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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 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.

SUBMITTER: Herbst RS

PROVIDER: S-EPMC6931268 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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

Herbst R S RS Baas P P Perez-Gracia J L JL Felip E E Kim D-W DW Han J-Y JY Molina J R JR Kim J-H JH Dubos Arvis C C Ahn M-J MJ Majem M M Fidler M J MJ Surmont V V de Castro G G Garrido M M Shentu Y Y Emancipator K K Samkari A A Jensen E H EH Lubiniecki G M GM Garon E B EB

Annals of oncology : official journal of the European Society for Medical Oncology 20190201 2

<h4>Background</h4>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.<h4>Patients and methods</h4>PD-L1 was assessed centrally by immunohistochemistry (22C3 antibody) in archival or newly ...[more]

PMID: 30657853

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Project description:PurposeIMpower133 (ClinicalTrials.gov identifier: NCT02763579), a randomized, double-blind, phase I/III study, demonstrated that adding atezolizumab (anti-programmed death-ligand 1 [PD-L1]) to carboplatin plus etoposide (CP/ET) for first-line (1L) treatment of extensive-stage small-cell lung cancer (ES-SCLC) resulted in significant improvement in overall survival (OS) and progression-free survival (PFS) versus placebo plus CP/ET. Updated OS, disease progression patterns, safety, and exploratory biomarkers (PD-L1, blood-based tumor mutational burden [bTMB]) are reported.Patients and methodsPatients with untreated ES-SCLC were randomly assigned 1:1 to receive four 21-day cycles of CP (area under the curve 5 mg per mL/min intravenously [IV], day 1) plus ET (100 mg/m2 IV, days 1-3) with atezolizumab (1,200 mg IV, day 1) or placebo, and then maintenance atezolizumab or placebo until unacceptable toxicity, disease progression, or loss of clinical benefit. Tumor specimens were collected; PD-L1 testing was not required for enrollment. The two primary end points, investigator-assessed PFS and OS, were statistically significant at the interim analysis. Updated OS and PFS and exploratory biomarker analyses were conducted.ResultsPatients received atezolizumab plus CP/ET (n = 201) or placebo plus CP/ET (n = 202). At the updated analysis, median follow-up for OS was 22.9 months; 302 deaths had occurred. Median OS was 12.3 and 10.3 months with atezolizumab plus CP/ET and placebo plus CP/ET, respectively (hazard ratio, 0.76; 95% CI, 0.60 to 0.95; descriptive P = .0154). At 18 months, 34.0% and 21.0% of patients were alive in atezolizumab plus CP/ET and placebo plus CP/ET arms, respectively. Patients derived benefit from the addition of atezolizumab, regardless of PD-L1 immunohistochemistry or bTMB status.ConclusionAdding atezolizumab to CP/ET as 1L treatment for ES-SCLC continued to demonstrate improved OS and a tolerable safety profile at the updated analysis, confirming the regimen as a new standard of care. Exploratory analyses demonstrated treatment benefit independent of biomarker status.

Project description:BackgroundAn increasing number of studies have examined the ability of programmed death-ligand 1 (PD-L1) to function as a marker for tumor prognosis. However, whether PD-L1 expression is a prognostic factor for the poor outcomes in many human cancers remains controversial. This study aims to investigate the prognostic role of PD-L1 expression through a meta-analysis update of 60 studies.MethodsThe studies were identified by searching PubMed, Embase, Google Scholar, and Cochrane Library, and were assessed by further quality evaluation. The pooled hazard ratios (HRs) with 95% confidence intervals (CIs) for total and stratified analyses were calculated to investigate the association between the PD-L1 expression and the overall (OS) and disease-free (DFS) or progression-free survivals (PFS) of cancer patients. Heterogeneity and publication bias were also investigated.ResultsThe results indicated that PD-L1 overexpression can predict a poor OS (HR = 1.58, 95% CI = 1.38-1.81, P <.000) and DFS/PFS (HR = 1.72, 95% CI = 1.26-2.33, P = .001). Subgroup analyses showed that PD-L1 overexpression was significantly related to the poor OS in patients with breast (HR = 1.98, 95% CI = 1.15-3.41, P = .014), urothelial (HR = 2.24, 95% CI = 1.61-3.12, P <.000), renal (HR = 3.30, 95% CI = 2.23-4.86, P <.000), and gastric cancers (HR = 1.56, 95% CI = 1.02-2.37, P = .040). Furthermore, PD-L1 overexpresion was significantly associated with poor DFS/PFS in patients with hepatocellular carcinoma (HCC) (HR = 1.72, 95% CI = 1.21-2.46, P = .003), melanoma (HR = 3.39, 95% CI = 2.02-5.69, P <.000), and renal carcinoma, (HR = 5.04, 95% CI = 2.87-8.86, P <.000). The adverse prognostic impact of PD-L1 was observed in patients of different ethnicities.ConclusionsThe findings of this meta-analysis suggest the correlation of PD-L1 overexpression with worse OS in patients with solid tumors. However, the correlations differed according to tumor types.

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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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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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