LBA43 - Antitumor activity of pembrolizumab (Pembro; MK-3475) and correlation with programmed death ligand 1 (PD-L1) expression in a pooled analysis of pat...

Date 28 September 2014
Event ESMO 2014
Session NSCLC, metastatic 2
Topics Immunotherapy
Non-Small Cell Lung Cancer
Presenter Edward Garon
Citation Annals of Oncology (2014) 25 (5): 1-41. 10.1093/annonc/mdu438
Authors E.B. Garon1, L. Gandhi2, N. Rizvi3, R. Hui4, A.S. Balmanoukian5, A. Patnaik6, J.P. Eder7, G.R. Blumenshein8, C. Aggarwal9, J. Soria10, M. Ahn11, M.A. Gubens12, S.S. Ramalingam13, E. Johnson14, H. Arkenau15, G.M. Lubiniecki16, J. Zhang17, R.Z. Rutledge16, K. Emancipator18, N. Leighl19
  • 1Medicine, David Geffen School of Medicine at UCLA, 90404 - Santa Monica/US
  • 2Medical Oncology, Dana-Farber Cancer Institute, Boston/US
  • 3Department Of Medicine, Memorial Sloan Kettering Cancer Center, New York/US
  • 4Department Of Medical Oncology, Crown Princess Mary Cancer Centre, Westmead Hospital, Sydney/AU
  • 5Oncology, The Angeles Clinic and Research Institute, Santa Monica/US
  • 6Phase I, The START Center for Cancer Care, 78229 - San Antonio/US
  • 7Medical Oncology, Yale University, New Haven/US
  • 8Thoracic/head And Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston/US
  • 9Department Of Medicine, Abramson Cancer Center of the University of Pennsylvania, Philadelphia/US
  • 10Medicine, Gustave Roussy Cancer Campus, 94805 - Villejuif/FR
  • 11Section Of Hematology-oncology, Department Of Medicine, Samsung Medical Center, Seoul/KR
  • 12Division Of Hematology & Oncology, Department Of Medicine, University of California, San Francisco, San Francisco/US
  • 13Department Of Hematology And Medical Oncology, Winship Cancer Institute of Emory University, Atlanta/US
  • 14Oncology, Mayo Clinic Florida, Jacksonville/US
  • 15Oncology, Sarah Cannon Research Institute, London/GB
  • 16Clinical Research, Merck & Co., Inc., Whitehouse Station/US
  • 17Bards, Merck & Co., Inc., North Wales/US
  • 18Molecular Biomarkers And Diagnostics, Merck Research Laboratories, Rahway/US
  • 19Medical Oncology, Princess Margaret Cancer Centre, Toronto/CA



The anti-PD-1 antibody pembro has shown durable antitumor activity and acceptable toxicity in treatment-naive and previously treated advanced NSCLC. Correlation between tumor PD-L1 expression and improved pembro antitumor activity has been observed.


282 pts with treatment-naive or previously treated advanced NSCLC enrolled in randomized and nonrandomized cohorts of the phase 1 KEYNOTE-001 study were analyzed. To inform enrollment, tumor PD-L1 expression was determined prospectively by a prototype IHC assay (PA) in all pts. Samples were independently reanalyzed using a clinical trial IHC assay (CTA). Pembro was given at 2 mg/kg every 3 weeks (Q3W), 10 mg/kg Q3W, or 10 mg/kg Q2W until progression, death, or unacceptable toxicity. Overall response rate (ORR) was assessed per RECIST v1.1 by central review and per immune-related response criteria (irRC) by investigator review.


Mature data are available for 262 pts (5.4-mo median follow-up). Grade 3–5 drug-related AEs occurred in 24 (9%) pts, most commonly pneumonitis (n = 5 [n = 3 grade 3, n = 2 grade 4]). ORR (RECIST/irRC) in pts with measurable disease at baseline was 21%/23% overall (26%/47% treatment naive, 20%/18% previously treated) and was similar in pts with squamous (18%/25%) and nonsquamous (23%/23%) histology. ORR was 33%/67% at 2 mg/kg Q3W (n = 6), 21%/22% at 10 mg/kg Q3W (n = 141), and 21%/22% at 10 mg/kg Q2W (n = 115). As assessed by the PA, ORR was 23%/25% in pts with ≥1% PD-L1 staining and 9%/13% in pts with no PD-L1 staining. Preliminary median PFS will be presented, as will data for an additional 20 previously treated pts who received pembro 2 mg/kg Q3W. To date, data for PD-L1 staining using the CTA are available for nearly one-half of pts. In these pts, ORR (RECIST/irRC) was 39%/47% in pts with strong PD-L1 expression (≥50% staining) and 16%/9% in pts with weak/negative PD-L1 expression.


Pembro is tolerable and provides antitumor activity in treatment-naive or previously treated advanced NSCLC, regardless of dose/schedule. Pts with strong PD-L1 tumor expression may derive particular benefit from pembro.


E.B. Garon: Corporate-sponsored research: Merck, Pfizer, Genentech, AstraZeneca, Novartis, Puma; L. Gandhi: Serves on advisory boards for Genentech/Roche and has received consulting fees from Merck; N. Rizvi: Has served on advisory boards for Bristol-Myers Squibb, Merck, Roche, and AstraZeneca; R. Hui: Has served on advisory boards for Merck; A. Patnaik: Has received research grants from Merck; J-C. Soria: Has served as consultant to Merck; M.A. Gubens: Has served as advisory board member, without compensation, for Celgene and Roche/Genentech, and has received research grants from Merck, Celgene, and MedImmune; S.S. Ramalingam: Has served on advisory boards for Genentech and AstraZeneca; G.M. Lubiniecki, J. Zhang and K. Emancipator: Is an employee of Merck & Co., Inc.; R.Z. Rutledge: Is an employee of and holds stock in Merck & Co., Inc. All other authors have declared no conflicts of interest.