Hossein Borghaei1, Corey J Langer2, Shirish Gadgeel3, Vassiliki A Papadimitrakopoulou4, Amita Patnaik5, Steven F Powell6, Ryan D Gentzler7, Renato G Martins8, James P Stevenson9, Shadia I Jalal10, Amit Panwalkar11, James Chih-Hsin Yang12, Matthew Gubens13, Lecia V Sequist14, Mark M Awad15, Joseph Fiore16, Sanatan Saraf16, Steven M Keller16, Leena Gandhi17. 1. Hematology and Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania. Electronic address: Hossein.borghaei@fccc.edu. 2. Department of Medicine, Abramson Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania. 3. Thoracic Oncology, Karmanos Cancer Institute/Wayne State University, Detroit, Michigan. 4. Thoracic/Head and Neck Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas. 5. Clinical Research, START Center for Cancer Care, San Antonio, Texas. 6. Oncology, Sanford Health, Sioux Falls, South Dakota. 7. Hematology/Oncology, University of Virginia, Charlottesville, Virginia. 8. Medicine, University of Washington, Seattle, Washington. 9. Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio. 10. Internal Medicine, Indiana University School of Medicine, Indianapolis, Indiana. 11. Hematology/Oncology, Sanford Roger Maris Cancer Center, Fargo, North Dakota. 12. Department of Oncology, National Taiwan University Hospital, Taipei, Republic of China. 13. Medical Oncology, University of California San Francisco, San Francisco, California. 14. Hematology/Oncology, Massachusetts General Hospital, Boston, Massachusetts. 15. Thoracic Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts. 16. Oncology Clinical Development, Merck & Co., Inc., Kenilworth, New Jersey. 17. Laura and Isaac Perlmutter Cancer Center, New York University Langone Medical Center, New York, New York.
Abstract
INTRODUCTION: Cohort G of KEYNOTE-021 (NCT02039674) evaluated the efficacy and safety of pembrolizumab plus pemetrexed-carboplatin (PC) versus PC alone as first-line therapy for advanced nonsquamous NSCLC. At the primary analysis (median follow-up time 10.6 months), pembrolizumab significantly improved objective response rate (ORR) and progression-free survival (PFS); the hazard ratio (HR) for overall survival (OS) was 0.90 (95% confidence interval [CI]: 0.42‒1.91). Herein, we present an updated analysis. METHODS: A total of 123 patients with previously untreated stage IIIB/IV nonsquamous NSCLC without EGFR and/or ALK receptor tyrosine kinase gene (ALK) aberrations were randomized 1:1 to four cycles of PC with or without pembrolizumab, 200 mg every 3 weeks. Pembrolizumab treatment continued for 2 years; maintenance pemetrexed was permitted in both groups. Eligible patients in the PC-alone group with radiologic progression could cross over to pembrolizumab monotherapy. p Values are nominal (one-sided p < 0.025). RESULTS: As of December 1, 2017, the median follow-up time was 23.9 months. The ORR was 56.7% with pembrolizumab plus PC versus 30.2% with PC alone (estimated difference 26.4% [95% CI: 8.9%‒42.4%, p = 0.0016]). PFS was significantly improved with pembrolizumab plus PC versus PC alone (HR = 0.53, 95% CI: 0.33‒0.86, p = 0.0049). A total of 41 patients in thePC-alone group received subsequent anti‒programmed death 1/anti‒programmed death ligand 1 therapy. The HR for OS was 0.56 (95% CI: 0.32‒0.95, p = 0.0151). Forty-one percent of patients in the pembrolizumab plus PC group and 27% in the PC-alone group had grade 3 to 5 treatment-related adverse events. CONCLUSIONS: The significant improvements in PFS and ORR with pembrolizumab plus PC versus PC alone observed in the primary analysis were maintained, and the HR for OS with a 24-month median follow-up was 0.56, favoring pembrolizumab plus PC.
RCT Entities:
INTRODUCTION: Cohort G of KEYNOTE-021 (NCT02039674) evaluated the efficacy and safety of pembrolizumab plus pemetrexed-carboplatin (PC) versus PC alone as first-line therapy for advanced nonsquamous NSCLC. At the primary analysis (median follow-up time 10.6 months), pembrolizumab significantly improved objective response rate (ORR) and progression-free survival (PFS); the hazard ratio (HR) for overall survival (OS) was 0.90 (95% confidence interval [CI]: 0.42‒1.91). Herein, we present an updated analysis. METHODS: A total of 123 patients with previously untreated stage IIIB/IV nonsquamous NSCLC without EGFR and/or ALK receptor tyrosine kinase gene (ALK) aberrations were randomized 1:1 to four cycles of PC with or without pembrolizumab, 200 mg every 3 weeks. Pembrolizumab treatment continued for 2 years; maintenance pemetrexed was permitted in both groups. Eligible patients in the PC-alone group with radiologic progression could cross over to pembrolizumab monotherapy. p Values are nominal (one-sided p < 0.025). RESULTS: As of December 1, 2017, the median follow-up time was 23.9 months. The ORR was 56.7% with pembrolizumab plus PC versus 30.2% with PC alone (estimated difference 26.4% [95% CI: 8.9%‒42.4%, p = 0.0016]). PFS was significantly improved with pembrolizumab plus PC versus PC alone (HR = 0.53, 95% CI: 0.33‒0.86, p = 0.0049). A total of 41 patients in the PC-alone group received subsequent anti‒programmed death 1/anti‒programmed death ligand 1 therapy. The HR for OS was 0.56 (95% CI: 0.32‒0.95, p = 0.0151). Forty-one percent of patients in the pembrolizumab plus PC group and 27% in the PC-alone group had grade 3 to 5 treatment-related adverse events. CONCLUSIONS: The significant improvements in PFS and ORR with pembrolizumab plus PC versus PC alone observed in the primary analysis were maintained, and the HR for OS with a 24-month median follow-up was 0.56, favoring pembrolizumab plus PC.
Authors: Diego de Miguel-Perez; Alessandro Russo; Oscar Arrieta; Murat Ak; Feliciano Barron; Muthukumar Gunasekaran; Priyadarshini Mamindla; Luis Lara-Mejia; Christine B Peterson; Mehmet E Er; Vishal Peddagangireddy; Francesco Buemi; Brandon Cooper; Paolo Manca; Rena G Lapidus; Ru-Ching Hsia; Andres F Cardona; Aung Naing; Sunjay Kaushal; Fred R Hirsch; Philip C Mack; Maria Jose Serrano; Vincenzo Adamo; Rivka R Colen; Christian Rolfo Journal: J Exp Clin Cancer Res Date: 2022-06-02
Authors: Martin Reck; Delvys Rodríguez-Abreu; Andrew G Robinson; Rina Hui; Tibor Csőszi; Andrea Fülöp; Maya Gottfried; Nir Peled; Ali Tafreshi; Sinead Cuffe; Mary O'Brien; Suman Rao; Katsuyuki Hotta; Ticiana A Leal; Jonathan W Riess; Erin Jensen; Bin Zhao; M Catherine Pietanza; Julie R Brahmer Journal: J Clin Oncol Date: 2021-04-19 Impact factor: 50.717