Pembrolizumab versus Chemotherapy for PD-L1-Positive Non-Small-Cell Lung Cancer

Martin Reck, Delvys Rodriguez-Abreu, Andrew G. Robinson, Rina Hui, Tibor Csöszi, Andrea Fülöp, Maya Gottfried, Nir Peled, Ali Tafreshi, Sinead Cuffe, Mary O'Brien, Suman Rao, Katsuyuki Hotta, Melanie A. Leiby, Gregory M. Lubiniecki, Yue Shentu, Reshma Rangwala, Julie R. Brahmer

Research output: Contribution to journalArticle

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Abstract

BACKGROUND Pembrolizumab is a humanized monoclonal antibody against programmed death 1 (PD-1) that has antitumor activity in advanced non-small-cell lung cancer (NSCLC), with increased activity in tumors that express programmed death ligand 1 (PD-L1). METHODS In this open-label, phase 3 trial, we randomly assigned 305 patients who had previously untreated advanced NSCLC with PD-L1 expression on at least 50% of tumor cells and no sensitizing mutation of the epidermal growth factor receptor gene or translocation of the anaplastic lymphoma kinase gene to receive either pembrolizumab (at a fixed dose of 200 mg every 3 weeks) or the investigator's choice of platinum-based chemotherapy. Crossover from the chemotherapy group to the pembrolizumab group was permitted in the event of disease progression. The primary end point, progression-free survival, was assessed by means of blinded, independent, central radiologic review. Secondary end points were overall survival, objective response rate, and safety. RESULTS Median progression-free survival was 10.3 months (95% confidence interval [CI], 6.7 to not reached) in the pembrolizumab group versus 6.0 months (95% CI, 4.2 to 6.2) in the chemotherapy group (hazard ratio for disease progression or death, 0.50; 95% CI, 0.37 to 0.68; P<0.001). The estimated rate of overall survival at 6 months was 80.2% in the pembrolizumab group versus 72.4% in the chemotherapy group (hazard ratio for death, 0.60; 95% CI, 0.41 to 0.89; P = 0.005). The response rate was higher in the pembrolizumab group than in the chemotherapy group (44.8% vs. 27.8%), the median duration of response was longer (not reached [range, 1.9+ to 14.5+ months] vs. 6.3 months [range, 2.1+ to 12.6+]), and treatment-related adverse events of any grade were less frequent (occurring in 73.4% vs. 90.0% of patients), as were grade 3, 4, or 5 treatment-related adverse events (26.6% vs. 53.3%). CONCLUSIONS In patients with advanced NSCLC and PD-L1 expression on at least 50% of tumor cells, pembrolizumab was associated with significantly longer progression-free and overall survival and with fewer adverse events than was platinum-based chemotherapy.

Original languageEnglish
Pages (from-to)1823-1833
Number of pages11
JournalNew England Journal of Medicine
Volume375
Issue number19
DOIs
Publication statusPublished - Nov 10 2016

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Non-Small Cell Lung Carcinoma
Ligands
Drug Therapy
Confidence Intervals
Disease-Free Survival
Platinum
Disease Progression
erbB-1 Genes
Antibodies, Monoclonal, Humanized
Neoplasms
pembrolizumab
Survival Rate
Research Personnel
Safety
Mutation
Survival
Therapeutics
Genes

ASJC Scopus subject areas

  • Medicine(all)

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Reck, M., Rodriguez-Abreu, D., Robinson, A. G., Hui, R., Csöszi, T., Fülöp, A., ... Brahmer, J. R. (2016). Pembrolizumab versus Chemotherapy for PD-L1-Positive Non-Small-Cell Lung Cancer. New England Journal of Medicine, 375(19), 1823-1833. https://doi.org/10.1056/NEJMoa1606774

Pembrolizumab versus Chemotherapy for PD-L1-Positive Non-Small-Cell Lung Cancer. / Reck, Martin; Rodriguez-Abreu, Delvys; Robinson, Andrew G.; Hui, Rina; Csöszi, Tibor; Fülöp, Andrea; Gottfried, Maya; Peled, Nir; Tafreshi, Ali; Cuffe, Sinead; O'Brien, Mary; Rao, Suman; Hotta, Katsuyuki; Leiby, Melanie A.; Lubiniecki, Gregory M.; Shentu, Yue; Rangwala, Reshma; Brahmer, Julie R.

In: New England Journal of Medicine, Vol. 375, No. 19, 10.11.2016, p. 1823-1833.

