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Showing content from https://pubmed.ncbi.nlm.nih.gov/26712084/ below:

Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial

Randomized Controlled Trial

. 2016 Apr 9;387(10027):1540-1550. doi: 10.1016/S0140-6736(15)01281-7. Epub 2015 Dec 19. Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial Paul Baas², Dong-Wan Kim³, Enriqueta Felip⁴, José L Pérez-Gracia⁵, Ji-Youn Han⁶, Julian Molina⁷, Joo-Hang Kim⁸, Catherine Dubos Arvis⁹, Myung-Ju Ahn¹⁰, Margarita Majem¹¹, Mary J Fidler¹², Gilberto de Castro Jr¹³, Marcelo Garrido¹⁴, Gregory M Lubiniecki¹⁵, Yue Shentu¹⁵, Ellie Im¹⁵, Marisa Dolled-Filhart¹⁵, Edward B Garon¹⁶

Affiliations

¹ Yale School of Medicine, Yale Cancer Center, and Smilow Cancer Hospital, New Haven, CT, USA. Electronic address: roy.herbst@yale.edu.
² The Netherlands Cancer Institute and The Academic Medical Hospital Amsterdam, Amsterdam, Netherlands.
³ Seoul National University Hospital, Seoul, South Korea.
⁴ Vall D'Hebron University Hospital and Vall d'Hebron Institute of Oncology, Barcelona, Spain.
⁵ Clinica Universidad de Navarra, Pamplona, Spain.
⁶ National Cancer Center, Goyang, South Korea.
⁷ Mayo Clinic, Rochester, MN, USA.
⁸ CHA Bundang Medical Center, CHA University, Gyeonggi-do, South Korea.
⁹ Centre François Baclesse, Caen, France.
¹⁰ Samsung Medical Center Sungkyunkwan University School of Medicine, Seoul, South Korea.
¹¹ Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
¹² Rush University Medical Center, Chicago, IL, USA.
¹³ Instituto do Câncer do Estado de São Paulo, São Paulo, Brazil.
¹⁴ Pontificia Universidad Católica de Chile, Santiago, Chile.
¹⁵ Merck & Co, Kenilworth, NJ, USA.
¹⁶ David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles, CA, USA.

PMID: 26712084
DOI: 10.1016/S0140-6736(15)01281-7

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Randomized Controlled Trial

Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial

Roy S Herbst et al. Lancet. 2016.

. 2016 Apr 9;387(10027):1540-1550. doi: 10.1016/S0140-6736(15)01281-7. Epub 2015 Dec 19. Authors Roy S Herbst¹, Paul Baas², Dong-Wan Kim³, Enriqueta Felip⁴, José L Pérez-Gracia⁵, Ji-Youn Han⁶, Julian Molina⁷, Joo-Hang Kim⁸, Catherine Dubos Arvis⁹, Myung-Ju Ahn¹⁰, Margarita Majem¹¹, Mary J Fidler¹², Gilberto de Castro Jr¹³, Marcelo Garrido¹⁴, Gregory M Lubiniecki¹⁵, Yue Shentu¹⁵, Ellie Im¹⁵, Marisa Dolled-Filhart¹⁵, Edward B Garon¹⁶ Affiliations

¹ Yale School of Medicine, Yale Cancer Center, and Smilow Cancer Hospital, New Haven, CT, USA. Electronic address: roy.herbst@yale.edu.
² The Netherlands Cancer Institute and The Academic Medical Hospital Amsterdam, Amsterdam, Netherlands.
³ Seoul National University Hospital, Seoul, South Korea.
⁴ Vall D'Hebron University Hospital and Vall d'Hebron Institute of Oncology, Barcelona, Spain.
⁵ Clinica Universidad de Navarra, Pamplona, Spain.
⁶ National Cancer Center, Goyang, South Korea.
⁷ Mayo Clinic, Rochester, MN, USA.
⁸ CHA Bundang Medical Center, CHA University, Gyeonggi-do, South Korea.
⁹ Centre François Baclesse, Caen, France.
¹⁰ Samsung Medical Center Sungkyunkwan University School of Medicine, Seoul, South Korea.
¹¹ Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
¹² Rush University Medical Center, Chicago, IL, USA.
¹³ Instituto do Câncer do Estado de São Paulo, São Paulo, Brazil.
¹⁴ Pontificia Universidad Católica de Chile, Santiago, Chile.
¹⁵ Merck & Co, Kenilworth, NJ, USA.
¹⁶ David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles, CA, USA.

