Use of archival versus newly collected tumor samples for assessing PD-L1 expression and overall survival: an updated analysis of KEYNOTE-010 trial |
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| Institution: | 1. Department of Medical Oncology, Yale University School of Medicine, Yale Comprehensive Cancer Center, New Haven, USA;2. Department of Thoracic Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands;3. Department of Oncology, Clinica Universidad de Navarra, Pamplona, Spain;4. Lung Cancer Unit, Department of Oncology, Vall d’Hebron University Hospital, Barcelona, Spain;5. Vall d''Hebron Institute of Oncology, Barcelona, Spain;6. Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea;7. Division of Translational & Clinical Research, National Cancer Center, Goyang, Republic of Korea;8. Department of Oncology, Mayo Clinic, Rochester, USA;9. Department of Medical Oncology, CHA Bundang Medical Center, CHA University, Gyeonggi-Do, Republic of Korea;10. Department of Medicine, Centre François Baclesse, Caen, France;11. Division of Hematology and Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea;12. Department of Medical Oncology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain;13. Division of Hematology Oncology, Rush University Medical Center, Chicago, USA;14. Department of Respiratory Medicine/Thoracic Oncology, Universitar Ziekenhuis Ghent, Ghent, Belgium;15. Department of Medical Oncology, Instituto do Câncer do Estado de São Paulo, Sao Paulo, Brazil;16. Department of Hemato-Oncology, Pontificia Universidad Católica de Chile, Santiago, Chile;17. Department of Clinical Research, Merck & Co. Inc., Kenilworth, USA;18. Department of Medicine, Division of Hematology/Oncology, David Geffen School of Medicine at UCLA, Los Angeles, USA |
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| Abstract: | BackgroundIn 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 methodsPD-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.ResultsAt 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)].ConclusionPembrolizumab continued to improve OS over docetaxel in intention to treat population and in subsets of patients with newly collected and archival samples.Trial registrationClinicalTrials.gov: NCT01905657. |
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