To evaluate the efficacy and safety of the combination of immunotherapy and targeted therapy and chemotherapy in third-line treatment of patients with microsatellite stable (MSS) metastatic colorectal cancer (mCRC).

A retrospective cohort trial was conducted on patients with MSS mCRC treated with third-line immunotherapy combined with targeted therapy and chemotherapy in our hospital from January 2020 to December 2023. The clinical data were collected. Kaplan-Meier survival analysis was employed to analyze progression-free survival (PFS) and overall survival (OS). Objective response rate (ORR), disease control rate (DCR) and other indicators were statistically analyzed to evaluate the clinical efficacy. The incidence and severity of adverse events during the treatment process were recorded to assess the safety.

A total of 80 patients were included in the analysis, 55 in the group of immunotherapy plus targeted therapy and 25 in the group of immunotherapy combined with targeted therapy and chemotherapy. The group of immunotherapy combined with targeted therapy and chemotherapy had significantly longer median PFS (6.3 vs 4.4 months; HR=0.58, 95%CI: 0.35~0.96; P=0.031) and OS (15.5 vs 10.1 months; HR=0.47, 95%CI: 0.27~0.81; P=0.006), and obviously higher ORR (32.0% vs 10.9%; OR=0.26, 95%CI: 0.07~0.79; P=0.021) and DCR (92.0% vs 78.2%; OR=0.31, 95%CI: 0.07~1.52; P=0.132) when compared to the group of immunotherapy plus targeted therapy. The incidence of adverse events at all grade and at grade 3 and above was 96.4% and 32.7% in the group of immunotherapy plus targeted therapy, and 100.0% and 36.0% in the group of immunotherapy combined with targeted therapy and chemotherapy, which mainly included bone marrow hematopoietic inhibition, hand-foot skin reaction, liver function impairment and thyroid function abnormality.

The triple therapy of immunotherapy plus targeted therapy and chemotherapy is a more effective and safer treatment than the double therapy of immunotherapy plus targeted therapy in treatment of MSS mCRC patients.