K Bishay1, P Tandon1, S Bourassa-Blanchette2, S A Laurie3, J D McCurdy4,5. 1. Division of Gastroenterology, University of Toronto, Toronto, ON. 2. Division of Infectious Diseases, University of Calgary, Calgary, AB. 3. Division of Medical Oncology, The Ottawa Hospital, Ottawa, ON. 4. Division of Gastroenterology, The Ottawa Hospital, Ottawa, ON. 5. The Ottawa Hospital Research Institute, The Ottawa Hospital, Ottawa, ON.
Abstract
Background: Immune checkpoint inhibitors (icis), including inhibitors of PD-1, PD-L1, and ctla-4, are relatively novel therapies for lung cancer, although their use might be limited by gastrointestinal toxicity. The aim of the present study was to determine the risk of diarrhea and colitis associated with icis in lung cancer and the rates of discontinuation because of those toxicities. Methods: Electronic databases were searched for prospective trials reporting the risk of diarrhea and colitis in patients with lung cancer treated with PD-1, PD-L1, and ctla-4 inhibitors. The incidences of diarrhea and colitis and their grades were assessed clinically using standardized reporting criteria. Pooled incidence and weighted relative risk estimates for diarrhea and colitis with 95% confidence intervals (cis) were estimated using a random effects model. The incidence of discontinuations for gi toxicity was also calculated. Results: Twenty-seven studies were included: sixteen studies with PD-1 inhibitors, nine studies with PD-L1 inhibitors, and four studies combining PD-based strategies with ctla-4 inhibitors. The incidence of all-grade diarrhea was 9.1% (95% ci: 7.8% to 10.5%) for anti-PD-1 therapy and 11.0% (95% ci: 7.5% to 14.5%) for anti-PD-L1 therapy. The incidence of all-grade colitis was 0.9% (95% ci: 0.4% to 1.3%) for anti-PD-1 therapy and 0.4% (95% ci: 0.0% to 0.8%) for anti-PD-L1 therapy. The relative risk for all-grade diarrhea was higher with combination anti-PD-1 and anti-ctla-4 than with anti-PD-1 monotherapy (relative risk: 1.61; 95% ci: 1.14 to 2.29). Anti-PD-1 therapy was discontinued in 4.1% of patients with diarrhea (95% ci: 0.7% to 7.4%) and in 35.7% of those with colitis (95% ci: 0.0% to 81.1%); combination therapy was discontinued in 10.1% of patients with diarrhea (95% ci: 4.8% to 15.4%) and in 39.9% of those with colitis (95% ci: 3.9% to 75.9%). Conclusions: Diarrhea is a relatively frequently encountered gi toxicity when ici therapy is used in lung cancer treatment. Colitis is less frequently encountered, although when it does occur, it often results in therapy discontinuation. 2020 Multimed Inc.
Background: Immune checkpoint inhibitors (icis), including inhibitors of PD-1, PD-L1, and ctla-4, are relatively novel therapies for lung cancer, although their use might be limited by gastrointestinal toxicity. The aim of the present study was to determine the risk of diarrhea and colitis associated with icis in lung cancer and the rates of discontinuation because of those toxicities. Methods: Electronic databases were searched for prospective trials reporting the risk of diarrhea and colitis in patients with lung cancer treated with PD-1, PD-L1, and ctla-4 inhibitors. The incidences of diarrhea and colitis and their grades were assessed clinically using standardized reporting criteria. Pooled incidence and weighted relative risk estimates for diarrhea and colitis with 95% confidence intervals (cis) were estimated using a random effects model. The incidence of discontinuations for gi toxicity was also calculated. Results: Twenty-seven studies were included: sixteen studies with PD-1 inhibitors, nine studies with PD-L1 inhibitors, and four studies combining PD-based strategies with ctla-4 inhibitors. The incidence of all-grade diarrhea was 9.1% (95% ci: 7.8% to 10.5%) for anti-PD-1 therapy and 11.0% (95% ci: 7.5% to 14.5%) for anti-PD-L1 therapy. The incidence of all-grade colitis was 0.9% (95% ci: 0.4% to 1.3%) for anti-PD-1 therapy and 0.4% (95% ci: 0.0% to 0.8%) for anti-PD-L1 therapy. The relative risk for all-grade diarrhea was higher with combination anti-PD-1 and anti-ctla-4 than with anti-PD-1 monotherapy (relative risk: 1.61; 95% ci: 1.14 to 2.29). Anti-PD-1 therapy was discontinued in 4.1% of patients with diarrhea (95% ci: 0.7% to 7.4%) and in 35.7% of those with colitis (95% ci: 0.0% to 81.1%); combination therapy was discontinued in 10.1% of patients with diarrhea (95% ci: 4.8% to 15.4%) and in 39.9% of those with colitis (95% ci: 3.9% to 75.9%). Conclusions: Diarrhea is a relatively frequently encountered gi toxicity when ici therapy is used in lung cancer treatment. Colitis is less frequently encountered, although when it does occur, it often results in therapy discontinuation. 2020 Multimed Inc.
Authors: Scott Gettinger; Naiyer A Rizvi; Laura Q Chow; Hossein Borghaei; Julie Brahmer; Neal Ready; David E Gerber; Frances A Shepherd; Scott Antonia; Jonathan W Goldman; Rosalyn A Juergens; Scott A Laurie; Faith E Nathan; Yun Shen; Christopher T Harbison; Matthew D Hellmann Journal: J Clin Oncol Date: 2016-06-27 Impact factor: 44.544
Authors: Parul Tandon; Samuel Bourassa-Blanchette; Kirles Bishay; Simon Parlow; Scott A Laurie; Jeffrey D McCurdy Journal: J Immunother Date: 2018-04 Impact factor: 4.456
Authors: Nasser Hanna; David Johnson; Sarah Temin; Sherman Baker; Julie Brahmer; Peter M Ellis; Giuseppe Giaccone; Paul J Hesketh; Ishmael Jaiyesimi; Natasha B Leighl; Gregory J Riely; Joan H Schiller; Bryan J Schneider; Thomas J Smith; Joan Tashbar; William A Biermann; Gregory Masters Journal: J Clin Oncol Date: 2017-08-14 Impact factor: 44.544
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: Scott Antonia; Sarah B Goldberg; Ani Balmanoukian; Jamie E Chaft; Rachel E Sanborn; Ashok Gupta; Rajesh Narwal; Keith Steele; Yu Gu; Joyson J Karakunnel; Naiyer A Rizvi Journal: Lancet Oncol Date: 2016-02-06 Impact factor: 41.316
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