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Randomized, phase 2 study of carboplatin and pemetrexed with or without pembrolizumab as first-line therapy for advanced NSCLC: KEYNOTE-021 cohort G

Date

09 Oct 2016

Session

Presidential Symposium 2

Presenters

Corey Langer

Citation

Annals of Oncology (2016) 27 (6): 1-36. 10.1093/annonc/mdw435

Authors

C. Langer1, S.M. Gaddgeel2, H. Borghaei3, V.A. Papadimitrakopoulou4, A. Patnaik5, S. Powell6, R.D. Gentzler7, R.G. Martins8, J.P. Stevenson9, S.I. Jalal10, A. Panwalkar11, J.C. Yang12, M.A. Gubens13, L.V. Sequist14, M.M. Awad15, J.J. Fiore16, Y. Ge16, H. Raftopoulos16, L. Gandhi17

Author affiliations

  • 1 Oncology, Abramson Cancer Center, University of Pennsylvania, 19104 - Philadelphia/US
  • 2 Clinical Hematology/oncology, Karmanos Cancer Institute and Wayne State University, Detroit/US
  • 3 Department Of Hematology/oncology, Fox Chase Cancer Center, Philadelphia/US
  • 4 Thoracic/head And Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston/US
  • 5 Department Of Clinical Research, South Texas Accelerated Research Therapeutics (START), San Antonio/US
  • 6 Oncology, Sanford Health, Sioux Falls/US
  • 7 Hematology/oncology, University of Virginia, Charlottesville/US
  • 8 Medicine, Division Of Medical Oncology, University of Washington Seattle Cancer Care Alliance, Seattle/US
  • 9 Hematology And Oncology, Cleveland Clinic, Cleveland/US
  • 10 Internal Medicine, Indiana University School of Medicine, Indianapolis/US
  • 11 Medical Oncology, Sanford Roger Maris Cancer Center, Fargo/US
  • 12 Oncology, National Taiwan University Hospital, Taipei/TW
  • 13 Department Of Medicine, University of California San Francisco, San Francisco/US
  • 14 Center For Thoracic Cancers, Massachusetts General Hospital, 02114 - Boston/US
  • 15 Thoracic Oncology, Dana-Farber Cancer Institute, Boston/US
  • 16 Clinical Sciences & Study Management, Merck & Co., Inc., Kenilworth/US
  • 17 Medical Oncology, Dana-Farber Cancer Institute, Boston/US
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Resources

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Background

Pembrolizumab (pembro) monotherapy exhibits robust antitumor activity in PD-L1─expressing advanced NSCLC. Cohort G of the multicenter, open-label, phase 1/2 KEYNOTE-021 study (NCT02039674) evaluated the efficacy and safety of pembro + carboplatin and pemetrexed (CP) vs CP alone as first-line therapy for advanced nonsquamous NSCLC.

Methods

Key eligibility criteria were stage IIIB/IV, chemotherapy-naive, nonsquamous NSCLC, ECOG PS 0-1, and no EGFR mutation or ALK translocation. Patients (pts) were randomized to 4 cycles of carboplatin AUC 5 + pemetrexed 500 mg/m2 Q3W ± 24 mo of pembro 200 mg Q3W; maintenance pemetrexed was allowed in both arms. Randomization was stratified by PD-L1 tumor proportion score ≥1% vs <1%. Eligible pts with radiologic progression on CP could crossover to pembro monotherapy. Primary end point was ORR, with PFS as the key secondary end point; both were assessed per RECIST v1.1 by blinded independent central review. ORR and PFS superiority thresholds were one-sided α = 0.025.

Results

123 pts were enrolled: 60 in the pembro + CP arm, 63 in the CP arm. Demographics were generally balanced between treatment arms. As of Aug 8, 2016, median follow-up was 10.6 mo (range, 0.8-19.3); median exposure was 8.0 mo for pembro + CP and 4.9 mo for CP. In the CP arm, 43 pts discontinued therapy; 32 received subsequent anti–PD-1 therapy as part of crossover (n = 20) or off study (n = 12). Pembro + CP significantly improved ORR (55% vs 29%; P = 0.0016) and PFS (HR 0.53, 95% CI 0.31-0.91, P = 0.0102; median 13.0 vs 8.9 mo). Overall survival was similar; 6-mo survival rates were 92% in each arm. Without adjusting for exposure, for pembro + CP vs CP, treatment-related AEs led to discontinuation in10% vs 13%, were of grade ≥3 severity in 39% vs 26%, and led to death in 2% (sepsis, n = 1) vs 3% (sepsis and pancytopenia, n = 1 each). The most common any-grade treatment-related AEs were fatigue (64% vs 40%), nausea (58% vs 44%), and anemia (32% vs 53%).

Conclusions

Pembro 200 mg Q3W + CP demonstrated a statistically significant, clinically relevant ORR and PFS benefit over CP alone and had a manageable, safety profile as first-line therapy in patients with advanced nonsquamous NSCLC.

Clinical trial identification

ClinicalTrials.gov, number NCT02039674; first posted January 16, 2014

Legal entity responsible for the study

Merck & Co., Inc.

Funding

Merck & Co., Inc.

Disclosure

S.M. Gaddgeel: Research funding: Roche, Janssen, AstraZeneca, Merck, Pfizer, Millenium, Clovis, Novartis, Halozyme, Acerta Consultant/advisory role: Novartis, Roche, Pfizer, Boehringer-Ingelheim, Ariad. H. Borghaei: Advisory board: BMS, Lilly, Genentech, Pfizer, Boehringer-Ingelheim, Troyogene, Celgene Research funding for clinical trials: Millennium/Takeda, Merck, Celgene Travel expenses: BMS, Lilly, Genentech, Celgene. V.A. Papadimitrakopoulou: Advisory board member and research funding: Merck. A. Patnaik, S. Powell: Research funding: Merck. R.D. Gentzler: Advisory board: Clovis Oncology, Ariad Research funding: Merck, Bristol-Myers Squibb J.P. Stevenson: Research funding: Merck, Bayer. J.C-H. Yang: Advisory board: Boehringer-Ingelheim, Eli Lilly, Bayer, Roche/Genentech/Chugai, Astellas, MSD, Merck Serono, Pfizer, Novartis, Clovis, Celgene, Merrimack, Yuhan Pharmaceuticals, BMS, Ono Pharmaceutical, AstraZeneca. M.A. Gubens: Advisory board: Ariad, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Calithera, Clovis, Genentech/Roche, Nektar, Pfizer Research funding: Celgene, Genentech/Roche, Merck, Novartis, OncoMed. L.V. Sequist: Uncompensated consultant: Clovis, Boehringer Ingelheim, Merrimack, Novartis, Taiho Compensated consultant: AstraZeneca, Ariad, Genentech. M.M. Awad: Advisory board: Genentech, Merck, Pfizer, Boehringer Ingelheim, AbbVie, AstraZeneca J.J. Fiore: Employment: Merck & Co., Inc. Y. Ge, H. Raftopoulos: Employment and stock options: Merck & Co., Inc. L. Gandhi: Advisory Board: AbbVie, Genentech/Roche, Merck, AstraZeneca, Pfizer Research Funding: BMS IION Foundation. All other authors have declared no conflicts of interest.

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