Research output: Contribution to journalArticle

Reck, M, Rodriguez-Abreu, D, Robinson, AG, Hui, R, Csöszi, T, Fülöp, A, Gottfried, M, Peled, N, Tafreshi, A, Cuffe, S, O'Brien, M, Rao, S, Hotta, K, Leiby, MA, Lubiniecki, GM, Shentu, Y, Rangwala, R & Brahmer, JR 2016, 'Pembrolizumab versus Chemotherapy for PD-L1-Positive Non-Small-Cell Lung Cancer', New England Journal of Medicine, vol. 375, no. 19, pp. 1823-1833. https://doi.org/10.1056/NEJMoa1606774
Reck M, Rodriguez-Abreu D, Robinson AG, Hui R, Csöszi T, Fülöp A et al. Pembrolizumab versus Chemotherapy for PD-L1-Positive Non-Small-Cell Lung Cancer. New England Journal of Medicine. 2016 Nov 10;375(19):1823-1833. https://doi.org/10.1056/NEJMoa1606774
Reck, Martin ; Rodriguez-Abreu, Delvys ; Robinson, Andrew G. ; Hui, Rina ; Csöszi, Tibor ; Fülöp, Andrea ; Gottfried, Maya ; Peled, Nir ; Tafreshi, Ali ; Cuffe, Sinead ; O'Brien, Mary ; Rao, Suman ; Hotta, Katsuyuki ; Leiby, Melanie A. ; Lubiniecki, Gregory M. ; Shentu, Yue ; Rangwala, Reshma ; Brahmer, Julie R. / Pembrolizumab versus Chemotherapy for PD-L1-Positive Non-Small-Cell Lung Cancer. In: New England Journal of Medicine. 2016 ; Vol. 375, No. 19. pp. 1823-1833.
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abstract = "BACKGROUND Pembrolizumab is a humanized monoclonal antibody against programmed death 1 (PD-1) that has antitumor activity in advanced non-small-cell lung cancer (NSCLC), with increased activity in tumors that express programmed death ligand 1 (PD-L1). METHODS In this open-label, phase 3 trial, we randomly assigned 305 patients who had previously untreated advanced NSCLC with PD-L1 expression on at least 50{\%} of tumor cells and no sensitizing mutation of the epidermal growth factor receptor gene or translocation of the anaplastic lymphoma kinase gene to receive either pembrolizumab (at a fixed dose of 200 mg every 3 weeks) or the investigator's choice of platinum-based chemotherapy. Crossover from the chemotherapy group to the pembrolizumab group was permitted in the event of disease progression. The primary end point, progression-free survival, was assessed by means of blinded, independent, central radiologic review. Secondary end points were overall survival, objective response rate, and safety. RESULTS Median progression-free survival was 10.3 months (95{\%} confidence interval [CI], 6.7 to not reached) in the pembrolizumab group versus 6.0 months (95{\%} CI, 4.2 to 6.2) in the chemotherapy group (hazard ratio for disease progression or death, 0.50; 95{\%} CI, 0.37 to 0.68; P<0.001). The estimated rate of overall survival at 6 months was 80.2{\%} in the pembrolizumab group versus 72.4{\%} in the chemotherapy group (hazard ratio for death, 0.60; 95{\%} CI, 0.41 to 0.89; P = 0.005). The response rate was higher in the pembrolizumab group than in the chemotherapy group (44.8{\%} vs. 27.8{\%}), the median duration of response was longer (not reached [range, 1.9+ to 14.5+ months] vs. 6.3 months [range, 2.1+ to 12.6+]), and treatment-related adverse events of any grade were less frequent (occurring in 73.4{\%} vs. 90.0{\%} of patients), as were grade 3, 4, or 5 treatment-related adverse events (26.6{\%} vs. 53.3{\%}). CONCLUSIONS In patients with advanced NSCLC and PD-L1 expression on at least 50{\%} of tumor cells, pembrolizumab was associated with significantly longer progression-free and overall survival and with fewer adverse events than was platinum-based chemotherapy.",
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T1 - Pembrolizumab versus Chemotherapy for PD-L1-Positive Non-Small-Cell Lung Cancer

AU - Reck, Martin

AU - Rodriguez-Abreu, Delvys

AU - Robinson, Andrew G.

AU - Hui, Rina

AU - Csöszi, Tibor

AU - Fülöp, Andrea

AU - Gottfried, Maya

AU - Peled, Nir

AU - Tafreshi, Ali

AU - Cuffe, Sinead

AU - O'Brien, Mary

AU - Rao, Suman

AU - Hotta, Katsuyuki

AU - Leiby, Melanie A.

