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, P. Baas, J. L. Perez-Gracia, E. Felip, D. W. Kim, J. Y. Han, Julian R Molina, J. H. Kim, C. Dubos Arvis, M. J. Ahn, M. Majem, M. J. Fidler, V. Surmont, G. De Castro, M. Garrido, Y. Shentu, K. Emancipator, A. Samkari, E. H. Jensen, G. M. LubinieckiE. B. Garon

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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/m 2 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.

Original languageEnglish (US)
Pages (from-to)281-289
Number of pages9
JournalAnnals of Oncology
Volume30
Issue number2
DOIs
StatePublished - Feb 1 2019

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docetaxel
Confidence Intervals
Survival
Neoplasms
Proteins
Disease-Free Survival
Non-Small Cell Lung Carcinoma
Immunohistochemistry
pembrolizumab
Antibodies
Population

Keywords

  • Pd-l1 expression
  • Pembrolizumab
  • Tumor samples

ASJC Scopus subject areas

  • Hematology
  • Oncology

Cite this

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.; Baas, P.; Perez-Gracia, J. L.; Felip, E.; Kim, D. W.; Han, J. Y.; Molina, Julian R; Kim, J. H.; Dubos Arvis, C.; Ahn, M. J.; Majem, M.; Fidler, M. J.; Surmont, V.; De Castro, G.; Garrido, M.; Shentu, Y.; Emancipator, K.; Samkari, A.; Jensen, E. H.; Lubiniecki, G. M.; Garon, E. B.

In: Annals of Oncology, Vol. 30, No. 2, 01.02.2019, p. 281-289.

Research output: Contribution to journalArticle

Herbst, RS, Baas, P, Perez-Gracia, JL, Felip, E, Kim, DW, Han, JY, Molina, JR, Kim, JH, Dubos Arvis, C, Ahn, MJ, Majem, M, Fidler, MJ, Surmont, V, De Castro, G, Garrido, M, Shentu, Y, Emancipator, K, Samkari, A, Jensen, EH, Lubiniecki, GM & Garon, EB 2019, 'Use of archival versus newly collected tumor samples for assessing PD-L1 expression and overall survival: An updated analysis of keynote-010 trial', Annals of Oncology, vol. 30, no. 2, pp. 281-289. https://doi.org/10.1093/annonc/mdy545
Herbst, R. S. ; Baas, P. ; Perez-Gracia, J. L. ; Felip, E. ; Kim, D. W. ; Han, J. Y. ; Molina, Julian R ; Kim, J. H. ; Dubos Arvis, C. ; Ahn, M. J. ; Majem, M. ; Fidler, M. J. ; Surmont, V. ; De Castro, G. ; Garrido, M. ; Shentu, Y. ; Emancipator, K. ; Samkari, A. ; Jensen, E. H. ; Lubiniecki, G. M. ; Garon, E. B. / Use of archival versus newly collected tumor samples for assessing PD-L1 expression and overall survival : An updated analysis of keynote-010 trial. In: Annals of Oncology. 2019 ; Vol. 30, No. 2. pp. 281-289.
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title = "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/m 2 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",
author = "Herbst, {R. S.} and P. Baas and Perez-Gracia, {J. L.} and E. Felip and Kim, {D. W.} and Han, {J. Y.} and Molina, {Julian R} and Kim, {J. H.} and {Dubos Arvis}, C. and Ahn, {M. J.} and M. Majem and Fidler, {M. J.} and V. Surmont and {De Castro}, G. and M. Garrido and Y. Shentu and K. Emancipator and A. Samkari and Jensen, {E. H.} and Lubiniecki, {G. M.} and Garon, {E. B.}",
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TY - JOUR

T1 - Use of archival versus newly collected tumor samples for assessing PD-L1 expression and overall survival

T2 - An updated analysis of keynote-010 trial

AU - Herbst, R. S.

AU - Baas, P.

AU - Perez-Gracia, J. L.

AU - Felip, E.

AU - Kim, D. W.

AU - Han, J. Y.

AU - Molina, Julian R

AU - Kim, J. H.

AU - Dubos Arvis, C.

AU - Ahn, M. J.

AU - Majem, M.

AU - Fidler, M. J.

AU - Surmont, V.

AU - De Castro, G.

AU - Garrido, M.

AU - Shentu, Y.

AU - Emancipator, K.

AU - Samkari, A.

AU - Jensen, E. H.

AU - Lubiniecki, G. M.

AU - Garon, E. B.

PY - 2019/2/1

Y1 - 2019/2/1

N2 - 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/m 2 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.

AB - 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/m 2 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.

KW - Pd-l1 expression

KW - Pembrolizumab

KW - Tumor samples

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