التفاصيل البيبلوغرافية
| العنوان: |
Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial. |
| المؤلفون: |
Herbst, Roy S.1 roy.herbst@yale.edu, Baas, Paul2, Dong-Wan Kim3, Felip, Enriqueta4, Pérez-Gracia, José L.5, Ji-Youn Han6, Molina, Julian7, Joo-Hang Kim8, Dubos Arvis, Catherine9, Myung-Ju Ahn10, Majem, Margarita11, Fidler, Mary J.12, de Castro Jr., Gilberto13, Garrido, Marcelo14, Lubiniecki, Gregory M.15, Yue Shentu15, Im, Ellie15, Dolled-Filhart, Marisa15, Garon, Edward B.16, Kim, Dong-Wan17 (AUTHOR) |
| المصدر: |
Lancet. 4/9/2016, Vol. 387 Issue 10027, p1540-1550. 11p. 1 Diagram, 2 Charts, 4 Graphs. |
| مصطلحات موضوعية: |
*PEMBROLIZUMAB, *DOCETAXEL, *CANCER treatment, *NON-small-cell lung carcinoma, *DRUG efficacy, *RANDOMIZED controlled trials, *ANTIGEN analysis, *THERAPEUTIC use of monoclonal antibodies, *ANTINEOPLASTIC agents, *DRUG therapy, *COMPARATIVE studies, *DRUG administration, *GENES, *LUNG cancer, *HYDROCARBONS, *LUNG tumors, *RESEARCH methodology, *MEDICAL cooperation, *MONOCLONAL antibodies, *PROGNOSIS, *RESEARCH, *EVALUATION research, *TREATMENT effectiveness, *PATIENT selection, *KAPLAN-Meier estimator, *THERAPEUTICS |
| مستخلص: |
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. [ABSTRACT FROM AUTHOR] |
| قاعدة البيانات: |
Academic Search Index |
