Efficacy and safety of immune checkpoint inhibitors in heavily pretreated patients with microsatellite stable metastatic colorectal cancer: a real-world retrospective study.

Immune checkpoint inhibitor (ICI) has changed the situation of anti-tumor therapy. Several phase I/II clinical trials explored ICI-based combinations in microsatellite stable (MSS) metastatic colorectal cancer (mCRC) with mixed outcomes. However, real-world data regarding ICI-based combinations in this population is lacking. This retrospective study aimed to evaluate the efficacy and safety of ICI in MSS mCRC patients in third-line or above setting. A total of 143 eligible patients who received third-line or above ICI monotherapy or ICI-based combinations at the Cancer Center of Renmin Hospital of Wuhan University from June 2019 to April 2024 were included in this study. The primary endpoints were real-world median progression-free survival (PFS) and overall survival (OS), and the secondary endpoints included objective response rate (ORR), disease control rate (DCR), safety and prognostic analyses. Results showed that the median PFS was 4.6 months, and the median OS was 11.8 months, with an ORR of 11.2% and a DCR of 72.7%. ICI plus small molecule tyrosine kinase inhibitors have become the most popular combination for MSS mCRC patients at third-line or above setting with a median PFS of 4.4 months and OS of 10.1 months. The subgroup of patients with liver metastasis had worse clinical outcomes and liver metastasis was an independent prognostic factor for PFS (HR = 2.35, 95% CI, 1.54-3.59; P = 0.000) and OS (HR = 1.77, 95% CI, 1.06-2.96; P = 0.030). Forty-eight patients received cross-line ICI and obtained significantly improved OS (15.8 months vs 10.2 months; HR = 0.59, 95% CI, 0.38-0.89; P = 0.017). No new safety concerns were detected. Grade 3/4 treatment-related adverse events were generally controllable, with an incidence of 39.9%. To conclude, ICI-based combinations provide survival benefits for these heavily pretreated MSS mCRC patients with manageable safety, which is worthy of further study.