Ramy R Saleh1, Jordan L Scott2, Nicholas Meti2, Danielle Perlon2, Rouhi Fazelzad3, Alberto Ocana4, Eitan Amir5. 1. Department of Medical Oncology, McGill University, Montreal, QC, Canada. 2. Division of Medical Oncology and Hematology, Department of Medicine, Princess Margaret Cancer Centre and the University of Toronto, Toronto, ON, Canada. 3. Information Specialist, Library and Information Services, Princess Margaret Cancer Centre, Toronto, ON, Canada. 4. Hospital Clinico San Carlos and Instituto de Investigación Sanitaria San Carlos (IdISSC), and Centro Regional de Investigaciones Biomedicas (CRIB), Centro de Investigación Biomédica en Red Cáncerci (CIBERONC), Universidad Castilla La Mancha (UCLM), Madrid, Spain. 5. Division of Medical Oncology and Hematology, Department of Medicine, Princess Margaret Cancer Centre and the University of Toronto, Toronto, ON, Canada. eitan.amir@uhn.ca.
Abstract
BACKGROUND: The programmed cell death-1/programmed cell death ligand-1 (PD-L1) pathway, which plays a crucial role in cancer immune surveillance, is the target of several approved immunotherapeutic agents and is used as a predictive biomarker in some solid tumors. However, its use as a prognostic marker (i.e., regardless of therapy used) is not established clearly with available data demonstrating inconsistent prognostic impact of PD-L1 expression in solid tumors. METHODS: We conducted a systematic literature search of electronic databases and identified publications exploring the effect of PD-L1 expression on overall survival and/or disease-free survival. Hazard ratios were pooled in a meta-analysis using generic inverse-variance and random-effects modeling. We used the Deeks method to explore subgroup differences based on disease site, stage of disease, and method of PD-L1 quantification. RESULTS: One hundred and eighty-six studies met the inclusion criteria. Programmed cell death ligand-1 expression was associated with worse overall survival (hazard ratio 1.33, 95% confidence interval 1.26-1.39; p < 0.001). There was significant heterogeneity between disease sites (subgroup p = 0.002) with pancreatic, hepatocellular, and genitourinary cancers associated with the highest magnitude of adverse outcomes. Programmed cell death ligand-1 was also associated with worse overall disease-free survival (hazard ratio 1.19, 95% confidence interval 1.09-1.30; p < 0.001). Stage of disease did not significantly affect the results (subgroup p = 0.52), nor did the method of quantification via immunohistochemistry or messenger RNA (subgroup p = 0.70). CONCLUSIONS: High expression of PD-L1 is associated with worse survival in solid tumors albeit with significant heterogeneity among tumor types. The effect is consistent in early-stage and metastatic disease and is not sensitive to method of PD-L1 quantification. These data can provide additional information for the counseling of patients with cancer about prognosis.
BACKGROUND: The programmed cell death-1/programmed cell death ligand-1 (PD-L1) pathway, which plays a crucial role in cancer immune surveillance, is the target of several approved immunotherapeutic agents and is used as a predictive biomarker in some solid tumors. However, its use as a prognostic marker (i.e., regardless of therapy used) is not established clearly with available data demonstrating inconsistent prognostic impact of PD-L1 expression in solid tumors. METHODS: We conducted a systematic literature search of electronic databases and identified publications exploring the effect of PD-L1 expression on overall survival and/or disease-free survival. Hazard ratios were pooled in a meta-analysis using generic inverse-variance and random-effects modeling. We used the Deeks method to explore subgroup differences based on disease site, stage of disease, and method of PD-L1 quantification. RESULTS: One hundred and eighty-six studies met the inclusion criteria. Programmed cell death ligand-1 expression was associated with worse overall survival (hazard ratio 1.33, 95% confidence interval 1.26-1.39; p < 0.001). There was significant heterogeneity between disease sites (subgroup p = 0.002) with pancreatic, hepatocellular, and genitourinary cancers associated with the highest magnitude of adverse outcomes. Programmed cell death ligand-1 was also associated with worse overall disease-free survival (hazard ratio 1.19, 95% confidence interval 1.09-1.30; p < 0.001). Stage of disease did not significantly affect the results (subgroup p = 0.52), nor did the method of quantification via immunohistochemistry or messenger RNA (subgroup p = 0.70). CONCLUSIONS: High expression of PD-L1 is associated with worse survival in solid tumors albeit with significant heterogeneity among tumor types. The effect is consistent in early-stage and metastatic disease and is not sensitive to method of PD-L1 quantification. These data can provide additional information for the counseling of patients with cancer about prognosis.
