Abstract
BACKGROUND: Clinical trial evidence points to chemotherapy's potential in augmenting the effects of immunotherapy. AIM: To assess the effectiveness of first-line chemoimmunotherapy (CIT) for microsatellite stable (MSS) metastatic colorectal cancer (mCRC) verses standard-of-care (SOC; 5-fluorouracil/leucovorin/oxaliplatin/bevacizumab). METHODS: This was a multicenter retrospective cohort study conducted in Peking University First Hospital and Jilin Cancer Hospital. Patients with MSS mCRC who had received first-line treatment were eligible. The Kaplan-Meier method and Cox proportional hazard model were used to evaluate progression-free survival (PFS) and to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). PFS was set as the primary endpoint. Propensity score (PS) was calculated to balance the baseline characteristics of the two cohorts. With PS, we performed three statistical methods, namely inverse probability weighting, PS matching, and additional adjustment for PS with multivariate cox regression. RESULTS: Between July 2019 and November 2024, 148 eligible patients were enrolled, with 40 and 108 patients assigned to the CIT and SOC cohorts, respectively. At a global median follow-up of 21.4 months, the crude median PFS was 13.5 months (95%CI: 9.77-21.6) in the CIT cohort vs 9.1 months (95%CI: 7.8-10.6) in the SOC cohort, yielding a nonsignificant hazard ratio (HR) of 0.5645 (95%CI: 0.3637-0.8763, P = 0.01; SOC as reference). Multivariate Cox regression analysis, adjusted for sex, age > 60 years, Eastern Cooperative Oncology Group performance status, rat sarcoma mutation, primary tumor location (left vs right) and number of metastatic organs (liver/lung), demonstrated an adjusted HR of 0.55 (95%CI: 0.35-0.87, P = 0.011). PS-based analyses using PS matching (post-matching n = 40 vs 40), PS-adjusted multivariate Cox regression, and inverse probability weighting revealed consistent significant trends favoring CIT, with HRs for CIT of 0.5641 (95%CI: 0.3303-0.9635, P = 0.0361), 0.60 (95%CI: 0.38-0.96, P = 0.034), and 0.57 (95%CI: 0.337-0.973, P = 0.039), respectively. CONCLUSION: Efficacy of CIT in MSS mCRC could surpass that of standard first-line chemotherapy. Further research is needed to investigate specific clinical characteristics or biomarkers to identify patients who may derive benefit from CIT.