Use of archival versus newly collected tumor samples for assessing PD-L1 expression and overall survival: An updated analysis of KEYNOTE-010 trial

Abstract

Background

In KEYNOTE-010, pembrolizumab versus docetaxel improved OS in patients with 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 PFS in TPS ≥50% and ≥1%; pembrolizumab doses were pooled in this analysis.

Results

At date cutoff of March 24, 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; HR was 0.66 (95% 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 ITT population and in subsets of patients with newly collected and archival samples. [Trial Registration: ClinicalTrials.gov: NCT01905657]

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