life OTO - NOTNLM OT - PD-L1 OT - TECENTRIQ OT - atezolizumab OT - extensive-stage small-cell lung cancer OT - quality of life OT - safety EDAT- 2020/01/22 06:00 MHDA- 2021/01/07 06:00 CRDT- 2020/01/22 06:00 PHST- 2019/07/01 00:00 [received] PHST- 2019/09/27 00:00 [revised] PHST- 2019/10/20 00:00 [accepted] PHST- 2020/01/22 06:00 [entrez] PHST- 2020/01/22 06:00 [pubmed] PHST- 2021/01/07 06:00 [medline] AID - S0923-7534(19)36078-8 [pii] AID - 10.1016/j.annonc.2019.10.021 [doi] PST - ppublish SO - Ann Oncol. 2020 Feb;31(2):310-317. doi: 10.1016/j.annonc.2019.10.021. Epub 2019 Dec 9.