AU - Lubiniecki, Gregory M.

AU - Shentu, Yue

AU - Rangwala, Reshma

AU - Brahmer, Julie R.

PY - 2016/11/10

Y1 - 2016/11/10

N2 - BACKGROUND Pembrolizumab is a humanized monoclonal antibody against programmed death 1 (PD-1) that has antitumor activity in advanced non-small-cell lung cancer (NSCLC), with increased activity in tumors that express programmed death ligand 1 (PD-L1). METHODS In this open-label, phase 3 trial, we randomly assigned 305 patients who had previously untreated advanced NSCLC with PD-L1 expression on at least 50% of tumor cells and no sensitizing mutation of the epidermal growth factor receptor gene or translocation of the anaplastic lymphoma kinase gene to receive either pembrolizumab (at a fixed dose of 200 mg every 3 weeks) or the investigator's choice of platinum-based chemotherapy. Crossover from the chemotherapy group to the pembrolizumab group was permitted in the event of disease progression. The primary end point, progression-free survival, was assessed by means of blinded, independent, central radiologic review. Secondary end points were overall survival, objective response rate, and safety. RESULTS Median progression-free survival was 10.3 months (95% confidence interval [CI], 6.7 to not reached) in the pembrolizumab group versus 6.0 months (95% CI, 4.2 to 6.2) in the chemotherapy group (hazard ratio for disease progression or death, 0.50; 95% CI, 0.37 to 0.68; P<0.001). The estimated rate of overall survival at 6 months was 80.2% in the pembrolizumab group versus 72.4% in the chemotherapy group (hazard ratio for death, 0.60; 95% CI, 0.41 to 0.89; P = 0.005). The response rate was higher in the pembrolizumab group than in the chemotherapy group (44.8% vs. 27.8%), the median duration of response was longer (not reached [range, 1.9+ to 14.5+ months] vs. 6.3 months [range, 2.1+ to 12.6+]), and treatment-related adverse events of any grade were less frequent (occurring in 73.4% vs. 90.0% of patients), as were grade 3, 4, or 5 treatment-related adverse events (26.6% vs. 53.3%). CONCLUSIONS In patients with advanced NSCLC and PD-L1 expression on at least 50% of tumor cells, pembrolizumab was associated with significantly longer progression-free and overall survival and with fewer adverse events than was platinum-based chemotherapy.

AB - BACKGROUND Pembrolizumab is a humanized monoclonal antibody against programmed death 1 (PD-1) that has antitumor activity in advanced non-small-cell lung cancer (NSCLC), with increased activity in tumors that express programmed death ligand 1 (PD-L1). METHODS In this open-label, phase 3 trial, we randomly assigned 305 patients who had previously untreated advanced NSCLC with PD-L1 expression on at least 50% of tumor cells and no sensitizing mutation of the epidermal growth factor receptor gene or translocation of the anaplastic lymphoma kinase gene to receive either pembrolizumab (at a fixed dose of 200 mg every 3 weeks) or the investigator's choice of platinum-based chemotherapy. Crossover from the chemotherapy group to the pembrolizumab group was permitted in the event of disease progression. The primary end point, progression-free survival, was assessed by means of blinded, independent, central radiologic review. Secondary end points were overall survival, objective response rate, and safety. RESULTS Median progression-free survival was 10.3 months (95% confidence interval [CI], 6.7 to not reached) in the pembrolizumab group versus 6.0 months (95% CI, 4.2 to 6.2) in the chemotherapy group (hazard ratio for disease progression or death, 0.50; 95% CI, 0.37 to 0.68; P<0.001). The estimated rate of overall survival at 6 months was 80.2% in the pembrolizumab group versus 72.4% in the chemotherapy group (hazard ratio for death, 0.60; 95% CI, 0.41 to 0.89; P = 0.005). The response rate was higher in the pembrolizumab group than in the chemotherapy group (44.8% vs. 27.8%), the median duration of response was longer (not reached [range, 1.9+ to 14.5+ months] vs. 6.3 months [range, 2.1+ to 12.6+]), and treatment-related adverse events of any grade were less frequent (occurring in 73.4% vs. 90.0% of patients), as were grade 3, 4, or 5 treatment-related adverse events (26.6% vs. 53.3%). CONCLUSIONS In patients with advanced NSCLC and PD-L1 expression on at least 50% of tumor cells, pembrolizumab was associated with significantly longer progression-free and overall survival and with fewer adverse events than was platinum-based chemotherapy.

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