e15604 Background: As the landscape of mCRC treatment continues to evolve, it is important to understand real-world treatment patterns with newer agents. This study characterized current US treatment patterns for mCRC focusing on third line (3L) and fourth line (4L), including novel agents like fruquintinib (F) and trifluridine/tipiracil (TAS-102) combined with bevacizumab (TB). Methods: In this retrospective cohort study, patients ≥18 years of age at mCRC diagnosis who received ≥3 lines of treatment from January 1, 2015, to June 30, 2025, were identified using the nationwide de-identified Flatiron Health electronic health record derived database. The index date was defined as the 3L start date, and 3 months of follow-up (FU) from index was required unless the patient died. Treatments included regorafenib monotherapy (R), TAS-102 monotherapy (T), TB, F and other therapies. Overall 3L treatments by agent and most common regimens were described as well as the proportion of patients continuing to 4L. For 3L→4L sequential treatments with R→TB, R→F, TB→F, TB→R, sample size, baseline characteristics, time to treatment discontinuation (TTD), and number of subsequent lines were reported. All analyses were descriptive, and TTD was estimated by the Kaplan–Meier method. Results: Out of a total of 46,033 mCRC patients, 6,640 received ≥3 lines of treatment during the study period. Median age was 61 years, 58% were male, 64% had Stage IV at initial diagnosis, 72% had ECOG PS 0 or 1 at index date, and 89% were treated in community practice. Median FU was 9.0 months (IQR 4.6, 17.3). Of the patients treated in the 3L setting, 29% received R, T, TB, and F, and 71% received other therapies (Table). A total of 3,377 (50.9%) went on to receive 4L treatments. Median TTD of sequential treatments with R, TB, and F ranged from 7.4 to 12.9 months. Conclusions: In this real-world cohort from predominantly community oncology practices in the US, R, T, TB, and F accounted for approximately 29% of 3L treatments. Use of newer agents indicated heterogeneous adoption in current clinical practice. Patients treated in 3L N= 6,640. Regorafenib monotherapy 720 10.8% TAS-102 monotherapy 717 10.8% TAS-102, bevacizumab 403 6.1% Fruquintinib monotherapy 79 1.2% Other therapies* 4,721 71.1% FOLFIRI + bevacizumab; FOLFIRI; FOLFIRI + panitumumab 1,302 19.6% FOLFOX + bevacizumab 487 7.3% Irinotecan + cetuximab 213 3.2% *Therapies listed below are the most common other therapies for patients treated in 3L.
Pan et al. (2026) studied this question.