Mark M Awad1, Shirish M Gadgeel2, Hossein Borghaei3, Amita Patnaik4, James Chih-Hsin Yang5, Steven F Powell6, Ryan D Gentzler7, Renato G Martins8, James P Stevenson9, Mehmet Altan10, Shadia I Jalal11, Amit Panwalkar12, Matthew Gubens13, Lecia V Sequist14, Sanatan Saraf15, Bin Zhao15, Bilal Piperdi15, Corey J Langer16. 1. Medical Oncology, Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts. Electronic address: mark_awad@dfci.harvard.edu. 2. Thoracic Oncology, Karmanos Cancer Institute, Wayne State University, Detroit, Michigan. 3. Hematology and Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania. 4. Clinical Research, START Center for Cancer Care, San Antonio, Texas. 5. Department of Oncology, National Taiwan University Hospital and National Taiwan University Cancer Center, Taipei, Republic of China. 6. Oncology, Sanford Health, Sioux Falls, South Dakota. 7. Hematology/Oncology, University of Virginia Cancer Center, Charlottesville, Virginia. 8. Department of Medicine, University of Washington, Seattle, Washington. 9. Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio. 10. Thoracic/Head and Neck Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas. 11. Indiana University School of Medicine, Indianapolis, Indiana. 12. Hematology/Oncology, Sanford Roger Maris Cancer Center, Fargo, North Dakota. 13. Medical Oncology, University of California San Francisco, San Francisco, California. 14. Hematology/Oncology, Massachusetts General Hospital, Boston, Massachusetts. 15. Merck & Co., Inc., Kenilworth, New Jersey. 16. Department of Medicine, Abramson Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania.
Abstract
INTRODUCTION: In cohort G of KEYNOTE-021 (NCT02039674), first-line pembrolizumab plus pemetrexed-carboplatin significantly improved the objective response rate and progression-free survival versus chemotherapy alone with manageable toxicity in advanced nonsquamous NSCLC. We report the long-term outcomes from this study. METHODS:Patients with previously untreated advanced nonsquamous NSCLC without sensitizing EGFR or ALK alterations were randomly assigned 1:1 to receive open-labelpemetrexed 500 mg/m2 plus carboplatin at area under the concentration-time curve of 5 mg/mL/min (four cycles) with or without pembrolizumab 200 mg (up to 2 years), with optional pemetrexed maintenance, each administered every 3 weeks. Eligible patients could crossover from the chemotherapy arm to pembrolizumab monotherapy after progression. Responses were assessed per the Response Evaluation Criteria in Solid Tumors version 1.1. RESULTS: After the median time of 49.4 months from randomization to data cutoff, objective response rate (58% versus 33%) and progression-free survival (median: 24.5 versus 9.9 mo; hazard ratio: 0.54; 95% confidence interval: 0.35‒0.83) remained improved with pembrolizumab combination (n = 60) versus chemotherapy (n = 63), regardless of programmed death ligand 1 status. Median overall survival was 34.5 versus 21.1 months (hazard ratio: 0.71; 95% confidence interval: 0.45‒1.12), despite a 70% crossover rate from chemotherapy alone to anti‒programmed death (ligand) 1 therapy. Among the 12 patients who completed 2 years of pembrolizumab, 92% were alive at data cutoff; the estimated 3-year duration of response rate was 100%. Grade 3 to 5 treatment-related adverse events occurred in 39% of patients receiving pembrolizumab combination and 31% receiving chemotherapy. CONCLUSIONS: First-line pembrolizumab plus pemetrexed-carboplatin continued to show improved response and survival versus chemotherapy alone in advanced nonsquamous NSCLC, with durable clinical benefit in patients who completed 2 years of therapy. No new safety signals were observed with longer follow-up.
RCT Entities:
INTRODUCTION: In cohort G of KEYNOTE-021 (NCT02039674), first-line pembrolizumab plus pemetrexed-carboplatin significantly improved the objective response rate and progression-free survival versus chemotherapy alone with manageable toxicity in advanced nonsquamous NSCLC. We report the long-term outcomes from this study. METHODS:Patients with previously untreated advanced nonsquamous NSCLC without sensitizing EGFR or ALK alterations were randomly assigned 1:1 to receive open-label pemetrexed 500 mg/m2 plus carboplatin at area under the concentration-time curve of 5 mg/mL/min (four cycles) with or without pembrolizumab 200 mg (up to 2 years), with optional pemetrexed maintenance, each administered every 3 weeks. Eligible patients could crossover from the chemotherapy arm to pembrolizumab monotherapy after progression. Responses were assessed per the Response Evaluation Criteria in Solid Tumors version 1.1. RESULTS: After the median time of 49.4 months from randomization to data cutoff, objective response rate (58% versus 33%) and progression-free survival (median: 24.5 versus 9.9 mo; hazard ratio: 0.54; 95% confidence interval: 0.35‒0.83) remained improved with pembrolizumab combination (n = 60) versus chemotherapy (n = 63), regardless of programmed death ligand 1 status. Median overall survival was 34.5 versus 21.1 months (hazard ratio: 0.71; 95% confidence interval: 0.45‒1.12), despite a 70% crossover rate from chemotherapy alone to anti‒programmed death (ligand) 1 therapy. Among the 12 patients who completed 2 years of pembrolizumab, 92% were alive at data cutoff; the estimated 3-year duration of response rate was 100%. Grade 3 to 5 treatment-related adverse events occurred in 39% of patients receiving pembrolizumab combination and 31% receiving chemotherapy. CONCLUSIONS: First-line pembrolizumab plus pemetrexed-carboplatin continued to show improved response and survival versus chemotherapy alone in advanced nonsquamous NSCLC, with durable clinical benefit in patients who completed 2 years of therapy. No new safety signals were observed with longer follow-up.
Authors: M A Siciliano; G Caridà; D Ciliberto; M d'Apolito; C Pelaia; D Caracciolo; C Riillo; P Correale; A Galvano; A Russo; V Barbieri; P Tassone; P Tagliaferri Journal: ESMO Open Date: 2022-04-12
Authors: Andrew F Nyein; Shahla Bari; Stephanie Hogue; Yayi Zhao; Bradley Maller; Sybil Sha; Maria F Gomez; Dana E Rollison; Lary A Robinson Journal: BMC Cancer Date: 2022-01-24 Impact factor: 4.430