KEYNOTE-024: Pembrolizumab (pembro) vs platinum-based chemotherapy (chemo) as first-line therapy for advanced NSCLC with a PD-L1 tumor proportion score (TPS) ≥50%

Date

09 Oct 2016

Session

Presidential Symposium 2

Presenters

Martin Reck

Citation

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

Authors

M. Reck1, D. Rodríguez-Abreu2, A.G. Robinson3, R. Hui4, T. Csoszi5, A. Fülöp6, M. Gottfried7, N. Peled8, A. Tafreshi9, S. Cuffe10, M. O'Brien11, S. Rao12, K. Hotta13, M. Leiby14, G.M. Lubiniecki15, Y. Shentu16, R. Rangwala15, J.R. Brahmer17

Author affiliations

  • 1 Thoracic Oncology, Lung Clinic Grosshansdorf, Airway Research Center North (ARCN), member of the German Center for Lung Research (DZL), 22927 - Grosshansdorf/DE
  • 2 Medical Oncology, Hospital Universitario Insular de Gran Canaria, Las Palmas de Gran Canaria/ES
  • 3 Oncology, Cancer Centre of Southeastern Ontario at Kingston General Hospital and Queens University, Kingston/CA
  • 4 Medical Oncology, Westmead Hospital and University of Sydney, Sydney/AU
  • 5 Onkologiai Kozpont, Hetenyi G Korhaz, 5004 - Szolnok/HU
  • 6 Oncology, National Koranyi Institute of Pulmonology, Budapest/HU
  • 7 Oncology, Meir Medical Center, Kfar Saba/IL
  • 8 Thoracic Cancer Unit, Davidoff Cancer Center, Petach Tiqwa/IL
  • 9 Medical Oncology, Southern Medical Day Care Centre, Wollongong/AU
  • 10 Medical Oncology, St James's Hospital, Dublin/IE
  • 11 Medical Oncology, Royal Marsden Hospital NHS Foundation Trust, London/GB
  • 12 Oncology, MedStar Franklin Square Medical Center, Baltimore/US
  • 13 Center For Innovative Clinical Medicine, Okayama University Hospital, Okayama/JP
  • 14 Global Scientific And Medical Publications, Merck & Co., Inc., Kenilworth/US
  • 15 Oncology Clinical Development, Merck & Co., Inc., Kenilworth/US
  • 16 Biostatistics And Research Decision Statistics, Merck & Co., Inc., Kenilworth/US
  • 17 Department Of Oncology, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore/US
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Resources

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Background

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.

Methods

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%.

Results

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 < 0.001; median 10.3 mo vs 6.0 mo). With 108 deaths, pembro also significantly prolonged OS (HR 0.60, 95% CI 0.41-0.89, P = 0.005; 6-mo OS 80% vs 72%). Pembro was also associated with higher ORR (45% vs 28%), longer response duration (median NR vs 6.3 mo), and lower incidence of any-grade (73% vs 90%) and grade 3-5 (27% vs 53%) treatment-related AEs.

Conclusions

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 identification

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 & Co., Inc.

Funding

Merck & Co., Inc.

Disclosure

M. Reck: Served as Advisory board member for Roche, Lilly, BMS, MSD, AstraZeneca, Pfizer, Boehringer-Ingelheim, and Celgene. Also, served on Speakers' bureau for Roche, Lilly, BMS, MSD, AstraZeneca, Pfizer, Boehringer-Ingelheim, and Celgene. D. Rodríguez-Abreu: Advisory board member, speakers' bureau, and travel expenses: BMS, MSD, Boehringer, Roche. A.G. Robinson: Speakers' bureau: Merck, Pfizer, Roche, Novartis. R. Hui: Advisory board member: MSD, AstraZeneca, Pfizer, Novartis. N. Peled: Speakers' bureau and travel expenses: MSD. A. Tafreshi: Advisory board member: Merck, Ipsen. M. O'Brien: Advisory board member: MSD, Bristol-Myers Squibb, Abbive, Boehringer Ingelheim, Pierre Fabre; Travel expenses: Bristol-Myers Squibb. K. Hotta: Speakers' bureau: Chugai, Lilly, AstraZeneca, Daiichi-Sankyo Pharmaceutical, Boehringer-Ingelheim, Nihon Kayaku, Taiho Pharmaceutical, and Sanofi-Aventis; Research funding: Merck, Chgai, Lilly. M. Leiby, G.M. Lubiniecki, Y. Shentu, R. Rangwala: Employment and stock options: Merck & Co., Inc. J.R. Brahmer: Advisory board: Bristol-Myers Squibb, MedImmune/AstraZeneca, Merck; Advisory board: Bristol-Myers Squibb (uncompensated), Celgene, Lilly, MedImmume/AstraZeneca. All other authors have declared no conflicts of interest.

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Presentation

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