دورية أكاديمية
Association of Immune-Related Adverse Events With Efficacy of Atezolizumab in Patients With Non-Small Cell Lung Cancer: Pooled Analyses of the Phase 3 IMpower130, IMpower132, and IMpower150 Randomized Clinical Trials.
| العنوان: | Association of Immune-Related Adverse Events With Efficacy of Atezolizumab in Patients With Non-Small Cell Lung Cancer: Pooled Analyses of the Phase 3 IMpower130, IMpower132, and IMpower150 Randomized Clinical Trials. |
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| المؤلفون: | Socinski MA; AdventHealth Cancer Institute, Orlando, Florida., Jotte RM; Rocky Mountain Cancer Centers, Denver, Colorado.; US Oncology, Houston, Texas., Cappuzzo F; Istituto Nazionale Tumori IRCCS Regina Elena, Roma, Italy., Nishio M; The Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan., Mok TSK; State Key Laboratory of Translational Oncology, The Chinese University of Hong Kong, Hong Kong., Reck M; Lung Clinic Grosshansdorf, Airway Research Center North, German Center for Lung Research, Grosshansdorf, Germany., Finley GG; Allegheny Health Network Cancer Institute, Pittsburgh, Pennsylvania., Kaul MD; Genentech, Inc, South San Francisco, California., Yu W; Genentech, Inc, South San Francisco, California., Paranthaman N; Genentech, Inc, South San Francisco, California., Bara I; Genentech, Inc, South San Francisco, California., West HJ; City of Hope Comprehensive Cancer Center, Duarte, California. |
| المصدر: | JAMA oncology [JAMA Oncol] 2023 Apr 01; Vol. 9 (4), pp. 527-535. |
| نوع المنشور: | Multicenter Study; Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Medical Association Country of Publication: United States NLM ID: 101652861 Publication Model: Print Cited Medium: Internet ISSN: 2374-2445 (Electronic) Linking ISSN: 23742437 NLM ISO Abbreviation: JAMA Oncol Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Chicago, Il : American Medical Association, [2015]- |
| مواضيع طبية MeSH: | Carcinoma, Non-Small-Cell Lung*/drug therapy , Lung Neoplasms*, Adult ; Humans ; Male ; Middle Aged ; Female ; Bevacizumab/therapeutic use ; Carboplatin/adverse effects ; Randomized Controlled Trials as Topic ; Paclitaxel/adverse effects ; Antineoplastic Combined Chemotherapy Protocols/adverse effects |
| مستخلص: | Importance: Immune-related adverse events (irAEs) arising from immune checkpoint inhibitor (ICI) cancer therapy may potentially predict improved outcomes. Objective: To evaluate the association between irAEs and atezolizumab efficacy in patients with advanced non-small cell lung cancer (NSCLC) using pooled data from 3 phase 3 ICI studies. Design, Setting, and Participants: IMpower130, IMpower132, and IMpower150 were phase 3, multicenter, open-label, randomized clinical trials to evaluate the efficacy and safety of chemoimmunotherapy combinations involving atezolizumab. Participants were chemotherapy-naive adults with stage IV nonsquamous NSCLC. These post hoc analyses were conducted during February 2022. Interventions: Eligible patients were randomly assigned 2:1 to receive atezolizumab with carboplatin plus nab-paclitaxel, or chemotherapy alone (IMpower130); 1:1 to receive atezolizumab with carboplatin or cisplatin plus pemetrexed, or chemotherapy alone (IMpower132); and 1:1:1 to receive atezolizumab plus bevacizumab plus carboplatin and paclitaxel, atezolizumab plus carboplatin and paclitaxel, or bevacizumab plus carboplatin and paclitaxel (IMpower150). Main Outcomes and Measures: Pooled data from IMpower130 (cutoff: March 15, 2018), IMpower132 (cutoff: May 22, 2018), and IMpower150 (cutoff: September 13, 2019) were analyzed by treatment (atezolizumab-containing vs control), irAE status (with vs without), and highest irAE grade (1-2 vs 3-5). To account for immortal bias, a time-dependent Cox model and landmark analyses of irAE occurrence at 1, 3, 6, and 12 months from baseline were used to estimate the hazard ratio (HR) of overall survival (OS). Results: Of 2503 randomized patients, 1577 were in the atezolizumab-containing arm and 926 were in the control arm. The mean (SD) age of patients was 63.1 (9.4) years and 63.0 (9.3) years, and 950 (60.2%) and 569 (61.4%) were male, respectively, in the atezolizumab arm and the control arm. Baseline characteristics were generally balanced between patients with irAEs (atezolizumab, n = 753; control, n = 289) and without (atezolizumab, n = 824; control, n = 637). In the atezolizumab arm, OS HRs (95% CI) in patients with grade 1 to 2 irAEs and grade 3 to 5 irAEs (each vs those without irAEs) in the 1-, 3-, 6-, and 12-month subgroups were 0.78 (0.65-0.94) and 1.25 (0.90-1.72), 0.74 (0.63-0.87) and 1.23 (0.93-1.64), 0.77 (0.65-0.90) and 1.1 (0.81-1.42), and 0.72 (0.59-0.89) and 0.87 (0.61-1.25), respectively. Conclusions and Relevance: In this pooled analysis of 3 randomized clinical trials, longer OS was observed in patients with vs without mild to moderate irAEs in both arms and across landmarks. These findings further support the use of first-line atezolizumab-containing regimens for advanced nonsquamous NSCLC. Trial Registration: ClinicalTrials.gov Identifiers: NCT02367781, NCT02657434, and NCT02366143. |
| التعليقات: | Erratum in: JAMA Oncol. 2023 Apr 1;9(4):574. (PMID: 37078994) |
| سلسلة جزيئية: | ClinicalTrials.gov NCT02366143; NCT02367781; NCT02657434 |
| المشرفين على المادة: | 52CMI0WC3Y (atezolizumab) 2S9ZZM9Q9V (Bevacizumab) BG3F62OND5 (Carboplatin) P88XT4IS4D (Paclitaxel) |
| تواريخ الأحداث: | Date Created: 20230216 Date Completed: 20230424 Latest Revision: 20230504 |
| رمز التحديث: | 20230504 |
| مُعرف محوري في PubMed: | PMC9936386 |
| DOI: | 10.1001/jamaoncol.2022.7711 |
| PMID: | 36795388 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 2374-2445 |
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| DOI: | 10.1001/jamaoncol.2022.7711 |