Barbara Melosky1, Quincy Chu2, Rosalyn Juergens2, Natasha Leighl2, Deanna McLeod2, Vera Hirsh2. 1. Barbara Melosky, British Columbia Cancer Agency, Vancouver Centre, Vancouver, British Columbia; Quincy Chu, Cross Cancer Institute and University of Alberta, Edmonton, Alberta; Rosalyn Juergens, McMaster University, Juravinski Cancer Centre, Hamilton; Natasha Leighl, Princess Margaret Hospital and University of Toronto; Deanna McLeod, Kaleidoscope Strategic, Toronto, Ontario; and Vera Hirsh, Montreal General Hospital, Royal Victoria Hospital, and McGill University, Montreal, Quebec, Canada. bmelosky@bccancer.bc.ca. 2. Barbara Melosky, British Columbia Cancer Agency, Vancouver Centre, Vancouver, British Columbia; Quincy Chu, Cross Cancer Institute and University of Alberta, Edmonton, Alberta; Rosalyn Juergens, McMaster University, Juravinski Cancer Centre, Hamilton; Natasha Leighl, Princess Margaret Hospital and University of Toronto; Deanna McLeod, Kaleidoscope Strategic, Toronto, Ontario; and Vera Hirsh, Montreal General Hospital, Royal Victoria Hospital, and McGill University, Montreal, Quebec, Canada.
Abstract
PURPOSE: Non-small-cell lung cancer (NSCLC) is globally prevalent and associated with high rates of mortality. Immune checkpoint pathways are often exploited by tumors to evade immunity-mediated destruction, and checkpoint inhibitors can reactivate tumor-related immune responses. This review considers available clinical evidence for the use of checkpoint inhibitors in the treatment of second-line advanced NSCLC. METHODS: Our systematic search revealed 20 clinical trials evaluating checkpoint inhibitors in the second-line setting, three of which were randomized trials comparing programmed cell death protein 1 and programmed death ligand 1 (PD-L1) inhibitors to docetaxel, the current standard of care in this setting. RESULTS: A randomized phase II trial comparing the PD-L1 inhibitor atezolizumab to docetaxel did not demonstrate improved survival for atezolizumab in patients overall, although a trend toward improved survival with increased PD-L1 expression was apparent. Twin phase III trials showed significantly improved survival for the programmed cell death protein 1 inhibitor nivolumab compared with docetaxel in patients with both squamous and nonsquamous disease. PD-L1 expression correlated with improved survival in patients with nonsquamous disease, and patients with low levels of PD-L1 expression (< 10%) and those with EGFR mutations are unlikely to benefit. Checkpoint inhibitor therapy is generally well tolerated and associated with low rates of grade 3 or 4 adverse events compared with standard care. CONCLUSION: Level 1 evidence exists to support the use of nivolumab as second-line treatment of patients with squamous advanced NSCLC, as well as in select patients with nonsquamous disease. Benefits remain unknown in patients with targetable driver mutations, and use of PD-L1 expression to guide therapy remains controversial. Results from ongoing randomized trials evaluating biomarkers and other checkpoint inhibitors will further our understanding of this rapidly evolving area of oncology.
PURPOSE:Non-small-cell lung cancer (NSCLC) is globally prevalent and associated with high rates of mortality. Immune checkpoint pathways are often exploited by tumors to evade immunity-mediated destruction, and checkpoint inhibitors can reactivate tumor-related immune responses. This review considers available clinical evidence for the use of checkpoint inhibitors in the treatment of second-line advanced NSCLC. METHODS: Our systematic search revealed 20 clinical trials evaluating checkpoint inhibitors in the second-line setting, three of which were randomized trials comparing programmed cell death protein 1 and programmed death ligand 1 (PD-L1) inhibitors to docetaxel, the current standard of care in this setting. RESULTS: A randomized phase II trial comparing the PD-L1 inhibitor atezolizumab to docetaxel did not demonstrate improved survival for atezolizumab in patients overall, although a trend toward improved survival with increased PD-L1 expression was apparent. Twin phase III trials showed significantly improved survival for the programmed cell death protein 1 inhibitor nivolumab compared with docetaxel in patients with both squamous and nonsquamous disease. PD-L1 expression correlated with improved survival in patients with nonsquamous disease, and patients with low levels of PD-L1 expression (< 10%) and those with EGFR mutations are unlikely to benefit. Checkpoint inhibitor therapy is generally well tolerated and associated with low rates of grade 3 or 4 adverse events compared with standard care. CONCLUSION: Level 1 evidence exists to support the use of nivolumab as second-line treatment of patients with squamous advanced NSCLC, as well as in select patients with nonsquamous disease. Benefits remain unknown in patients with targetable driver mutations, and use of PD-L1 expression to guide therapy remains controversial. Results from ongoing randomized trials evaluating biomarkers and other checkpoint inhibitors will further our understanding of this rapidly evolving area of oncology.
Authors: S A Laurie; S Banerji; N Blais; S Brule; P K Cheema; P Cheung; N Daaboul; D Hao; V Hirsh; R Juergens; J Laskin; N Leighl; R MacRae; G Nicholas; D Roberge; J Rothenstein; D J Stewart; M S Tsao Journal: Curr Oncol Date: 2019-02-01 Impact factor: 3.677
Authors: R A Juergens; C Mariano; J Jolivet; N Finn; J Rothenstein; M N Reaume; A Faghih; C Labbé; S Owen; F A Shepherd; J Villeneuve; F Romeyer; F Pettersson; C Butts Journal: Curr Oncol Date: 2018-12-01 Impact factor: 3.677
Authors: Barbara Melosky; Parneet K Cheema; Anthony Brade; Deanna McLeod; Geoffrey Liu; Paul Wheatley Price; Kevin Jao; Devin D Schellenberg; Rosalyn Juergens; Natasha Leighl; Quincy Chu Journal: Oncologist Date: 2020-09-23
Authors: Leora Horn; David R Spigel; Everett E Vokes; Esther Holgado; Neal Ready; Martin Steins; Elena Poddubskaya; Hossein Borghaei; Enriqueta Felip; Luis Paz-Ares; Adam Pluzanski; Karen L Reckamp; Marco A Burgio; Martin Kohlhäeufl; David Waterhouse; Fabrice Barlesi; Scott Antonia; Oscar Arrieta; Jérôme Fayette; Lucio Crinò; Naiyer Rizvi; Martin Reck; Matthew D Hellmann; William J Geese; Ang Li; Anne Blackwood-Chirchir; Diane Healey; Julie Brahmer; Wilfried E E Eberhardt Journal: J Clin Oncol Date: 2017-10-12 Impact factor: 44.544
Authors: Vanda Téglási; Lilla Reiniger; Katalin Fábián; Orsolya Pipek; Irén Csala; Attila G Bagó; Péter Várallyai; Laura Vízkeleti; Lívia Rojkó; József Tímár; Balázs Döme; Zoltán Szállási; Charles Swanton; Judit Moldvay Journal: Neuro Oncol Date: 2017-08-01 Impact factor: 12.300
Authors: Corey A Carter; Bryan Oronsky; Scott Caroen; Jan Scicinski; Pedro Cabrales; Aiste Degesys; Christina Brzezniak Journal: Respir Med Case Rep Date: 2016-04-24