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Efficacy of PD-(L)1 blockade monotherapy compared with PD-(L)1 blockade plus chemotherapy in first-line PD-L1-positive advanced lung adenocarcinomas: a cohort study.

التفاصيل البيبلوغرافية
العنوان: Efficacy of PD-(L)1 blockade monotherapy compared with PD-(L)1 blockade plus chemotherapy in first-line PD-L1-positive advanced lung adenocarcinomas: a cohort study.
المؤلفون: Elkrief A; Department of Medicine, Thoracic Oncology Service, Memorial Sloan Kettering Cancer Center, New York, New York, USA.; Human Oncology & Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York, USA.; Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Alessi JMV; Lowe Center for Thoracic Oncology, Dana Farber Cancer Institute, Boston, Massachusetts, USA., Ricciuti B; Lowe Center for Thoracic Oncology, Dana Farber Cancer Institute, Boston, Massachusetts, USA., Brown S; Department of Epidemiology & Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York, USA., Rizvi H; Department of Medicine, Thoracic Oncology Service, Memorial Sloan Kettering Cancer Center, New York, New York, USA., Preeshagul IR; Department of Medicine, Thoracic Oncology Service, Memorial Sloan Kettering Cancer Center, New York, New York, USA., Wang X; Environmental Health, Harvard University, Boston, Massachusetts, USA., Pecci F; Lowe Center for Thoracic Oncology, Dana Farber Cancer Institute, Boston, Massachusetts, USA., Di Federico A; Lowe Center for Thoracic Oncology, Dana Farber Cancer Institute, Boston, Massachusetts, USA., Lamberti G; Lowe Center for Thoracic Oncology, Dana Farber Cancer Institute, Boston, Massachusetts, USA., Egger JV; Department of Medicine, Thoracic Oncology Service, Memorial Sloan Kettering Cancer Center, New York, New York, USA., Chaft JE; Department of Medicine, Thoracic Oncology Service, Memorial Sloan Kettering Cancer Center, New York, New York, USA.; Weill Cornell Medical College, New York, New York, USA., Rudin CM; Department of Medicine, Thoracic Oncology Service, Memorial Sloan Kettering Cancer Center, New York, New York, USA.; Weill Cornell Medical College, New York, New York, USA., Riely GJ; Department of Medicine, Thoracic Oncology Service, Memorial Sloan Kettering Cancer Center, New York, New York, USA.; Weill Cornell Medical College, New York, New York, USA., Kris MG; Department of Medicine, Thoracic Oncology Service, Memorial Sloan Kettering Cancer Center, New York, New York, USA.; Weill Cornell Medical College, New York, New York, USA., Ladanyi M; Human Oncology & Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York, USA.; Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Chen Y; Department of Epidemiology & Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York, USA., Hellmann MD; Department of Medicine, Thoracic Oncology Service, Memorial Sloan Kettering Cancer Center, New York, New York, USA.; Weill Cornell Medical College, New York, New York, USA., Shen R; Department of Epidemiology & Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York, USA., Awad MM; Lowe Center for Thoracic Oncology, Dana Farber Cancer Institute, Boston, Massachusetts, USA., Schoenfeld AJ; Department of Medicine, Thoracic Oncology Service, Memorial Sloan Kettering Cancer Center, New York, New York, USA schoenfa@mskcc.org.; Weill Cornell Medical College, New York, New York, USA.
المصدر: Journal for immunotherapy of cancer [J Immunother Cancer] 2023 Jul; Vol. 11 (7).
نوع المنشور: Multicenter Study; Journal Article; Research Support, N.I.H., Extramural
اللغة: English
بيانات الدورية: Publisher: BMJ Publishing Group Ltd Country of Publication: England NLM ID: 101620585 Publication Model: Print Cited Medium: Internet ISSN: 2051-1426 (Electronic) Linking ISSN: 20511426 NLM ISO Abbreviation: J Immunother Cancer Subsets: MEDLINE
أسماء مطبوعة: Publication: 2020- : London, United Kingdom : BMJ Publishing Group Ltd.
Original Publication: London : BioMed Central, 2013-
مواضيع طبية MeSH: Adenocarcinoma of Lung* , Lung Neoplasms*, Humans ; Cohort Studies ; B7-H1 Antigen ; Retrospective Studies
مستخلص: Background: Single-agent PD-(L)1 blockade (IO) alone or in combination with chemotherapy (Chemotherapy-IO) is approved first-line therapies in patients with advanced lung adenocarcinomas (LUADs) with PD-L1 expression ≥1%. These regimens have not been compared prospectively. The primary objective was to compare first-line efficacies of single-agent IO to Chemotherapy-IO in patients with advanced LUADs. Secondary objectives were to explore if clinical, pathological, and genomic features were associated with differential response to Chemotherapy-IO versus IO.
Methods: This was a multicenter retrospective cohort study. Inclusion criteria were patients with advanced LUADs with tumor PD-L1 ≥1% treated with first-line Chemotherapy-IO or IO. To compare the first-line efficacies of single-agent IO to Chemotherapy-IO, we conducted inverse probability weighted Cox proportional hazards models using estimated propensity scores.
