A real-world study of treatment patterns among patients (pts) with metastatic colorectal cancer (mCRC) receiving third-line (3L) or fourth-line (4L) treatment in the US.
Authors: Huichu Li, Scott Kopetz, Yu Yin, Jianling Peng, Hillary Keenan
Journal: Journal of Clinical Oncology (2025)

64 Background: There are limited real-world data describing 3L and 4L treatments for pts with mCRC. However, the landscape is evolving with new options becoming available, including fruquintinib, a highly selective oral inhibitor of all 3 VEGF receptors, approved by the US FDA in November 2023. This study aimed to understand pt characteristics and real-world treatment patterns in 3L and 4L to characterize the standard of care, adherence to guidelines, and identify unmet needs among pts with mCRC in the US, prior to recent changes in the landscape. Methods: A retrospective study of adults with mCRC who had received ≥3L of therapy between 1/1/2018 and 3/31/2023 in the US-based Flatiron electronic health records database. In two cohorts, defined by initiating 3L and 4L systemic treatment, pt demographics, clinical characteristics, and treatment by line of therapy were summarized. Results: Overall, 5401 pts were included in the 3L cohort and 2868 pts in the 4L cohort: median age at baseline was 63 and 62 years (yrs), 56% and 56% were male, 43% and 43% had a KRAS variant, and 46% and 49% had liver metastasis, respectively. 96% of pts in the 3L cohort received standard chemotherapy (CT) +/- targeted therapy as 1L treatment (55% CT + anti-vascular endothelial growth factor [VEGF] therapy; 34% CT only; 7% CT + anti-epidermal growth factor receptor [EGFR] therapy). In 2L, 87% of pts had standard CT-containing regimens (53% CT + anti-VEGF therapy; 19% CT alone; 15% CT + anti-EGFR therapy). A similar treatment history was observed for the 4L cohort. Commonly used 3L regimens in the 3L cohort were trifluridine/tipiracil (TAS-102; 11%), regorafenib (rego; 10%), and standard CT-containing regimens (54%; including: 12% FOLFIRI + bevacizumab [bev], 7% FOLFOX + bev, 4% FOLFIRI, 3% FOLFOX, and 15% standard CT + anti-EGFR therapy). Approximately 47% (n=2513) of pts did not receive subsequent treatments after 3L. In the 4L cohort, use of TAS-102 (16%) and rego (15%) increased slightly in 4L, accompanied with a moderate decrease in CT-containing regimens (42%; including 6% FOLFOX + bev, 5% FOLFIRI + bev, 3% FOLFOX, 3% FOLFIRI, and 12% standard CT + anti-EGFR therapy). Approximately 4% of pts in the 3L and 4L cohorts received TAS-102 + bev in 3L and 4L, respectively. Pts receiving standard CT-containing regimens were slightly younger (&lt;65 yrs: 3L 57%, 4L 58%) and had better Eastern Cooperative Oncology Group performance status (ECOG PS; 0-1: 3L 77%, 4L 77%) vs pts receiving TAS-102 (&lt;65 yrs: 3L 54%, 4L 58%; ECOG PS 0-1: 3L 70%, 4L 68%) or rego (&lt;65 yrs: 3L 50%, 4L 53%; ECOG PS 0-1: 3L 68%, 4L 70%). Conclusions: Characterization of treatment patterns in US pts from 1/2018 to 3/2023 showed that standard CT +/- targeted therapy was used frequently in 3L and 4L, demonstrating an unmet need for additional therapies. Approval of novel treatments, such as fruquintinib, may help to address this need.