Real-world treatment patterns and outcomes in patients with mCRC by MMR/MSI status.
Authors: Victoria Crossland, Jianling Peng, Yu Yin, Yu-Chung Huang, Jeffrey Raizer, Alexander A Parent
Journal: Journal of Clinical Oncology (2024)

52 Background: There are limited data on real-world (RW) treatment patterns and outcomes in patients (pts) with metastatic colorectal cancer (mCRC), especially those with deficient mismatch repair (dMMR)/high microsatellite instability (MSI-H) disease, as they progress through lines of therapy. Methods: Data were extracted from the Flatiron Health electronic health record-derived database. Pts aged ≥18 years diagnosed with mCRC and with ≥2 clinical visits between January 01, 2013 and October 31, 2022 were included. Treatment patterns by therapeutic category and specific agent/regimens were explored across 3 time periods anchored to the start date of first line (1L): years &lt;2017, 2017–2019 and ≥2020 for pts both with dMMR/MSI-H and proficient mismatch repair (pMMR)/microsatellite stability (MSS) disease. Analyzed outcomes, by treatment category, included overall survival (OS), time to treatment discontinuation (TTD) and time to next treatment (TTNT). Descriptive statistics and Kaplan–Meier analyses were conducted. Results: A total of 34,853 pts with mCRC were identified; 24,622 pts (70.6%) were tested for MMR or MSI status, of whom 1,594 (6.5%) were dMMR or MSI-H. After applying key eligibility criteria, 938 dMMR/MSI-H and 12,305 pMMR/MSS pts were included. Overall, chemotherapy-based treatment was the most common treatment category given to pts, but the use of immuno-oncology (IO) agents increased over time. In the dMRR/MSI-H cohort, IO was the most commonly used treatment in 1L and 2L after 2020, driven largely by the use of pembrolizumab. The median OS (mOS) from start of 1L, irrespective of treatment type, was 30.30 months (95% confidence interval [CI]: 24.47, 34.41) in the dMMR/MSI-H cohort and 23.78 months (95% CI: 23.32, 24.34) in the pMMR/MSS cohort. For pts with dMMR/MSI-H, those receiving 1L IO had a mOS of 57.60 months (95% CI: 42.43, not reached [NR]). In pts who had IO after 1L-chemotherapy alone or chemotherapy + targeted treatment, mOS was 52.63 months (95% CI: 38.06, NR) and 59.61 months (95% CI: 34.41, NR), respectively. In pMMR/MSS pts, chemotherapy alone or chemotherapy + targeted treatment had the longest OS when received as 1L-therapy, at 23.88 months (95% CI: 22.89, 25.10) and 24.28 months (95% CI: 23.55, 25.10), respectively. The median TTD and TTNT from start date of 1L, irrespective of treatment type, were 4.90 months (95% CI: 4.28, 5.20) and 7.96 months (95% CI: 7.04, 8.78), respectively, in the dMRR/MSI-H cohort, and 5.79 months (95% CI: 5.72, 5.95) and 10.33 months (95% CI: 10.07, 10.59) in the pMMR/MSS cohort. Conclusions: These real-world data from over 10,000 pts with mCRC supplement findings from clinical trials and limited reported RW evidence. While IO demonstrates significant improvement for pts with dMMR/MSI-H, and mOS is similar regardless of whether IO is given in the 1L or later setting, there remains a high unmet need in pMMR/MSS for additional effective treatment options.