Introduction: To assess the role of the tumour response rate (RR) after immune checkpoint inhibitorsebased 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 Z 0.47; 95% confidence interval [CI], 0.03e0.77; P Z 0.001; and R2 Z 0.32; 95% CI, 0.02e0.76; P Z 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 nonesmall cell lung cancer indicated and a modest association of the RR with the PFS for cytotoxic T lymphocyteeassociated 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.

Roviello, G., Andre, F., Venturini, S., Pistilli, B., Curigliano, G., Cristofanilli, M., Rossellini, P., Generali, D., 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, <<EUROPEAN JOURNAL OF CANCER>>, 2017; 86 (1): 257-265. [doi:10.1016/j.ejca.2017.09.018] [http://hdl.handle.net/10807/206454]

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

Venturini, Sergio
Formal Analysis
;
Generali, Daniele
2017

Abstract

Introduction: To assess the role of the tumour response rate (RR) after immune checkpoint inhibitorsebased 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 Z 0.47; 95% confidence interval [CI], 0.03e0.77; P Z 0.001; and R2 Z 0.32; 95% CI, 0.02e0.76; P Z 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 nonesmall cell lung cancer indicated and a modest association of the RR with the PFS for cytotoxic T lymphocyteeassociated 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.
2017
Inglese
Roviello, G., Andre, F., Venturini, S., Pistilli, B., Curigliano, G., Cristofanilli, M., Rossellini, P., Generali, D., 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, <<EUROPEAN JOURNAL OF CANCER>>, 2017; 86 (1): 257-265. [doi:10.1016/j.ejca.2017.09.018] [http://hdl.handle.net/10807/206454]
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10807/206454
Citazioni
  • ???jsp.display-item.citation.pmc??? 14
  • Scopus 29
  • ???jsp.display-item.citation.isi??? 28
social impact