1. Use of archival versus newly collected tumor samples for assessing PD-L1 expression and overall survival: an updated analysis of KEYNOTE-010 trial
- Author
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Marcelo Garrido, Paul Baas, Gregory M. Lubiniecki, A. Samkari, C. Dubos Arvis, Erin Jensen, Dong Wook Kim, Margarita Majem, Mary J. Fidler, J-Y. Han, Yue Shentu, G. De Castro, Jose Luis Perez-Gracia, Veerle Surmont, Kenneth Emancipator, Myung-Ju Ahn, Enriqueta Felip, Julian R. Molina, Roy S. Herbst, Joo Hang Kim, and Edward B. Garon
- Subjects
Male ,0301 basic medicine ,Oncology ,Lung Neoplasms ,Biopsy ,Docetaxel ,Pembrolizumab ,PD-L1 expression ,B7-H1 Antigen ,0302 clinical medicine ,Carcinoma, Non-Small-Cell Lung ,Antineoplastic Combined Chemotherapy Protocols ,Medicine ,Aged, 80 and over ,education.field_of_study ,Paraffin Embedding ,Hazard ratio ,Hematology ,Middle Aged ,Prognosis ,Survival Rate ,030220 oncology & carcinogenesis ,Carcinoma, Squamous Cell ,Female ,medicine.drug ,Ciencias de la Salud::Oncología [Materias Investigacion] ,Adult ,medicine.medical_specialty ,Population ,Antibodies, Monoclonal, Humanized ,Specimen Handling ,Young Adult ,03 medical and health sciences ,Internal medicine ,Overall survival ,Humans ,Lung cancer ,education ,Aged ,Intention-to-treat analysis ,business.industry ,Tumor samples ,International Agencies ,medicine.disease ,Confidence interval ,030104 developmental biology ,business ,Follow-Up Studies - Abstract
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. Trial registration ClinicalTrials.gov: NCT01905657.
- Published
- 2019