Giandomenico Roviello1, Fabrice Andre2, Sergio Venturini3, Barbara Pistilli2, Giuseppe Curigliano4, Massimo Cristofanilli5, Pietro Rosellini6, Daniele Generali7. 1. Medical Oncology Unit, Department of Oncology, San Donato Hospital, Via Nenni 20, 52100 Arezzo, Italy; Department of Medical, Surgery and Health Sciences, University of Trieste, Piazza Ospitale 1, 34129 Trieste, Italy. Electronic address: giandomenicoroviello@hotmail.it. 2. Department of Medical Oncology, Gustave Roussy, Villejuif, France. 3. Centre for Research on Health and Social Care Management (CeRGAS), Bocconi University, Milan, Italy. 4. Early Drugs Development for Innovative Therapies Division, European Institute of Oncology, Milan, Italy. 5. Robert H Lurie Comprehensive Cancer Center, Feinberg School of Medicine, 710 North Fairbanks Ct, Suite 8-250a, Chicago, IL, USA. 6. Unit of Medical Oncology, Department of Medicine, Surgery and Neurosciences, University of Siena, Viale Bracci - Policlinico "Le Scotte", 53100 Siena, Italy. 7. Department of Medical, Surgery and Health Sciences, University of Trieste, Piazza Ospitale 1, 34129 Trieste, Italy; Breast Cancer Unit and Translational Research Unit, ASST Cremona, Viale Concordia 1, 26100 Cremona, Italy.
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.
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.
Authors: Fausto Petrelli; Michele Ghidini; Antonio Costanzo; Valentina Rampulla; Antonio Varricchio; Gianluca Tomasello Journal: Ann Transl Med Date: 2019-04