Real-world evidence of fruquintinib (Fruq) efficacy after regorafenib (Rego) and trifluridine–tipiracil (TAS-102) in refractory metastatic colorectal cancer (mCRC).

Abstract

e23317 Background: mCRC poses significant challenges, particularly in patients (pts) who progress after multiple lines of therapy. Limited effective treatment options are available in the advanced chemotherapy-refractory setting. The FRESCO-2 trial demonstrated that Fruq, a selective VEGFR inhibitor, provides meaningful overall survival (OS) benefit in pts with refractory mCRC. However, there is limited real-world evidence regarding Fruq's efficacy in patients treated after approved third-line therapies. Methods: This retrospective, multi-site cohort study evaluated outcomes in 33 mCRC pts who received Fruq following treatment with Rego and/or TAS-102 with or without bevacizumab. Patients were stratified into two groups: Fruq as a second late-line therapy, after either Rego or TAS-102, (27 patients) and as a third late-line therapy, after both Rego and TAS-102, (6 patients). Overall survival (OS) was calculated from Fruq initiation to death, while time to treatment discontinuation (TTD) was defined as the duration from Fruq initiation to cessation for any reason, including death. Survival analysis was performed using the Kaplan-Meier method to estimate median survival, and the comparison between groups were done using the log-rank test. Results: Among the 33 pts, the median age was 58 years (range: 35–84), with 57.6% being male. Hepatic metastases were present in 78.8%, and 60.6% had left-sided primary tumors. RAS mutations were observed in 63.6%, and 97% were BRAF wild-type. Median OS was significantly longer in pts who received Fruq as a second late-line therapy (7.2 months) compared to those receiving it as a third late-line therapy (4.0 months) (p = 0.039). Median TTD was similar between groups (2.4 vs. 2.8 months, p = 0.916). Conclusions: This real-world analysis highlights the clinical benefit of Fruquintinib in mCRC patients following treatment with Regorafenib and/or TAS-102. The data suggest flexibility in treatment choices, with Fruquintinib showing improved OS when used earlier in the treatment sequence. These findings underscore the importance of exploring optimal sequencing strategies and evaluating Fruquintinib as a potential option before other approved agents in the refractory setting. Clinical outcomes with fruquintinib as second vs. third late-line therapy. Fruq as Second Late-Line Fruq as Third Late-Line p-value Median OS 7.2 months 4 months 0.039 Median TTD 2.4 months 2.8 months 0.916 OS: Overall Survival; TTD: Time to Treatment discontinuation.