Scot A Niglio1, Rachel Jia2, Jiayi Ji2, Samuel Ruder3, Vaibhav G Patel1, Alberto Martini4, John P Sfakianos4, Kathryn E Marqueen1, Nikhil Waingankar4, Reza Mehrazin4, Peter Wiklund5, William K Oh1, Madhu Mazumdar2, Bart S Ferket2, Matthew D Galsky6. 1. Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. 2. Institute for Health Care Delivery Science, Population Health Science and Policy, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. 3. Internal Medicine, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. 4. Urology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. 5. Urology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Urology, Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden. 6. Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Electronic address: matthew.galsky@mssm.edu.
Abstract
CONTEXT: Several anti-programmed death-1 (anti-PD-1) and anti-programmed death ligand-1 (anti-PD-L1) antibodies have been approved by regulatory authorities for treatment of platinum-resistant metastatic urothelial cancer (mUC). The impact of these therapies on survival, and comparability of PD-1 versus PD-L1 blockade are unknown. OBJECTIVE: To determine the restricted mean survival time (RMST) of patients with platinum-resistant mUC treated with PD-1/PD-L1 inhibitors and to compare RMSTs in patients treated with PD-1 versus PD-L1 inhibitors. EVIDENCE ACQUISITION: We searched for phase 1, 2, and 3 clinical trials that assessed PD-1 or PD-L1 inhibition for patients with platinum-resistant mUC. Literature review and study selection, data abstraction, and risk of bias assessment were performed by two reviewers. Survival data were reconstructed using an algorithm that derives individual time-to-event data from published Kaplan-Meier curves. The RMST with 95% confidence interval (CIs) was calculated. EVIDENCE SYNTHESIS: From 836 references, six clinical trials were included. Survival data were reconstructed for 1315 and 736 patients treated with PD-1/PD-L1 inhibitors and chemotherapy, respectively. The RMSTs with PD-1/PD-L1 blockade up to 12 and 18mo of follow-up were 7.8mo (95% CI 7.6, 8.1) and 10mo (95% CI 9.7, 10.5), respectively. A network meta-analysis of two randomized trials revealed no significant difference in the RMST up to 18mo with PD-1 versus PD-L1 blockade (1.0mo; 95% CI -0.5, 2.3mo). Using reconstructed survival data from all six trials, the RMSTs with PD-1 versus PD-L1 blockade up to 12 and 18mo follow-up were 7.8mo (95% CI 7.7, 8.2) versus 7.8mo (95% CI 7.5, 8.2) and 10.1mo (95% CI 9.6, 10.7) versus 10mo (95% CI 9.5, 10.6), respectively. CONCLUSIONS: Our RMST estimates may be used as benchmarks to contextualize survival outcomes and inform future trial design with PD-1/PD-L1 inhibitors. PD-1 versus PD-L1 blockade in patients with mUC yields comparable survival outcomes. PATIENT SUMMARY: In this study, we found that outcomes for patients with metastatic bladder cancer treated with programmed death-1 and programmed death ligand-1 inhibitors, who received prior platinum-based chemotherapy, were similar.
CONTEXT: Several anti-programmed death-1 (anti-PD-1) and anti-programmed death ligand-1 (anti-PD-L1) antibodies have been approved by regulatory authorities for treatment of platinum-resistant metastatic urothelial cancer (mUC). The impact of these therapies on survival, and comparability of PD-1 versus PD-L1 blockade are unknown. OBJECTIVE: To determine the restricted mean survival time (RMST) of patients with platinum-resistant mUC treated with PD-1/PD-L1 inhibitors and to compare RMSTs in patients treated with PD-1 versus PD-L1 inhibitors. EVIDENCE ACQUISITION: We searched for phase 1, 2, and 3 clinical trials that assessed PD-1 or PD-L1 inhibition for patients with platinum-resistant mUC. Literature review and study selection, data abstraction, and risk of bias assessment were performed by two reviewers. Survival data were reconstructed using an algorithm that derives individual time-to-event data from published Kaplan-Meier curves. The RMST with 95% confidence interval (CIs) was calculated. EVIDENCE SYNTHESIS: From 836 references, six clinical trials were included. Survival data were reconstructed for 1315 and 736 patients treated with PD-1/PD-L1 inhibitors and chemotherapy, respectively. The RMSTs with PD-1/PD-L1 blockade up to 12 and 18mo of follow-up were 7.8mo (95% CI 7.6, 8.1) and 10mo (95% CI 9.7, 10.5), respectively. A network meta-analysis of two randomized trials revealed no significant difference in the RMST up to 18mo with PD-1 versus PD-L1 blockade (1.0mo; 95% CI -0.5, 2.3mo). Using reconstructed survival data from all six trials, the RMSTs with PD-1 versus PD-L1 blockade up to 12 and 18mo follow-up were 7.8mo (95% CI 7.7, 8.2) versus 7.8mo (95% CI 7.5, 8.2) and 10.1mo (95% CI 9.6, 10.7) versus 10mo (95% CI 9.5, 10.6), respectively. CONCLUSIONS: Our RMST estimates may be used as benchmarks to contextualize survival outcomes and inform future trial design with PD-1/PD-L1 inhibitors. PD-1 versus PD-L1 blockade in patients with mUC yields comparable survival outcomes. PATIENT SUMMARY: In this study, we found that outcomes for patients with metastatic bladder cancer treated with programmed death-1 and programmed death ligand-1 inhibitors, who received prior platinum-based chemotherapy, were similar.
Authors: Guru Sonpavde; Juliane Manitz; Chen Gao; Darren Tayama; Constanze Kaiser; Daniel Hennessy; Doris Makari; Ashok Gupta; Shaad Essa Abdullah; Guenter Niegisch; Jonathan E Rosenberg; Dean F Bajorin; Petros Grivas; Andrea B Apolo; Robert Dreicer; Noah M Hahn; Matthew D Galsky; Andrea Necchi; Sandy Srinivas; Thomas Powles; Toni K Choueiri; Gregory R Pond Journal: J Urol Date: 2020-06-18 Impact factor: 7.450
Authors: Marco Bandini; Jeffrey S Ross; Daniele Raggi; Andrea Gallina; Maurizio Colecchia; Roberta Lucianò; Patrizia Giannatempo; Elena Farè; Filippo Pederzoli; Marco Bianchi; Renzo Colombo; Giorgio Gandaglia; Nicola Fossati; Laura Marandino; Umberto Capitanio; Federico Deho'; Siraj M Ali; Russell Madison; Jon H Chung; Andrea Salonia; Alberto Briganti; Francesco Montorsi; Andrea Necchi Journal: J Natl Cancer Inst Date: 2021-01-04 Impact factor: 13.506