Syed A Hussain1, Alison Birtle2, Simon Crabb3, Robert Huddart4, Diane Small5, Maxwell Summerhayes5, Robert Jones6, Andrew Protheroe7. 1. Institute of Translational & Stratified Medicine, Plymouth University, Peninsula Schools of Medicine and Dentistry, Plymouth, UK. Electronic address: syed.hussain@plymouth.ac.uk. 2. Lancashire Teaching Hospitals NHS Trust, Preston, UK. 3. Southampton Experimental Cancer Medicine Centre, University of Southampton, Southampton, UK. 4. Royal Marsden NHS Foundation Trust, London, UK. 5. Roche Products Ltd., Welwyn Garden City, UK. 6. Institute of Cancer Sciences, University of Glasgow, Glasgow, UK. 7. Oxford Cancer and Haematology Centre, Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
Abstract
CONTEXT: A number of PD-1/PD-L1 inhibitors have recently been approved for use in patients with locally advanced or metastatic urothelial carcinoma (UC) on the basis of results from several clinical trials. OBJECTIVE: To review the evidence from these trials and consider what it means for the use of these drugs in first-line and post-platinum settings in real-life clinical practice. EVIDENCE ACQUISITION: PubMed was searched for full reports of clinical trials of single-agent PD-1/PD-L1 inhibitors in advanced UC. Twelve publications were included. EVIDENCE SYNTHESIS: Responses to PD-1/PD-L1 inhibitors appear to be durable but are only achieved in 17-26% of patients. These drugs offer different toxicity and efficacy profiles to standard chemotherapy regimens. This should be considered when choosing a treatment strategy for each patient. CONCLUSIONS: PD-1/PD-L1 inhibitors represent a major step forward in the management of advanced UC, although several questions remain regarding their optimal use in routine clinical practice. A validated predictive biomarker of response is yet to be defined, and this is perhaps the most significant unmet need for currently available drugs. PATIENT SUMMARY: We reviewed the results from clinical trials that investigated how well certain types of anticancer drugs called PD-1/PD-L1 inhibitors worked in patients with bladder cancer. We found that more research is required to identify (1) the factors that might predict which patients with bladder cancer will respond to PD-1/PD-L1 inhibitors and (2) the optimum duration of treatment with these drugs.
CONTEXT: A number of PD-1/PD-L1 inhibitors have recently been approved for use in patients with locally advanced or metastatic urothelial carcinoma (UC) on the basis of results from several clinical trials. OBJECTIVE: To review the evidence from these trials and consider what it means for the use of these drugs in first-line and post-platinum settings in real-life clinical practice. EVIDENCE ACQUISITION: PubMed was searched for full reports of clinical trials of single-agent PD-1/PD-L1 inhibitors in advanced UC. Twelve publications were included. EVIDENCE SYNTHESIS: Responses to PD-1/PD-L1 inhibitors appear to be durable but are only achieved in 17-26% of patients. These drugs offer different toxicity and efficacy profiles to standard chemotherapy regimens. This should be considered when choosing a treatment strategy for each patient. CONCLUSIONS: PD-1/PD-L1 inhibitors represent a major step forward in the management of advanced UC, although several questions remain regarding their optimal use in routine clinical practice. A validated predictive biomarker of response is yet to be defined, and this is perhaps the most significant unmet need for currently available drugs. PATIENT SUMMARY: We reviewed the results from clinical trials that investigated how well certain types of anticancer drugs called PD-1/PD-L1 inhibitors worked in patients with bladder cancer. We found that more research is required to identify (1) the factors that might predict which patients with bladder cancer will respond to PD-1/PD-L1 inhibitors and (2) the optimum duration of treatment with these drugs.
Authors: Juan Carlos Pardo; Vicenç Ruiz de Porras; Andrea Plaja; Cristina Carrato; Olatz Etxaniz; Oscar Buisan; Albert Font Journal: Int J Mol Sci Date: 2020-08-29 Impact factor: 5.923