Immune checkpoint inhibitors (ICIs) have revolutionised the treatment of many cancers, but their use has been associated with the development of gastrointestinal (GI) toxicities such as colitis and hepatitis.
A multi-center retrospective study across 12 National Health Service centers across the United Kingdom (UK) was conducted by the UK National Oncology Trainees Collaborative for Healthcare Research (NOTCH) over a 2-year period. The study included patients receiving ICIs for malignant melanoma, non-small lung cancer and renal cell cancer as standard of care. Occurrence of clinically significant (≥grade 2) GI toxicity was assessed and correlated with subsequent treatment and outcomes. Multiple logistic regression was used to assess correlation. For overall survival (OS), Kaplan-Meier and log-rank tests were utilised.
The cohort included 2049 patients. 1230 (60%) were male with a median age of 66. Colitis occurred in 182 (8.9%) patients and hepatitis in 129 (6.3%). Of the patients where treatment was recorded, 129 (70.9%) received treatment with systemic steroids alone and 37 (20.3%) required second-line immunosuppressants (IS) in the colitis group. In the hepatitis group, 101 (78.3%) had steroids alone with 19 (14.7%) having IS. Improved OS was found in patients who experienced colitis (HR 2.59 95%CI: 2.15 to 3.11, p<0.0001) and hepatitis (HR 2.26, 95%CI: 1.84 to 2.79, p=<0.0001) compared to those with no adverse events. Pre-existing autoimmune disease (p=0.02) and combination ICIs (p=0.006) were predictors of colitis that required IS whilst grade 2 and 3 hepatitis (p<0.001) were predictors of hepatitis needing IS. The use of IS did not affect OS significantly in the colitis group (p=0.372) but did correlate with survival in the hepatitis group (p=0.037). Patients that were able to continue treatment with ICIs after toxicity had an increased OS in both groups (p<0.001).
Patients with GI toxicity following treatment with ICIs have improved OS. The use of IS did not significantly affect OS which suggests they should continue to be utilised in the treatment of GI toxicity.
United Kingdom National Oncology Trainees Collaborative for Healthcare Research (NOTCH).
Has not received any funding.
M. Swaminathan: Financial Interests, Institutional, Funding: Eli Lilly, Roche, UCB, Novartis, Medical Research Council. M. Baxter: Financial Interests, Personal, Other, Honoraria, travel, accommodation and expenses: Ipsen. D.J. Hughes: Financial Interests, Personal, Other, Honoraria: Novartis, Pfizer; Financial Interests, Institutional, Funding: NanoMab. R. Lee: Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Advisory Board: Pierre Fabre; Financial Interests, Institutional, Research Grant: Bristol Myers Squibb, AstraZeneca; Financial Interests, Institutional, Research Grant, Funding for translational research: Pierre Fabre; Financial Interests, Institutional, Other, Advisory role - payment going to research account in melanoma team: Lumisphere Technology. M. Pritchard: Financial Interests, Personal, Other, Consultancy funding: Ipsen, Mayoly Spindler Laboratories; Financial Interests, Personal, Other, Consultancy Funding: Advance Accelerator Application; Financial Interests, Institutional, Funding: Trio Medicines, Ltd. M.P. Rowe: Financial Interests, Personal, Other, Honoraria: MSD; Financial Interests, Personal, Speaker’s Bureau: Servier; Financial Interests, Personal, Other, Travel, accommodation, expenses: Astellas Pharma. A.C. Olsson-Brown: Financial Interests, Personal, Other, Honoraria: Bristol Myers Squibb; Financial Interests, Personal, Speaker’s Bureau: Bristol Myers Squibb; Financial Interests, Personal, Advisory Role: Bristol Myers Squibb, MSC Oncology; Financial Interests, Personal, Other, Honoraria, travel, accommodation and expenses: Roche; Financial Interests, Institutional, Funding: Roche, Lilly, UCB; Financial Interests, Personal, Funding: Novartis; Financial Interests, Personal, Other, Travel, accommodation and expenses: Servier. All other authors have declared no conflicts of interest.