Christopher J D Wallis1, Keith Lawson1, Mohit Butaney2, Raj Satkunasivam3, Jigarkumar Parikh4,5, Stephen J Freedland6,7, Sandip P Patel8, Omid Hamid9, Sumanta K Pal10, Zachary Klaassen5,11. 1. Department of Surgery, Division of Urology, University of Toronto, Toronto, ON, Canada. 2. Royal College of Surgeons in Ireland School of Medicine, Dublin, Ireland. 3. Department of Urology and Center for Outcomes Research, Houston Methodist Hospital, Houston, TX, USA. 4. Department of Hematology/Oncology, Medical College of Georgia at Augusta University, Augusta, GA, USA. 5. Georgia Cancer Center - Augusta University, Augusta, GA, USA. 6. Department of Surgery, Division of Urology, Cedars-Sinai Medical Center, Los Angeles, CA, USA. 7. Urology Section, Durham VA Medical Center, Durham NC, USA. 8. Department of Medicine, UC San Diego Moores Cancer Center - La Jolla, La Jolla, CA, USA. 9. Translational Research & Immunooncology, The Angeles Clinic & Research Institute, Los Angeles, CA, USA. 10. Department of Medical Oncology & Experimental Therapeutics, City of Hope Comprehensive Cancer Center, Duarte, CA, USA. 11. Department of Surgery, Division of Urology, Medical College of Georgia at Augusta University, Augusta, GA, USA.
Abstract
BACKGROUND: Targeting the programmed death ligand 1 (PD-L1) pathway has become standard for many advanced malignancies. Whether PD-L1 expression predicts response is unclear. We assessed the association between PD-L1 expression and immunotherapy response using stratified meta-analysis. METHODS: We performed a systematic review of randomized clinical trials published prior to October 2018 comparing overall survival (OS) in patients with advanced solid organ malignancies treated with immunotherapy or standard treatment. Pooled hazard ratios were calculated among patients with high and low PD-L1 levels independently. Differences between the two estimates were assessed using meta-analysis of study-level differences. Our primary analysis assessed a 1% threshold while secondary analyses utilized 5, 10 and 50%. RESULTS: 14 eligible trials reporting on 8887 patients were included. While there was a significant OS benefit for immunotherapy compared with standard treatment for all patients, the magnitude of benefit was significantly larger among those with high PD-L1 expression (P = 0.006). This finding persisted regardless of threshold used and across subgroup analyses according to PD-L1 assay type, tumor histology, line of therapy, type of inhibitor and study methodology. CONCLUSIONS: PD-L1 levels have important predictive value in determining the response to immunotherapy. However, patients with low PD-L1 levels also experience improved survival with immunotherapy compared with standard treatment.
BACKGROUND: Targeting the programmed death ligand 1 (PD-L1) pathway has become standard for many advanced malignancies. Whether PD-L1 expression predicts response is unclear. We assessed the association between PD-L1 expression and immunotherapy response using stratified meta-analysis. METHODS: We performed a systematic review of randomized clinical trials published prior to October 2018 comparing overall survival (OS) in patients with advanced solid organ malignancies treated with immunotherapy or standard treatment. Pooled hazard ratios were calculated among patients with high and low PD-L1 levels independently. Differences between the two estimates were assessed using meta-analysis of study-level differences. Our primary analysis assessed a 1% threshold while secondary analyses utilized 5, 10 and 50%. RESULTS: 14 eligible trials reporting on 8887 patients were included. While there was a significant OS benefit for immunotherapy compared with standard treatment for all patients, the magnitude of benefit was significantly larger among those with high PD-L1 expression (P = 0.006). This finding persisted regardless of threshold used and across subgroup analyses according to PD-L1 assay type, tumor histology, line of therapy, type of inhibitor and study methodology. CONCLUSIONS:PD-L1 levels have important predictive value in determining the response to immunotherapy. However, patients with low PD-L1 levels also experience improved survival with immunotherapy compared with standard treatment.
Authors: Christopher Ma; Rish K Pai; David F Schaeffer; Jonathan Krell; Leonardo Guizzetti; Stefanie C McFarlane; John K MacDonald; Won-Tak Choi; Roger M Feakins; Richard Kirsch; Gregory Y Lauwers; Reetesh K Pai; Christophe Rosty; Amitabh Srivastava; Joanna C Walsh; Brian G Feagan; Vipul Jairath Journal: J Immunother Cancer Date: 2022-03 Impact factor: 12.469