Prognostic impact of immune-related adverse events on survival outcomes in metastatic gastrointestinal cancer: A single-institutional experience.

Abstract

801 Background: Immune checkpoint inhibitors (ICIs) have several approved indications in the treatment of gastrointestinal (GI) malignancies including metastatic disease. The adverse events related to ICI use or Immune related adverse events (irAEs) are now being more readily recognized. The association between the occurrence of irAEs and survival outcomes is not well understood. Whereas complete tolerability of ICIs with minimal irAEs may be indicative of a lack of response, the development of moderate to severe irAEs could result in significant morbidity and mortality especially in already advanced disease. This dilemma has provided an impetus to present our 5-year single institutional experience wherein we aim to determine the impact of irAEs on survival outcomes in metastatic GI malignancies. Methods: We retrospectively reviewed a cohort of adult patients who received ICIs for metastatic GI malignancies at the Cleveland Clinic foundation between 2017-2022 by utilizing an outpatient oncology pharmacy database. ICIs of interest included atezolizumab, ipilimumab, nivolumab and pembrolizumab. The occurrence of irAEs was as determined by primary oncologist. The primary and secondary outcomes were overall survival (OS) and progression free survival (PFS) in patients based on irAE presence, respectively. Results: There was a total of 151 patients who received ICIs for various metastatic GI malignancies. Among these, 38 unique irAEs were identified constituting 25% of the entire cohort. The table shows their distribution by organ system and type of GI malignancy. We observed hyper progressive disease in 3% of irAE cohort. Grade 3-4 irAEs requiring hospitalization occurred in 32% of all irAEs, median hospital length of stay of 5 (range:1-15) days with 11% resulting in death. 26 % discontinued treatment due to irAEs while 44% had palliative care consultations/hospice transition soon after. The median OS rates in patients who had irAEs vs those who didn’t, respectively, were 10 months [95% confidence interval (CI, 5-NA)] vs. 9 months [95% confidence interval (CI, 6-12)], p=0.85. There was also no statistically significant difference in median PFS between both groups (p=0.76). Conclusions: In our single institution cohort of metastatic gastrointestinal cancer patients, despite significant morbidity from irAEs, the prognosis was similar as previous studies suggesting a better outcome in patients with irAEs compared to those who did not experience irAEs.[Table: see text]