Characteristics and Prognosis of Acquired Resistance to Immune Checkpoint Inhibitors in Gastrointestinal Cancer

Importance With the expanding use of immune checkpoint inhibitors (ICIs) in gastrointestinal (GI) cancer, the occurrence of acquired resistance (AR) has gradually emerged. However, the progression patterns and survival of patients with AR to ICIs are still unknown. Objective To explore the characteristics and prognosis of AR after ICI therapy in patients with advanced GI cancer. Design, Setting, and Participants This cohort study screened patients with advanced GI cancer treated with ICIs between January 14, 2016, and December 31, 2020, at Peking University Cancer Hospital. Initial response was defined as complete response, partial response, or stable disease longer than 6 months as assessed by Response Evaluation Criteria in Solid Tumors version 1.1. Progression was also based on Response Evaluation Criteria in Solid Tumors version 1.1. Progression or death after the initial response was defined as AR. Oligoprogression of AR was defined as 2 or more disease sites progression. The current status of AR in GI cancer and the patterns of AR and its prognosis were evaluated. The site of AR and subsequent management were also assessed. Data were analyzed from June to August 2021. Exposures Patients in the cohort were treated with mono-ICI or combination therapy. Main Outcomes and Measures Kaplan-Meier analyses and log-rank tests were conducted for overall survival analyses. Univariate and multivariate Cox analyses were conducted to determine the prognostic implications of each variable. Results Of the 1124 patients who received ICIs, 373 (33.2%) patients (282 men [75.6%]; median [IQR] age, 62 [54-68] years) achieved an initial response, and 173 (46.4%) patients (137 men [79.2%]; median [IQR] age, 61 [54-67] years) developed AR. Almost all patients (167 patients [96.5%]) developed AR within 24.0 months. Progression patterns of AR were most commonly oligoprogression (122 patients [70.5%]) rather than polymetastatic progression (38 patients [22.0%]) and were associated with a good prognosis (38.5 vs 14.0 months; hazard ratio, 0.37; 95% CI, 0.18-0.74; P < .001). Lymph nodes (101 patients [58.4%]) appeared to be the most common site of AR. Management after AR was mainly systemic therapy (96 patients [55.5%]). Conclusions and Relevance Oligoprogression was the most common pattern of AR progression, and lymph nodes were the most susceptible site for AR. Further study will be needed to determine the most favorable management for AR.