دورية أكاديمية
Outcomes of Combination Platinum-Doublet Chemotherapy and Anti-PD(L)-1 Blockade in KRASG12C-Mutant Non-Small Cell Lung Cancer.
| العنوان: | Outcomes of Combination Platinum-Doublet Chemotherapy and Anti-PD(L)-1 Blockade in KRASG12C-Mutant Non-Small Cell Lung Cancer. |
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| المؤلفون: | Elkrief A; Department of Medicine, Thoracic Oncology Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA.; Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.; Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Riccuiti B; Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, Boston, MA, USA., Alessi JV; Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, Boston, MA, USA., Fei T; Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Kalvin HL; Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Egger JV; Department of Medicine, Thoracic Oncology Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Rizvi H; Department of Medicine, Thoracic Oncology Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Thummalapalli R; Department of Medicine, Thoracic Oncology Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Lamberti G; Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, Boston, MA, USA., Plodkowski A; Department of Medicine, Thoracic Oncology Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Hellmann MD; Department of Medicine, Thoracic Oncology Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA.; Department of Medicine, Weill Cornell Medical College, New York, NY, USA., Kris MG; Department of Medicine, Thoracic Oncology Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA.; Department of Medicine, Weill Cornell Medical College, New York, NY, USA., Arcila ME; Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Baine MK; Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Rudin CM; Department of Medicine, Thoracic Oncology Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA.; Department of Medicine, Weill Cornell Medical College, New York, NY, USA., Lito P; Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.; Department of Medicine, Weill Cornell Medical College, New York, NY, USA., Ladanyi M; Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.; Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Schoenfeld AJ; Department of Medicine, Thoracic Oncology Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA.; Department of Medicine, Weill Cornell Medical College, New York, NY, USA., Riely GJ; Department of Medicine, Thoracic Oncology Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA.; Department of Medicine, Weill Cornell Medical College, New York, NY, USA., Awad MM; Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, Boston, MA, USA., Arbour KC; Department of Medicine, Thoracic Oncology Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA.; Department of Medicine, Weill Cornell Medical College, New York, NY, USA. |
| المصدر: | The oncologist [Oncologist] 2023 Nov 02; Vol. 28 (11), pp. 978-985. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Oxford University Press Country of Publication: England NLM ID: 9607837 Publication Model: Print Cited Medium: Internet ISSN: 1549-490X (Electronic) Linking ISSN: 10837159 NLM ISO Abbreviation: Oncologist Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2022- : Oxford : Oxford University Press Original Publication: Dayton, Ohio : AlphaMed Press, c1996- |
| مواضيع طبية MeSH: | Carcinoma, Non-Small-Cell Lung* , Lung Neoplasms*, Humans ; Kelch-Like ECH-Associated Protein 1 ; Platinum ; NF-E2-Related Factor 2 ; Protein Serine-Threonine Kinases |
| مستخلص: | Background: Direct KRASG12C inhibitors are approved for patients with non-small cell lung cancers (NSCLC) in the second-line setting. The standard-of-care for initial treatment remains immune checkpoint inhibitors, commonly in combination with platinum-doublet chemotherapy (chemo-immunotherapy). Outcomes to chemo-immunotherapy in this subgroup have not been well described. Our goal was to define the clinical outcomes to chemo-immunotherapy in patients with NSCLC with KRASG12C mutations. Patients and Methods: Through next-generation sequencing, we identified patients with advanced NSCLC with KRAS mutations treated with chemo-immunotherapy at 2 institutions. The primary objective was to determine outcomes and determinants of response to first-line chemo-immunotherapy among patients with KRASG12C by evaluating objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). We assessed the impact of coalterations in STK11/KEAP1 on outcomes. As an exploratory objective, we compared the outcomes to chemo-immunotherapy in KRASG12C versus non-G12C groups. Results: One hundred and thirty eight patients with KRASG12C treated with first-line chemo-immunotherapy were included. ORR was 41% (95% confidence interval (CI), 32-41), median PFS was 6.8 months (95%CI, 5.5-10), and median OS was 15 months (95%CI, 11-28). In a multivariable model for PFS, older age (P = .042), squamous cell histology (P = .008), poor ECOG performance status (PS) (P < .001), and comutations in KEAP1 and STK11 (KEAP1MUT/STK11MUT) (P = .015) were associated with worse PFS. In a multivariable model for OS, poor ECOG PS (P = .004) and KEAP1MUT/STK11MUT (P = .009) were associated with worse OS. Patients with KRASG12C (N = 138) experienced similar outcomes to chemo-immunotherapy compared to patients with non-KRASG12C (N = 185) for both PFS (P = .2) and OS (P = .053). Conclusions: We define the outcomes to first-line chemo-immunotherapy in patients with KRASG12C, which provides a real-world benchmark for clinical trial design involving patients with KRASG12C mutations. Outcomes are poor in patients with specific molecular coalterations, highlighting the need to develop more effective frontline therapies. (© The Author(s) 2023. Published by Oxford University Press.) |
| التعليقات: | Erratum in: Oncologist. 2024 Jan 5;29(1):e166. (PMID: 38000087) |
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| معلومات مُعتمدة: | R01 CA279264 United States CA NCI NIH HHS; R01 CA230267 United States CA NCI NIH HHS; P30-CA008748 United States NH NIH HHS; P30 CA008748 United States CA NCI NIH HHS; UL1 TR002384 United States TR NCATS NIH HHS; R01 CA230745 United States CA NCI NIH HHS; P01 CA129243 United States CA NCI NIH HHS |
| فهرسة مساهمة: | Keywords: KRASG12C; chemotherapy; combination therapy; immunotherapy; non-small cell lung cancer |
| المشرفين على المادة: | 0 (Kelch-Like ECH-Associated Protein 1) 49DFR088MY (Platinum) 0 (NF-E2-Related Factor 2) EC 2.7.11.1 (Protein Serine-Threonine Kinases) |
| تواريخ الأحداث: | Date Created: 20230817 Date Completed: 20231108 Latest Revision: 20240423 |
| رمز التحديث: | 20240423 |
| مُعرف محوري في PubMed: | PMC10628591 |
| DOI: | 10.1093/oncolo/oyad197 |
| PMID: | 37589215 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1549-490X |
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| DOI: | 10.1093/oncolo/oyad197 |