Fruquintinib plus best supportive care for patients with metastatic colorectal cancer: Characterization of patients who had an overall survival of ≥10 months in the FRESCO-2 study.
Authors: Kasper Stefan , Sartore-Bianchi Andrea , Randrian Violaine , Cremolini Chiara , Arnold Dirk , Dasari Arvind , Eng Cathy , Lonardi Sara , Elez Elena , Yoshino Takayuki , Sobrero Alberto F. , Yao James C. , Hochster Howard S. , Van Cutsem Eric , Tougeron David , Yu Ziji , Dong Cynthia , Schelman William R. , Ghiringhelli François 
Published: January 2025

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Background:
Fruquintinib (F) is a highly selective, oral tyrosine kinase inhibitor of all 3 vascular endothelial growth factor receptors (VEGFRs -1, -2, -3) that is approved by the US FDA and in the EU, UK, and Japan for previously treated metastatic colorectal cancer (mCRC), regardless of biomarker status. FRESCO-2 (NCT04322539) met its primary endpoint demonstrating significantly improved overall survival (OS) with F + best supportive care (BSC) vs placebo (P) + BSC. This subgroup analysis assessed landmark survival of all FRESCO-2 patients (pts), and baseline (BL) characteristics and safety data of pts treated with F who had OS ≥10 months (mos) compared with the intent-to-treat (ITT) population (pop).
Methods:
Pts were randomized 2:1 to receive F 5 mg or matching P, by mouth, once daily, 3 weeks on, 1 week off, + BSC. Pts had received prior chemotherapy, anti-VEGF therapy and, if
RAS
wild type, anti-EGFR therapy; and had prior exposure to trifluridine/tipiracil (TAS-102) and/or regorafenib. The hazard ratio (HR) between the two treatment arms was calculated from a stratified Cox proportional hazard model with treatment group as the only covariate in the model.
Results:
In the ITT pop, OS was improved with F vs P (HR 0.66); OS rates (95% confidence intervals [CIs]) at 6 and 9 mos were 60.4% (55.9–64.9) vs 41.5% (35.0–48.0) and 41.1% (36.4–45.8) vs 28.2% (22.1–34.3), respectively. Progression-free survival (PFS) rates (95% CIs) at 6 and 9 mos were 23.8% (19.7–28.0) vs 1.1% (0–2.6) and 11.3% (8.1–14.6) vs 0.5% (0–1.6), respectively. Of 461 pts who received F, 113 (24.5%) had OS ≥10 mos (range 10.0–18.9) with a median duration of F treatment of 6.3 mos (range 0.7–19.1). Among pts receiving F, a higher proportion (≥10% difference) of pts with OS ≥10 mos had no liver metastases (mets) and an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 at BL compared with the ITT pop (Table). In pts with OS ≥10 mos, 61.9% experienced a grade ≥3 treatment-emergent adverse event compared with 62.7% in the ITT pop.
Conclusions:
Longer-term OS and PFS rates at 6 and 9 mos were higher with F vs P in the FRESCO-2 ITT pop. The data show a higher proportion of pts with OS ≥10 mos had an absence of liver mets and ECOG PS 0 at BL than the ITT pop. The safety profile of F in pts with OS ≥10 mos was consistent with the ITT pop.
Clinical trial information: NCT04322539
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BL characteristics of pts treated with F with OS ≥10 mos vs ITT pop.

BL characteristic
Pts with OS ≥10 mos (n=113)
ITT pop(n=461)

ECOG PS (0 / 1), %
54.0 / 46.0
42.5 / 57.5

Median time since 1
st
CRC diagnosis, mos

52.0
47.2

Primary tumor location at 1
st
diagnosis (colon / rectum / both), %

51.3 / 35.4 / 13.3
60.5 / 31.0 / 8.5

Primary site at 1
st
diagnosis (colon left / colon right), %

42.5 / 15.9
41.6 / 21.0

Liver mets, %
58.4
73.5

Median duration of mCRC, mos
42.7
37.9

Prior lines of therapy for mCRC (≤3 / >3), %
26.5 / 73.5
27.1 / 72.9

Prior TAS-102, %
46.9
52.1

Prior regorafenib, %
12.4
8.7