First-Line Nivolumab Plus Ipilimumab With Chemotherapy Versus Chemotherapy Alone for Metastatic NSCLC in CheckMate 9LA: 3-Year Clinical Update and Outcomes in Patients With Brain Metastases or Select Somatic Mutations
| Autor: | Luis G. Paz-Ares, Tudor-Eliade Ciuleanu, Manuel Cobo, Jaafar Bennouna, Michael Schenker, Ying Cheng, Oscar Juan-Vidal, Hideaki Mizutani, Alejo Lingua, Felipe Reyes-Cosmelli, Niels Reinmuth, Juliana Menezes, Jacek Jassem, Svetlana Protsenko, Eduardo Richardet, Enriqueta Felip, Kynan Feeney, Bogdan Zurawski, Aurelia Alexandru, Emmanuel de la Mora Jimenez, Shaker Dakhil, Shun Lu, Martin Reck, Thomas John, Nan Hu, Xiaoqing Zhang, Judi Sylvester, Laura J. Eccles, Diederik J. Grootendorst, David Balli, Jaclyn Neely, David P. Carbone |
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| Přispěvatelé: | Institut Català de la Salut, [Paz-Ares LG] Medical Oncology Department, Hospital Universitario 12 de Octubre, Universidad Complutense de Madrid, Madrid, Spain. [Ciuleanu TE] Department of Medical Oncology, Institutul Oncologic Prof Dr Ion Chiricuta and University of Medicine and Pharmacy Iuliu Hatieganu, Cluj-Napoca, Romania. [Cobo M] Department of Medical Oncology, Unidad de Gestión Clínica Intercentros de Oncología Médica, Hospitales Universitarios Regional y Virgen de la Victoria, IBIMA, Málaga, Spain. [Bennouna J] Department of Pneumology, Thoracic Oncology, University Hospital of Nantes and INSERM, CRCINA, Nantes, France. [Schenker M] Department of Medical Oncology, SF Nectarie Oncology Center, Craiova, Romania. [Cheng Y] Department of Oncology, Jilin Cancer Hospital, Changchun, Jilin, People’s Republic of China. [Felip E] Servei d’Oncologia Mèdica, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain, Vall d'Hebron Barcelona Hospital Campus |
| Rok vydání: | 2023 |
| Předmět: |
Pulmonary and Respiratory Medicine
Otros calificadores::/uso terapéutico [Otros calificadores] terapéutica::terapéutica::farmacoterapia::protocolos antineoplásicos::terapéutica::farmacoterapia::protocolos de quimioterapia antineoplásica combinada [TÉCNICAS Y EQUIPOS ANALÍTICOS DIAGNÓSTICOS Y TERAPÉUTICOS] Otros calificadores::Otros calificadores::/farmacoterapia [Otros calificadores] diagnóstico::pronóstico::resultado del tratamiento [TÉCNICAS Y EQUIPOS ANALÍTICOS DIAGNÓSTICOS Y TERAPÉUTICOS] Neoplasms::Neoplasms by Site::Thoracic Neoplasms::Respiratory Tract Neoplasms::Lung Neoplasms::Bronchial Neoplasms::Carcinoma Bronchogenic::Carcinoma Non-Small-Cell Lung [DISEASES] neoplasias::neoplasias por localización::neoplasias torácicas::neoplasias del tracto respiratorio::neoplasias pulmonares::neoplasias de los bronquios::carcinoma broncogénico::carcinoma de pulmón de células no pequeñas [ENFERMEDADES] Other subheadings::Other subheadings::/drug therapy [Other subheadings] Diagnosis::Prognosis::Treatment Outcome [ANALYTICAL DIAGNOSTIC AND THERAPEUTIC TECHNIQUES AND EQUIPMENT] Quimioteràpia combinada Oncology Therapeutics::Therapeutics::Drug Therapy::Antineoplastic Protocols::Therapeutics::Drug Therapy::Antineoplastic Combined Chemotherapy Protocols [ANALYTICAL DIAGNOSTIC AND THERAPEUTIC TECHNIQUES AND EQUIPMENT] Avaluació de resultats (Assistència sanitària) Other subheadings::/therapeutic use [Other subheadings] Pulmons - Càncer - Tractament |
| Zdroj: | Scientia |
| ISSN: | 1556-0864 |
| Popis: | Non–small cell lung cancer; Brain metastases; Somatic mutations Càncer de pulmó de cèl·lules no petites; Metàstasis cerebrals; Mutacions somàtiques Cáncer de pulmón de células no pequeñas; Metástasis cerebrales; Mutaciones somáticas Introduction In the phase 3 CheckMate 9LA study, nivolumab plus ipilimumab with chemotherapy prolonged overall survival (OS) versus chemotherapy alone. We report updated efficacy and safety (≥3 y of follow-up), clinical outcomes in patients with baseline brain metastases, and exploratory somatic mutation analyses. Methods Adults with stage IV or recurrent NSCLC, no known sensitizing EGFR or ALK alterations, and Eastern Cooperative Oncology Group performance status less than or equal to 1 were randomized 1:1 to nivolumab 360 mg every 3 weeks plus ipilimumab 1 mg/kg every 6 weeks with chemotherapy (two cycles) or chemotherapy alone (four cycles). Assessments included OS, progression-free survival (PFS), and objective response rate. Exploratory analyses included systemic and intracranial efficacy in patients with or without baseline brain metastases, in addition to OS and PFS by KRAS, TP53, STK11, and KEAP1 somatic mutation status in patients with nonsquamous NSCLC. Results With a minimum follow-up of 36.1 months, nivolumab plus ipilimumab with chemotherapy continued to prolong OS versus chemotherapy alone in the intent-to-treat population (median [hazard ratio; 95% confidence interval] OS: 15.8 versus 11.0 mo [0.74; 0.62–0.87]; 3-y OS: 27% versus 19%). Efficacy outcomes were improved in patients with pretreated baseline brain metastases (median [hazard ratio; 95% confidence interval] OS: 19.3 versus 6.8 mo [0.45; 0.29–0.70]; systemic PFS: 9.7 versus 4.1 mo [0.44; 0.28–0.69]; intracranial PFS: 11.4 versus 4.6 mo [0.42; 0.26–0.68]). A trend of OS benefit was observed in patients treated with nivolumab plus ipilimumab with chemotherapy versus chemotherapy alone, despite KRAS, TP53, and STK11 tumor mutations. Extended follow-up revealed no new safety signals. Conclusions With a 3-year minimum follow-up, nivolumab plus ipilimumab with two cycles of chemotherapy continued to have long-term, durable efficacy versus chemotherapy alone; a manageable safety profile; and survival benefit in patients with or without baseline brain metastases or select somatic mutations, further supporting the regimen as first-line treatment for patients with metastatic NSCLC. This study was supported by Bristol Myers Squibb (Princeton, NJ). |
| Databáze: | OpenAIRE |
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