Use of archival versus newly collected tumor samples for assessing PD-L1 expression and overall survival: an updated analysis of KEYNOTE-010 trial
Por:
Herbst, RS, Baas, P, Perez-Gracia, JL, Felip, E, Kim, DW, Han, JY, Molina, JR, Kim, JH, Arvis, CD, Ahn, MJ, Majem, M, Fidler, MJ, Surmont, V, de Castro, G, Garrido, M, Shentu, Y, Emancipator, K, Samkari, A, Jensen, EH, Lubiniecki, GM, Garon, EB
Publicada:
1 feb 2019
Resumen:
Background: In KEYNOTE-010, pembrolizumab versus docetaxel improved overall survival (OS) in patients with programmed death-1 protein (PD)-L1-positive advanced non-small-cell lung cancer (NSCLC). A prespecified exploratory analysis compared outcomes in patients based on PD-L1 expression in archival versus newly collected tumor samples using recently updated survival data. Patients and methods: PD-L1 was assessed centrally by immunohistochemistry (22C3 antibody) in archival or newly collected tumor samples. Patients received pembrolizumab 2 or 10 mg/kg Q3W or docetaxel 75 mg/m2 Q3W for 24 months or until progression/intolerable toxicity/other reason. Response was assessed by RECIST v1.1 every 9 weeks, survival every 2 months. Primary end points were OS and progression-free survival (PFS) in tumor proportion score (TPS) 50% and 1%; pembrolizumab doses were pooled in this analysis. Results: At date cut-off of 24 March 2017, median follow-up was 31 months (range 23-41) representing 18 additional months of follow-up from the primary analysis. Pembrolizumab versus docetaxel continued to improve OS in patients with previously treated, PD-L1-expressing advanced NSCLC; hazard ratio (HR) was 0.66 [95% confidence interval (CI): 0.57, 0.77]. Of 1033 patients analyzed, 455(44%) were enrolled based on archival samples and 578 (56%) on newly collected tumor samples. Approximately 40% of archival samples and 45% of newly collected tumor samples were PD-L1 TPS 50%. For TPS 50%, the OS HRs were 0.64 (95% CI: 0.45, 0.91) and 0.40 (95% CI: 0.28, 0.56) for archival and newly collected samples, respectively. In patients with TPS 1%, OS HRs were 0.74 (95% CI: 0.59, 0.93) and 0.59 (95% CI: 0.48, 0.73) for archival and newly collected samples, respectively. In TPS 50%, PFS HRs were similar across archival [0.63 (95% CI: 0.45, 0.89)] and newly collected samples [0.53 (95% CI: 0.38, 0.72)]. In patients with TPS 1%, PFS HRs were similar across archival [0.82 (95% CI: 0.66, 1.02)] and newly collected samples [0.83 (95% CI: 0.68, 1.02)]. Conclusion: Pembrolizumab continued to improve OS over docetaxel in intention to treat population and in subsets of patients with newly collected and archival samples.
Filiaciones:
Herbst, RS:
Yale Univ, Sch Med, Dept Med Oncol, Yale Comprehens Canc Ctr, New Haven, CT USA
Baas, P:
Netherlands Canc Inst, Dept Thorac Oncol, Amsterdam, Netherlands
Perez-Gracia, JL:
Clin Univ Navarra, Dept Oncol, Pamplona, Spain
Felip, E:
Vall dHebron Univ Hosp, Dept Oncol, Lung Canc Unit, Barcelona, Spain
Vall dHebron Inst Oncol, Barcelona, Spain
Kim, DW:
Seoul Natl Univ Hosp, Dept Internal Med, Seoul, South Korea
Han, JY:
Natl Canc Ctr, Div Translat & Clin Res, Goyang, South Korea
Molina, JR:
Mayo Clin, Dept Oncol, Rochester, MN USA
Kim, JH:
CHA Univ, Dept Med Oncol, CHA Bundang Med Ctr, Pocheon Si, Gyeonggi Do, South Korea
Arvis, CD:
Ctr Francois Baclesse, Dept Med, Caen, France
Ahn, MJ:
Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Div Hematol & Oncol,Dept Med, Seoul, South Korea
Majem, M:
Hosp Santa Creu & Sant Pau, Dept Med Oncol, Barcelona, Spain
Fidler, MJ:
Rush Univ, Med Ctr, Div Hematol Oncol, Chicago, IL 60612 USA
Surmont, V:
Univ Ziekenhuis Ghent, Dept Resp Med Thorac Oncol, Ghent, Belgium
de Castro, G:
Inst Canc Estado Sao Paulo, Dept Med Oncol, Sao Paulo, Brazil
Garrido, M:
Pontificia Univ Catolica Chile, Dept Hematooncol, Santiago, Chile
Shentu, Y:
Merck & Co Inc, Dept Clin Res, Kenilworth, NJ USA
Emancipator, K:
Merck & Co Inc, Dept Clin Res, Kenilworth, NJ USA
Samkari, A:
Merck & Co Inc, Dept Clin Res, Kenilworth, NJ USA
Jensen, EH:
Merck & Co Inc, Dept Clin Res, Kenilworth, NJ USA
Lubiniecki, GM:
Merck & Co Inc, Dept Clin Res, Kenilworth, NJ USA
Garon, EB:
Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Hematol Oncol, Los Angeles, CA 90095 USA
Green Published, Hybrid Gold
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