PMID: 26712084
DOI: 10.1016/S0140-6736(15)01281-7

Item in Clipboard

Abstract

Background: Despite recent advances in the treatment of advanced non-small-cell lung cancer, there remains a need for effective treatments for progressive disease. We assessed the efficacy of pembrolizumab for patients with previously treated, PD-L1-positive, advanced non-small-cell lung cancer.

Methods: We did this randomised, open-label, phase 2/3 study at 202 academic medical centres in 24 countries. Patients with previously treated non-small-cell lung cancer with PD-L1 expression on at least 1% of tumour cells were randomly assigned (1:1:1) in blocks of six per stratum with an interactive voice-response system to receive pembrolizumab 2 mg/kg, pembrolizumab 10 mg/kg, or docetaxel 75 mg/m(2) every 3 weeks. The primary endpoints were overall survival and progression-free survival both in the total population and in patients with PD-L1 expression on at least 50% of tumour cells. We used a threshold for significance of p<0.00825 (one-sided) for the analysis of overall survival and a threshold of p<0.001 for progression-free survival. This trial is registered at ClinicalTrials.gov, number NCT01905657.

Findings: Between Aug 28, 2013, and Feb 27, 2015, we enrolled 1034 patients: 345 allocated to pembrolizumab 2 mg/kg, 346 allocated to pembrolizumab 10 mg/kg, and 343 allocated to docetaxel. By Sept 30, 2015, 521 patients had died. In the total population, median overall survival was 10.4 months with pembrolizumab 2 mg/kg, 12.7 months with pembrolizumab 10 mg/kg, and 8.5 months with docetaxel. Overall survival was significantly longer for pembrolizumab 2 mg/kg versus docetaxel (hazard ratio [HR] 0.71, 95% CI 0.58-0.88; p=0.0008) and for pembrolizumab 10 mg/kg versus docetaxel (0.61, 0.49-0.75; p<0.0001). Median progression-free survival was 3.9 months with pembrolizumab 2 mg/kg, 4.0 months with pembrolizumab 10 mg/kg, and 4.0 months with docetaxel, with no significant difference for pembrolizumab 2 mg/kg versus docetaxel (0.88, 0.74-1.05; p=0.07) or for pembrolizumab 10 mg/kg versus docetaxel (HR 0.79, 95% CI 0.66-0.94; p=0.004). Among patients with at least 50% of tumour cells expressing PD-L1, overall survival was significantly longer with pembrolizumab 2 mg/kg than with docetaxel (median 14.9 months vs 8.2 months; HR 0.54, 95% CI 0.38-0.77; p=0.0002) and with pembrolizumab 10 mg/kg than with docetaxel (17.3 months vs 8.2 months; 0.50, 0.36-0.70; p<0.0001). Likewise, for this patient population, progression-free survival was significantly longer with pembrolizumab 2 mg/kg than with docetaxel (median 5.0 months vs 4.1 months; HR 0.59, 95% CI 0.44-0.78; p=0.0001) and with pembrolizumab 10 mg/kg than with docetaxel (5.2 months vs 4.1 months; 0.59, 0.45-0.78; p<0.0001). Grade 3-5 treatment-related adverse events were less common with pembrolizumab than with docetaxel (43 [13%] of 339 patients given 2 mg/kg, 55 [16%] of 343 given 10 mg/kg, and 109 [35%] of 309 given docetaxel).

Interpretation: Pembrolizumab prolongs overall survival and has a favourable benefit-to-risk profile in patients with previously treated, PD-L1-positive, advanced non-small-cell lung cancer. These data establish pembrolizumab as a new treatment option for this population and validate the use of PD-L1 selection.

Funding: Merck & Co.

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