Immune checkpoint inhibitor in third-line treatment of microsatellite stable metastatic colorectal cancer: an observational and retrospective study

The third-line treatment options recommended by guidelines for metastatic colorectal cancer (mCRC) are limited with unsatisfactory efficacy. Immune checkpoint inhibitor (ICI)-based strategies have been extensively explored for microsatellite stable (MSS) mCRC at third-line and above settings. This study aimed to evaluate the efficacy and safety of ICI versus non-ICI-based treatments for MSS mCRC patients in third-line setting. Electronic medical records of MSS mCRC patients who received at least third-line therapies at Renmin Hospital of Wuhan University between September 2019 and April 2024 were reviewed retrospectively. Propensity score matching (PSM) was used to balance potential confounding factors. The primary outcomes of interest were progression-free survival (PFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR) and adverse events (TRAEs). Of 243 eligible patients, 93 received third-line ICI therapy and 150 treated with non-ICI therapy. The ORR were 12.9% vs 9.3% and DCR were 80.6% vs 72.0%, respectively. After PSM, an improved median PFS was exhibited in the ICI cohort (5.0 vs 3.6 months; HR = 0.55; 95% CI, 0.39–0.78; P < 0.001), with a directional improvement of OS (13.8 vs 12.4 months; HR = 0.70; 95% CI, 0.47–1.05; P = 0.086). In addition, a more significant survival benefit was found in the triplet regimen of ICI, chemotherapy and target therapy, with a median PFS of 8.2 months and OS of 20.2 months. Patients > 60 years of age, male, with liver metastasis, prior anti-VEGF(R) therapy, and wild-type RAS/BRAF could obtain PFS benefit from third-line ICI over non-ICI treatment. Thirty-six (38.7%) patients developed at least once cross-line immunotherapy in ICI cohort, resulting a directional OS improvement. Grade ≥ 3 AEs occurred in 39.8% and 43.3% of patients in each cohort. Immune-related AEs (irAEs) was 38.7%, and grade ≥ 3 irAEs was 14.0% in ICI cohort. ICI is a beneficial addition to third-line treatment for some MSS mCRC patients, providing improved survival benefit and controllable safety.