MSI-H colon cancer: Can we utilize a watch and wait approach?

Abstract

e15652 Background: Recent studies shown that neoadjuvant Immune checkpoint inhibitor (ICI) followed by watch and wait (WW) with salvage surgery at recurrence is a safe strategy in patients (pts) with microsatellite instability-high (MSI-H)/deficient Mismatch repair (dMMR) rectal cancer (NICHE), and esophageal cancer (NEONIPIGIA). However, limited data are available for pts with MSI-H/dMMR colon cancer (CC). Methods: In this retrospective study, we searched TriNetX data for pts with MSI-H/dMMR CC received neoadjuvant ICI (pembrolizumab (pembro), nivolumab+ipilimumab (nivo+ipi), or dostarlimab) without surgery (cohort 1 = C1) and compared them to pts with upfront surgery (cohort 2 = C2). Primary outcome was overall survival. Secondary outcomes were rate of infection, rate of metastatic disease (mets), and immune related adverse events (irAE) in C1. Analysis methods included measures of association, number of instances, and Kaplan-Meier survival estimates. Results: Follow up was at least 5 years in both cohorts. Pts in C1 received ICI (mean in days) for 668 nivo+ipi (11 pts); 754 pembro (33 pts). Age (mean in years) in C1 was 66 and 67 in C2. Pts were predominantly caucasian (C1 77%, C2 62%); and female (C1 51%; and 52% C2). Follow up (mean in days) for C1 661; and 728 in C2. Stage II disease was 50% in C1; 46% in C2. Mean CEA level (ng/mL) 50 in C1; and 6 in C2. For C1, survival probability was statically lower; with higher rate of mets (commonly liver in both groups, about 26%). After propensity score-matching (PSM), survival was trending in favor of surgery (C2); with higher mets in C1. No difference in rate of infection. All irAE in C1 was < 10% (predominantly thyroid). Conclusions: Based on this data it appears that ICI without surgery in local MSI-H CC is inferior to upfront surgery. The data are discordant from other trials with MSI-H disease. The study limitations include retrospective design, lack of access to pts original medical record, rationale for upfront ICI instead of surgery, and small sample size. Further studies are needed to assess the efficacy of upfront ICI followed by WW approach. Summary of outcomes. Before PSM After PSM Cohort 1 Cohort 2 P value 95% CI (HR) Cohort 1 Cohort 2 P value 95% CI (HR) Total # of pts 44 95 - - 40 40 - - Overall survival probability 62% 82% 0.019* 1.13-5.13 (2.409)* 65% 84% 0.06 0.92-7.48(2.6) Rate of mets 61% (27/44) 25% (24/95) 0.005* - 55% (22/40) 33% (13/40) 0.035* - Rate of infection 46% 36% 0.24 - 40% 33% 0.52 - *=statistically significant.