Immunotherapy-based treatment patterns and clinical outcomes across lines of therapy in microsatellite stable metastatic colorectal cancer: A real-world study.

Microsatellite stable (MSS) metastatic colorectal cancer (mCRC) hardly benefits from immune-monotherapy. Immune checkpoint inhibitor (ICI)-based combinations have been explored with mixed results. To evaluate the treatment patterns and outcomes across lines of immunotherapy in MSS mCRC, a retrospective real-world data analysis was performed in the present study. A total of 202 patients treated at Renmin Hospital of Wuhan University from June 2019 to December 2023 were included in the analysis, encompassing 38, 41 and 123 cases that received first-(1L), second-(2L) and third-line or above (3L+) ICI-based therapies, respectively. ICI combined with chemotherapy, ICI combined with chemotherapy and anti-VEGF(R)/EGFR/HER2 monoclonal antibody, and ICI combined with tyrosine kinase inhibitor (TKI) were the main options for the 1L, 2L and 3L+ cohorts, respectively. The objective response rates of the 1L, 2L and 3L+ treatment cohorts were 63.2, 22.0 and 11.4%, respectively, and the disease control rates of these three cohorts were 94.7, 75.6 and 70.7%, respectively. The median progression-free survival of the 1L, 2L and 3L+ cohorts was 11.1, 6.5 and 4.7 months, respectively, and overall survival (OS) was not reached, 16.0 and 11.9 months, respectively. After propensity score matching, patients who received ICI cross-line therapy at least once in the 3L+ cohort showed directional OS improvement (14.3 vs. 11.3 months; hazard ratio, 0.66; 95% confidence interval, 0.39-1.14; P=0.123) compared with those who did not receive ICI cross-line therapy. Grade ≥3 adverse events (AEs) occurred in 43.6% of patients, with thrombocytopenia, leukopenia and abnormal hepatic function being the most common. The incidence of immune-related AEs (irAEs) was 38.6% and that of grade ≥3 irAEs was 15.3%. These findings suggest that chemotherapy remains the cornerstone of 1L and 2L treatment for MSS mCRC, while the combination of ICI and TKI has developed into a major trend at the 3L+ setting with improved survival and controllable safety.