437O - KEYNOTE-024: Pembrolizumab (pembro) vs platinum-based chemotherapy (chemo) as first-line therapy for advanced NSCLC with a PD-L1 tumor proportion s...

Date 18 December 2016
Event ESMO Asia 2016 Congress
Session Presidential Symposium
Topics Anticancer Agents
Non-Small-Cell Lung Cancer, Metastatic
Presenter Martin Reck
Citation Annals of Oncology (2016) 27 (suppl_9): ix139-ix156. 10.1093/annonc/mdw594
Authors M. Reck1, D. Rodríguez-Abreu2, A. Robinson3, R. Hui4, T. Csoszi5, A. Fülöp6, M. Gottfried7, N. Peled8, A. Tafreshi9, S. Cuffe10, M.E. O'Brien11, S. Rao12, K. Hotta13, M. Leiby14, G. Lubiniecki15, Y. Shentu16, R. Rangwala15, J. Brahmer17
  • 1Thoracic Oncology, Lung Clinic Grosshansdorf, Airway Research Center North (ARCN), member of the German Center for Lung Research (DZL), 22927 - Grosshansdorf/DE
  • 2Medical Oncology, Hospital Universitario Insular de Gran Canaria, 35016 - Las Palmas/ES
  • 3Oncology, Cancer Centre of Southeastern Ontario at Kingston General Hospital, K7L 5P9 - Kingston/CA
  • 4Medical Oncology, The Crown Princess Mary Cancer Centre, 2145 - Westmead/AU
  • 5Hetenyi G Korhaz Onkologiai Kozpont, Hetenyi Geza Korhaz, Onkologiai Kozpont, 5004 - Szolnok/HU
  • 6Oncology, National Koranyi Institute of Pulmonology, H-1121 - Budapest/HU
  • 7Department Of Oncology, Meir Medical Center, 4428164 - Kfar Saba/IL
  • 8Thoracic Cancer Unit, Davidoff Cancer Center, Tel Aviv University, 49100 - Petach Tikva/IL
  • 9Medical Oncology, Southern Medical Day Care Centre, 2500 - Wollongong/AU
  • 10Medical Oncology, St James's Hospital, 8 - Dublin/IE
  • 11Medical Oncology, Royal Marsden Hospital NHS Foundation Trust, SW3 6JJ - London/GB
  • 12Oncology, MedStar Franklin Square Medical Center, 21237 - Baltimore/US
  • 13Center For Innovative Clinical Medicine, Okayama University Hospital, 700-0082 - Okayama/JP
  • 14Global Scientific And Medical Publications, Merck & Co., Inc., 07033 - Kenilworth/US
  • 15Oncology Clinical Development, Merck & Co., Inc., 07033 - Kenilworth/US
  • 16Biostatistics And Research Design Sciences, Merck & Co., Inc., 07033 - Kenilworth/US
  • 17Department Of Oncology, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, 21231 - Baltimore/US



Platinum-based doublet chemo is the standard first-line therapy for advanced NSCLC without a treatable oncogenic aberration. Pembro (anti–PD-1) is approved in the US and EU for previously treated, PD-L1–expressing advanced NSCLC. KEYNOTE-024 (NCT02142738) is an open-label, phase 3 study of pembro vs platinum-doublet chemo as first-line therapy for advanced NSCLC of PD-L1 TPS ≥50% without treatable EGFR mutations or ALK translocations.


Patients (pts) were randomized to 35 cycles of pembro 200 mg Q3W or 4-6 cycles of investigator’s choice of carboplatin or cisplatin + pemetrexed, carboplatin or cisplatin + gemcitabine, or carboplatin + paclitaxel, with optional pemetrexed maintenance for nonsquamous NSCLC. Pts in the chemo arm could crossover to pembro upon PD. Response was assessed every 9 wk (RECIST v1.1, central imaging vendor). Primary end point was PFS. Secondary end points were OS, ORR, and safety. Differences in PFS and OS were assessed in the ITT population using the stratified log-rank test. At the prespecified second interim analysis (data cutoff, May 9, 2016), the study had 97% power to detect a HR of 0.55 for PFS at a 1-sided α = 2.0%.


From Sep 19, 2014, to Oct 29, 2015, 305 pts from 16 countries were randomized: 154 to pembro, 151 to chemo. After a median follow-up of 11.2 mo, 48% of pts remained on pembro, 10% remained on chemo, and 44% crossed over from chemo to pembro upon PD. With 189 events, pembro significantly prolonged PFS over chemo (HR 0.50, 95% CI 0.37-0.68, P 


Pembro demonstrated superior PFS and OS over platinum-based chemo in pts with advanced NSCLC of PD-L1 TPS ≥50%. Along with the lower rate of treatment-related AEs, these data suggest pembro may be the new standard of care for first-line therapy of PD-L1–expressing advanced NSCLC without treatable oncogenic aberrations.

Clinical trial indentification

ClinicalTrials.gov number NCT02142738, originally posted May 16, 2014; EudraCT number 2014-000323-25, originally issued 27-Mar-2014

Legal entity responsible for the study

Merck Sharp & Dohme, Corp., a subsidiary of Merck & Co., Inc.


Merck Sharp & Dohme, Corp., a subsidiary of Merck & Co., Inc.


M. Reck: Advisory board member and speakers\' bureau: Roche, Lilly, Bristol-Myers Squibb, MSD, AstraZeneca, Pfizer, Boehringer-Ingelheim, Celgene. D. Rodríguez-Abreu: Advisory Board, Speakers\' Bureau, and Travel Expenses: BMS, MSD, Boehringer, Roche. A. Robinson: Speakers\' Bureau: Merck, Pfizer, Roche, Novartis. R. Hui: Advisory Board: MSD, AstraZeneca, Pfizer, Novartis. N. Peled: Speakers\' Bureau and Travel Expenses: MSD. A. Tafreshi: Advisory Board: Merck, Ipsen. M.E. O\'Brien: Advisory Board: MSD, BMS, Abbvie, Boehringer-Ingelheim, Pierre Fabre Travel expenses: BMS. K. Hotta: Speakers\' Bureau: Chugai, Lilly, AstraZeneca, Daiichi-Sankyo Pharmaceutical, Boehringer-Ingelheim, Nihon Kayaku, Taiho Pharmaceutical, Sanofi-Aventis Research Funding: Merck, Chugai Pharmaceutical, Eli Lilly Japan. M. Leiby, G. Lubiniecki, Y. Shentu, R. Rangwala: Employment and stock options: Merck & Co., Inc. J. Brahmer: Advisory Board/consultant: BMS, Celgene, Lilly, Merck Research Funding: BMS, Merck, MedImmune/AstraZeneca. All other authors have declared no conflicts of interest.