Five Year Survival Update From KEYNOTE-010: Pembrolizumab Versus Docetaxel for Previously Treated, Programmed Death-Ligand 1-Positive Advanced NSCLC


Por: Herbst, RS, Garon, EB, Kim, DW, Cho, BC, Gervais, R, Perez-Gracia, JL, Han, JY, Majem, M, Forster, MD, Monnet, I, Novello, S, Gubens, MA, Boyer, M, Su, WC, Samkari, A, Jensen, EH, Kobie, J, Piperdi, B, Baas, P

Publicada: 1 oct 2021 Ahead of Print: 1 sep 2021
Resumen:
Introduction: In the KEYNOTE-010 study, pembrolizumab improved overall survival (OS) versus docetaxel in patients with previously treated, advanced NSCLC with programmed death-ligand 1 (PD-L1) tumor proportion score (TPS) >= 50% and >= 1%. We report 5-year efficacy and safety follow-up for the KEYNOTE-010 study. Methods: Patients were randomized to pembrolizumab 2 mg/kg or 10 mg/kg once every 3 weeks or docetaxel 75 mg/m(2) once every 3 weeks for up to 35 cycles (2 y). Patients who completed pembrolizumab treatment and subsequently had recurrence could receive second-course pembrolizumab for up to 17 cycles (1 y). Pembrolizumab doses were pooled in this analysis. Results: A total of 1034 patients were randomized (pembrolizumab, n = 691; docetaxel, n = 343). Median study follow-up was 67.4 months (range: 60.0-77.9). The hazard ratio (95% confidence interval) for OS was 0.55 (0.44. 0.69) for patients with PD-L1 TPS >= 50% and 0.70 (0.61. 0.80) with PD-L1 TPS >= 1%. The 5-year OS rates for pembrolizumab versus docetaxel were 25.0% versus 8.2% in patients with PD-L1 TPS >= 50% and 15.6% versus 6.5% with PD-L1 TPS >= 1%. Among 79 patients who completed 35 cycles/2 years of pembrolizumab, the OS rate 3 years after completion (similar to 5 y from randomization) was 83.0%. A total of 21 patients received second-course pembrolizumab; 11 (52.4%) had an objective response after starting the second course and 15 (71.4%) were alive at data cutoff. Exploratory biomarker analysis revealed that higher tissue tumor mutational burden (>= 175 mutations per exome) was associated with improved outcomes with pembrolizumab. Conclusions: Pembrolizumab continued to provide long-term benefit than docetaxel in patients with previously treated advanced NSCLC with PD-L1 TPS >= 50% and >= 1%. Our findings confirm pembrolizumab as a standard-of-care treatment in the second-line or later setting. (C) 2021 Published by Elsevier Inc. on behalf of International Association for the Study of Lung Cancer.

Filiaciones:
Herbst, RS:
 Yale Univ, Sch Med, Yale Comprehens Canc Ctr, Sect Med Oncol, 333 Cedar St, New Haven, CT USA

Garon, EB:
 Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA USA

Kim, DW:
 Seoul Natl Univ, Coll Med, Seoul Natl Univ Hosp, Seoul, South Korea

Cho, BC:
 Yonsei Univ, Yonsei Canc Ctr, Coll Med, Seoul, South Korea

Gervais, R:
 Ctr Francois Baclesse, Caen, France

Perez-Gracia, JL:
 Clin Univ Navarra, Pamplona, Spain

Han, JY:
 Natl Canc Ctr, Ctr Lung Canc, Goyang, South Korea

Majem, M:
 Hosp Santa Creu & Sant Pau, Barcelona, Spain

Forster, MD:
 Univ Coll London Hosp, UCL Canc Inst, London, England

Monnet, I:
 Ctr Hosp Intercommunal Creteil, Creteil, France

Novello, S:
 Univ Turin, Azienda Ospedaliero Univ San Luigi, Dept Oncol, Turin, Italy

Gubens, MA:
 Univ Calif San Francisco, San Francisco, CA 94143 USA

Boyer, M:
 Chris Obrien Lifehouse, Camperdown, NSW, Australia

Su, WC:
 Natl Cheng Kung Univ Hosp, Tainan, Taiwan

Samkari, A:
 Merck & Co Inc, Kenilworth, NJ USA

Jensen, EH:
 Merck & Co Inc, Kenilworth, NJ USA

Kobie, J:
 Merck & Co Inc, Kenilworth, NJ USA

Piperdi, B:
 Merck & Co Inc, Kenilworth, NJ USA

Baas, P:
 Netherlands Canc Inst, Amsterdam, Netherlands
ISSN: 15517411
Editorial
ELSEVIER SCIENCE INC, STE 800, 230 PARK AVE, NEW YORK, NY 10169 USA, Estados Unidos America
Tipo de documento: Article
Volumen: 16 Número: 10
Páginas: 1718-1732
WOS Id: 000701853900013
ID de PubMed: 34048946
imagen Bronze

MÉTRICAS