Efficacy of immunotherapy in MSI metastatic colorectal cancer patients: A Real-World Italian multicentric retrospective study (Colon-MSI Study).

Abstract

e15595 Background: The treatment with Immune checkpoint inhibitors (ICIs) is the gold standard therapy in metastatic colorectal cancer (mCRC) patients (pts) with microsatellite instability (MSI). The aim of the study was to describe a cohort of MSI mCRC pts treated with ICIs, before pembrolizumab approval, to evaluate efficacy and toxicity in a real-world setting and to identify possible predictive factors of response. Methods: We retrospectively collected data of pts with MSI mCRC treated with ICIs (anti-PD1 or anti-CTLA-4 antibodies, or in combination) before June 30, 2021, in 14 Italian Cancer Centers. The OS was calculated from the diagnosis of metastatic disease, and the PFS from the beginning of ICIs. Survival analyses were stratified between treatment naïve and pre-treated pts. We explored the correlation between clinicopathological factors and refractory pts who underwent progression disease (PD) within 3 months from the start of ICI. Results: In this preliminary analysis, we reported 60 consecutive pts with data available. Among all, 30 (50%) were male, 37 (62%) with ECOG PS 0-1; 21 (35%) were at stage IV, and 37 (62%) had right colon tumor site. The most common metastatic sites were lymph nodes, liver, and peritoneum, and 34 (57%) pts had a single metastatic site. 23 (38%) pts had a mucinous adenocarcinoma, and 20 (33%) were BRAF mutated. Nivolumab, Pembrolizumab, and Ipilimumab plus Nivolumab were administered in 24 (40%), 34 (57%), and 2 (3%) pts, respectively, and as first-line therapy in 13 (22%) pts. The median duration of treatment was 22 months (0-43), with 21 pts still ongoing. 13 (22%) pts were refractory to ICIs, and only 4 (7%) pts discontinued treatment for G3-G4 adverse events. The OS, PFS and DCR were different between treatment naïve and pre-treated pts with a positive trend (not statistically significant) toward untreated pts (Table 1). Male gender (p = 0.03), stage IV (p = 0.04), and ≥ 2 metastatic sites (p = 0.01) were significantly associated with refractory ICIs pts, but none of these factors was correlated with poor outcomes in multivariate analysis. Conclusions: Our preliminary data confirm that immunotherapy is an effective and well-tolerated treatment in MSI mCRC pts, with long-term clinical outcomes reported. These results suggest better outcomes when ICIs are administered in the first-line setting. Further analysis will be provided after the completion of the accrual. [Table: see text]