951 Immune Checkpoint Inhibitors-Related Gastrointestinal Toxicity Is Associated With Better Overall Survival and Treatment Response in Cancer Patients

Abstract

INTRODUCTION: Immune checkpoint inhibitors (iCPI) have recently gained an essential role in treating cancer at advanced stages. However, it has been associated with the development of gastrointestinal immune-related adverse events (GI-IrAEs). We aimed in our study to assess the incidence and nature of GI-IrAEs as well as to investigate the effects of developing GI-IrAEs on cancer response to iCPI and overall survival. METHODS: We retrospectively identified adult patients diagnosed with end-stage malignancy who were treated with any iCPI at our tertiary center between 8/2014 and 8/2017. Charts were reviewed for baseline characteristics, immunotherapy regimens, response to treatment, development of GI-IrAEs, and patient’s overall 1-year survival. Patients in whom the etiology of GI-IrAEs was unclear were excluded. The overall 1-year survival was calculated from the date of treatment initiation and estimated by the Kaplan-Meier method. RESULTS: We included 492 patients with end-stage cancer receiving iCPI. The majority of patients were white 451(92%) with a median age of 64.5 years. (Table 1) GI-IrAEs were in the form of autoimmune hepatitis 18(48.5%), autoimmune colitis 16(43.5%), autoimmune pancreatitis 4 (11%), and a combination of autoimmune colitis and hepatitis in 1 patient. (Figure 1) Brain cancer was associated with the highest risk of GI-IrAEs 16 (44.4%) followed by renal cell carcinoma 7 (19.4%). Nivulomab was associated with the highest risk for GI-IrAEs (55.6%) followed by Pembrulizumab 14 (38.9%). Forty-one percent of Patients who developed GI-IrAEs had an adequate cancer response to immunotherapy compared to 25.7% in patients without GI-IrAEs (P-value = 0.022). Eighty- three percent of patients whose cancer responded to iCPI survived at 1 year compared to 36 % among non-responders (P < 0.0001). Seventy-eight percent of patients who developed GI-IrAEs survived at 1 year compared to 53% in patients without GI-IrAEs (P < 0.005). CONCLUSION: The incidence of gastrointestinal toxicity associated with iCPI is second only in frequency to dermatological toxicity. In our study, among the white population with end-stage cancer receiving iCPI, autoimmune hepatitis, colitis, and pancreatitis were fairly common and associated with better cancer response to immunotherapy and overall survival at 1 year. GI-IrAEs might be an indicator of immune system activation, thus may be a reason to continue, rather than discontinue, immunotherapy agents as tolerated.

Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: ASCO Guideline Update

“…81,82 Preliminary data suggest that GI toxicities are associated with improved survival and treatment outcomes in comparison to other immunotherapy treated patients. 86,87…”

“…81,82 Preliminary data suggest that GI toxicities are associated with improved survival and treatment outcomes in comparison to other immunotherapy treated patients. 86,87 Compared with lower-GI toxicities, upper-GI toxicity is much less common and characterized by dysphagia, nausea or vomiting, and epigastric pain. 88,89 Patchy chronic duodenitis or chronic gastritis with rare granulomas may be identified on biopsies.…”