Results: The cohort analyzed included 866 patients. Relative to IO, Chemotherapy-IO was associated with improved objective response rate (ORR) (44% vs 35%, p=0.007) and progression-free survival (PFS) in patients with tumor PD-L1≥1% (HR 0.84, 95% CI 0.72 to 0.97, p=0.021) or PD-L1≥50% (ORR 55% vs 38%, p<0.001; PFS HR 0.68, 95% CI 0.53 to 0.87, p=0.002). Using propensity-adjusted analyses, only never-smokers in the PD-L1≥50% subgroup derived a differential survival benefit from Chemotherapy-IO vs IO (p=0.013). Among patients with very high tumor PD-L1 expression (≥90%), there were no differences in outcome between treatment groups. No genomic factors conferred differential survival benefit to Chemotherapy-IO versus IO.
Conclusions: While the addition of chemotherapy to PD-(L)1 blockade increases the probability of initial response, never-smokers with tumor PD-L1≥50% comprise the only population identified that derived an apparent survival benefit with treatment intensification.
Competing Interests: Competing interests: JEC has consulted for: AstraZeneca, BMS, Genentech, Merck, Flame Biosciences, Regeneron-Sanofi, Guardant Health, Arcus Biosciences and also declared research funding to institution from: AstraZeneca, BMS, Genentech, Merck, Novartis. CMR has consulted with AbbVie, Amgen, Astra Zeneca, D2G, Daiichi Sankyo, Epizyme, Genentech/Roche, Ipsen, Jazz, Kowa, Lilly, Merck, and Syros. He serves on the scientific advisory boards of Bridge Medicines, Earli, and Harpoon Therapeutics. GJR reports institutional research support from Mirati, Lilly, Takeda, Merck, Roche, Pfizer, and Novartis. MGK reports honoraria from AstraZeneca, Pfizer, Merus, and BerGenBio. MDH reports grants from BMS; and personal fees from Achilles; Adagene; Adicet; Arcus; AstraZeneca; Blueprint; BMS; DaVolterra; Eli Lilly; Genentech/Roche; Genzyme/Sanofi; Janssen; Immunai; Instil Bio; Mana Therapeutics; Merck; Mirati; Natera; Pact Pharma; Shattuck Labs; and Regeneron; as well as equity options from Factorial, Immunai, Shattuck Labs, Arcus, and Avail Bio. A patent filed by Memorial Sloan Kettering related to the use of tumor mutational burden to predict response to immunotherapy (PCT/US2015/062208) is pending and licensed by PGDx. Subsequent to the completion of this work, MDH began as an employee (and equity holder) at AstraZeneca. MA reports that he was a consultant to: Bristol-Myers Squibb, Merck, Genentech, AstraZeneca, Mirati, Novartis, Blueprint Medicine, Abbvie, Gritstone, NextCure, EMD Serono and received research funding (to institute) from: Bristol-Myers Squibb, Eli Lilly, Genentech, AstraZeneca, Amgen. AS reports consulting/advising role to J&J, KSQ therapeutics, BMS, Merck, Enara Bio, Perceptive Advisors, Oppenheimer and Co, Umoja Biopharma, Legend Biotech, Iovance Biotherapeutics, Lyell Immunopharma and Heat Biologics, research funding from GSK (Inst), PACT pharma (Inst), Iovance Biotherapeutics (Inst), Achilles therapeutics (Inst), Merck (Inst), BMS (Inst), Harpoon Therapeutics (Inst) and Amgen (Inst). AS reports consulting/advising role to J&J, KSQ therapeutics, BMS, Merck, Enara Bio, Perceptive Advisors, Oppenheimer and Co, Umoja Biopharma, Legend Biotech, Iovance Biotherapeutics, Lyell Immunopharma and Heat Biologics. Research funding: GSK (Inst), PACT pharma (Inst), Iovance Biotherapeutics (Inst), Achilles therapeutics (Inst), Merck (Inst), BMS (Inst), Harpoon Therapeutics (Inst) and Amgen (Inst).
(© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
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معلومات مُعتمدة: P30 CA008748 United States CA NCI NIH HHS; U01 CA209414 United States CA NCI NIH HHS
فهرسة مساهمة: Keywords: Combined Modality Therapy; Genetic Markers; Immune Checkpoint Inhibitors; Non-Small Cell Lung Cancer
المشرفين على المادة: 0 (B7-H1 Antigen)
تواريخ الأحداث: Date Created: 20230724 Date Completed: 20230726 Latest Revision: 20230729
رمز التحديث: 20230729
مُعرف محوري في PubMed: PMC10373730
DOI: 10.1136/jitc-2023-006994
PMID: 37487667
قاعدة البيانات: MEDLINE
الوصف
تدمد:2051-1426
DOI:10.1136/jitc-2023-006994