Response rate as a potential surrogate for survival and efficacy in patients treated with novel immune checkpoint inhibitors

A meta-regression of randomised prospective studies

Giandomenico Roviello, Fabrice Andre, Sergio Venturini, Barbara Pistilli, Giuseppe Curigliano, Massimo Cristofanilli, Pietro Rosellini, Daniele Generali

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Introduction To assess the role of the tumour response rate (RR) after immune checkpoint inhibitors–based therapy as a potential surrogate end-point of progression-free survival (PFS) and overall survival (OS) in patients with solid tumours, we performed a trial-based meta-regression of randomised studies comparing different immune checkpoint inhibitors–based treatments. Methods The systematic literature search included the electronic databases and the proceedings of oncologic meetings. Treatment effects on PFS and OS were expressed as hazard ratios (HRs); treatment effects on RR were expressed as odds ratios (ORs). A weighted regression analysis was performed on log-transformed treatment effect estimates to test the association between treatment effects on the surrogate outcome and treatment effects on the clinical outcome. Results Twenty-four trials, for a total of 11,894 patients, were included in the analysis. Using the complete set of data, the regression of either the log(HR) for PFS or the log(HR) for OS on the log(OR) for RR demonstrated weak associations (R2 = 0.47; 95% confidence interval [CI], 0.03–0.77; P = 0.001; and R2 = 0.32; 95% CI, 0.02–0.76; P = 0.01, respectively). The pre-planned analyses stratifying trials according to different type of disease and different mechanism of action of immune checkpoint inhibitors showed a very weak association of the RR with the OS for non–small cell lung cancer indicated and a modest association of the RR with the PFS for cytotoxic T lymphocyte–associated antigen 4 checkpoint inhibitors. Conclusion The results of the trial-based meta-regression analysis indicated a weak correlation between RR and OS, supporting future investigations to assess the surrogacy of RR in the patient treated with immune checkpoint inhibitors.

Original languageEnglish
Pages (from-to)257-265
Number of pages9
JournalEuropean Journal of Cancer
Volume86
DOIs
Publication statusPublished - Nov 1 2017

Fingerprint

Prospective Studies
Disease-Free Survival
Survival
Therapeutics
Odds Ratio
Regression Analysis
Confidence Intervals
Viral Tumor Antigens
Non-Small Cell Lung Carcinoma
Meta-Analysis
Neoplasms
Survival Rate
Biomarkers
Databases

Keywords

  • Efficacy
  • Immune checkpoint
  • Surrogate markers
  • Survival

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Response rate as a potential surrogate for survival and efficacy in patients treated with novel immune checkpoint inhibitors : A meta-regression of randomised prospective studies. / Roviello, Giandomenico; Andre, Fabrice; Venturini, Sergio; Pistilli, Barbara; Curigliano, Giuseppe; Cristofanilli, Massimo; Rosellini, Pietro; Generali, Daniele.

In: European Journal of Cancer, Vol. 86, 01.11.2017, p. 257-265.

Research output: Contribution to journalArticle

Roviello, Giandomenico ; Andre, Fabrice ; Venturini, Sergio ; Pistilli, Barbara ; Curigliano, Giuseppe ; Cristofanilli, Massimo ; Rosellini, Pietro ; Generali, Daniele. / Response rate as a potential surrogate for survival and efficacy in patients treated with novel immune checkpoint inhibitors : A meta-regression of randomised prospective studies. In: European Journal of Cancer. 2017 ; Vol. 86. pp. 257-265.
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AU - Roviello, Giandomenico

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AU - Pistilli, Barbara

AU - Curigliano, Giuseppe

AU - Cristofanilli, Massimo

AU - Rosellini, Pietro

AU - Generali, Daniele

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N2 - Introduction To assess the role of the tumour response rate (RR) after immune checkpoint inhibitors–based therapy as a potential surrogate end-point of progression-free survival (PFS) and overall survival (OS) in patients with solid tumours, we performed a trial-based meta-regression of randomised studies comparing different immune checkpoint inhibitors–based treatments. Methods The systematic literature search included the electronic databases and the proceedings of oncologic meetings. Treatment effects on PFS and OS were expressed as hazard ratios (HRs); treatment effects on RR were expressed as odds ratios (ORs). A weighted regression analysis was performed on log-transformed treatment effect estimates to test the association between treatment effects on the surrogate outcome and treatment effects on the clinical outcome. Results Twenty-four trials, for a total of 11,894 patients, were included in the analysis. Using the complete set of data, the regression of either the log(HR) for PFS or the log(HR) for OS on the log(OR) for RR demonstrated weak associations (R2 = 0.47; 95% confidence interval [CI], 0.03–0.77; P = 0.001; and R2 = 0.32; 95% CI, 0.02–0.76; P = 0.01, respectively). The pre-planned analyses stratifying trials according to different type of disease and different mechanism of action of immune checkpoint inhibitors showed a very weak association of the RR with the OS for non–small cell lung cancer indicated and a modest association of the RR with the PFS for cytotoxic T lymphocyte–associated antigen 4 checkpoint inhibitors. Conclusion The results of the trial-based meta-regression analysis indicated a weak correlation between RR and OS, supporting future investigations to assess the surrogacy of RR in the patient treated with immune checkpoint inhibitors.

AB - Introduction To assess the role of the tumour response rate (RR) after immune checkpoint inhibitors–based therapy as a potential surrogate end-point of progression-free survival (PFS) and overall survival (OS) in patients with solid tumours, we performed a trial-based meta-regression of randomised studies comparing different immune checkpoint inhibitors–based treatments. Methods The systematic literature search included the electronic databases and the proceedings of oncologic meetings. Treatment effects on PFS and OS were expressed as hazard ratios (HRs); treatment effects on RR were expressed as odds ratios (ORs). A weighted regression analysis was performed on log-transformed treatment effect estimates to test the association between treatment effects on the surrogate outcome and treatment effects on the clinical outcome. Results Twenty-four trials, for a total of 11,894 patients, were included in the analysis. Using the complete set of data, the regression of either the log(HR) for PFS or the log(HR) for OS on the log(OR) for RR demonstrated weak associations (R2 = 0.47; 95% confidence interval [CI], 0.03–0.77; P = 0.001; and R2 = 0.32; 95% CI, 0.02–0.76; P = 0.01, respectively). The pre-planned analyses stratifying trials according to different type of disease and different mechanism of action of immune checkpoint inhibitors showed a very weak association of the RR with the OS for non–small cell lung cancer indicated and a modest association of the RR with the PFS for cytotoxic T lymphocyte–associated antigen 4 checkpoint inhibitors. Conclusion The results of the trial-based meta-regression analysis indicated a weak correlation between RR and OS, supporting future investigations to assess the surrogacy of RR in the patient treated with immune checkpoint inhibitors.

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