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Clinical Trial
. 2019 Feb 1;30(2):281-289.
doi: 10.1093/annonc/mdy545.

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

R S Herbst  1 , P Baas  2 , J L Perez-Gracia  3 , E Felip  4 , D-W Kim  5 , J-Y Han  6 , J R Molina  7 , J-H Kim  8 , C Dubos Arvis  9 , M-J Ahn  10 , M Majem  11 , M J Fidler  12 , V Surmont  13 , G de Castro Jr  14 , M Garrido  15 , Y Shentu  16 , K Emancipator  16 , A Samkari  16 , E H Jensen  16 , G M Lubiniecki  16 , E B Garon  17
Affiliations
Clinical Trial

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

R S Herbst et al. Ann Oncol. .

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.

Keywords: PD-L1 expression; pembrolizumab; tumor samples.

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Figures

Figure 1.
Figure 1.
(A) Prevalence of archival and newly collected tumor samples used for assessment of PD-L1 expression by histology. (B) Prevalence of PD-L1 TPS ≥50% and TPS 1%–49% in archival and newly collected tumor samples.
Figure 2.
Figure 2.
Kaplan–Meier estimates of (A) overall survival (OS) and (B) progression-free survival (PFS) for the ITT population (TPS ≥50%), and (C) OS and (D) PFS for the ITT population (TPS ≥1%) and (E) OS and (F) PFS for the ITT population (TPS 1%–49%). ITT, intention to treat.
Figure 3.
Figure 3.
Kaplan–Meier estimates of overall survival for archival and newly collected tumor samples presented by PD-L1 TPS. (A) Archival tumor samples, TPS ≥50%. (B) Newly collected tumor samples, TPS ≥50%. (C) Archival tumor samples, TPS ≥1%. (D) Newly collected tumor samples, TPS ≥1%.
Figure 4.
Figure 4.
Kaplan–Meier estimates of progression-free survival for archival and newly collected tumor samples presented by PD-L1 TPS. (A) Archival tumor samples, TPS ≥50%. (B) Newly collected tumor samples, TPS ≥50%. (C) Archival tumor samples, TPS ≥1%. (D) Newly collected tumor samples, TPS ≥1%.
Figure 5.
Figure 5.
Overall response rate (95% CI) for archival and newly collected tumor samples presented by PD-L1 TPS ≥50% and TPS ≥1%. ITT, intention to treat.
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Comment in

References

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