Authors: Edward B Garon; Naiyer A Rizvi; Rina Hui; Natasha Leighl; Ani S Balmanoukian; Joseph Paul Eder; Amita Patnaik; Charu Aggarwal; Matthew Gubens; Leora Horn; Enric Carcereny; Myung-Ju Ahn; Enriqueta Felip; Jong-Seok Lee; Matthew D Hellmann; Omid Hamid; Jonathan W Goldman; Jean-Charles Soria; Marisa Dolled-Filhart; Ruth Z Rutledge; Jin Zhang; Jared K Lunceford; Reshma Rangwala; Gregory M Lubiniecki; Charlotte Roach; Kenneth Emancipator; Leena Gandhi Journal: N Engl J Med Date: 2015-04-19 Impact factor: 91.245
Authors: T L Walunas; D J Lenschow; C Y Bakker; P S Linsley; G J Freeman; J M Green; C B Thompson; J A Bluestone Journal: Immunity Date: 1994-08 Impact factor: 31.745
Authors: Brian I Rini; Thomas Powles; Michael B Atkins; Bernard Escudier; David F McDermott; Cristina Suarez; Sergio Bracarda; Walter M Stadler; Frede Donskov; Jae Lyun Lee; Robert Hawkins; Alain Ravaud; Boris Alekseev; Michael Staehler; Motohide Uemura; Ugo De Giorgi; Begoña Mellado; Camillo Porta; Bohuslav Melichar; Howard Gurney; Jens Bedke; Toni K Choueiri; Francis Parnis; Tarik Khaznadar; Alpa Thobhani; Shi Li; Elisabeth Piault-Louis; Gretchen Frantz; Mahrukh Huseni; Christina Schiff; Marjorie C Green; Robert J Motzer Journal: Lancet Date: 2019-05-09 Impact factor: 79.321
Authors: Haidong Dong; Scott E Strome; Diva R Salomao; Hideto Tamura; Fumiya Hirano; Dallas B Flies; Patrick C Roche; Jun Lu; Gefeng Zhu; Koji Tamada; Vanda A Lennon; Esteban Celis; Lieping Chen Journal: Nat Med Date: 2002-06-24 Impact factor: 53.440
Authors: Arjun V Balar; Matthew D Galsky; Jonathan E Rosenberg; Thomas Powles; Daniel P Petrylak; Joaquim Bellmunt; Yohann Loriot; Andrea Necchi; Jean Hoffman-Censits; Jose Luis Perez-Gracia; Nancy A Dawson; Michiel S van der Heijden; Robert Dreicer; Sandy Srinivas; Margitta M Retz; Richard W Joseph; Alexandra Drakaki; Ulka N Vaishampayan; Srikala S Sridhar; David I Quinn; Ignacio Durán; David R Shaffer; Bernhard J Eigl; Petros D Grivas; Evan Y Yu; Shi Li; Edward E Kadel; Zachary Boyd; Richard Bourgon; Priti S Hegde; Sanjeev Mariathasan; AnnChristine Thåström; Oyewale O Abidoye; Gregg D Fine; Dean F Bajorin Journal: Lancet Date: 2016-12-08 Impact factor: 79.321