OBJECTIVES: Evidence suggests that patients with MSI-H or mismatch repair deficient (dMMR) mCRC have worse outcomes than those with MSS or mismatch repair proficient (pMMR) mCRC, but this mostly relates to first-line (1L) treatment. We compared time to next treatment or death (TTNTd) and overall survival (OS) in patients in the US with MSI-H/dMMR vs MSS/pMMR tumors on second-line (2L) and third-line (3L) non-immunotherapy standard of care mCRC treatment.

METHODS: Observational study using Flatiron Health electronic health record data on patients with mCRC diagnosed on/after 01/01/2013 who had received ≥1 line of prior therapy. Inverse probability (IP) weighting was used to control for baseline covariates (age, gender, race, disease stage at diagnosis, primary tumor location, KRAS/NRAS/BRAF status, insurance type, Eastern Cooperative Oncology Group score, treatment class). TTNTd and OS from start of 2L/3L therapy were analyzed using the IP-weighted Kaplan-Meier estimator. The association between MSI/MMR status and TTNTd/OS was evaluated using an IP-weighted Cox proportional hazards model with additional adjustment for covariates with a standardized mean difference of >0.10 after IP weighting to account for residual covariate imbalance.

RESULTS: For the IP-weighted 2L analysis, 110 patients had MSI-H and 2307 had MSS tumors; corresponding numbers for 3L were 50 and 1110. IP-weighted survival estimates were numerically shorter in MSI-H vs MSS tumors at both 2L (median TTNTd 6.24 vs 7.92 months; median OS 15.29 vs 17.09 months) and 3L (median TTNTd 5.29 vs 5.78 months; median OS 7.00 vs 11.47 months), but the differences were not statistically significant.