FRESCO-2: Fruquintinib improves OS in heavily pretreated mCRC

The FRESCO-2 study was positive and met its primary endpoint of achieving significantly longer OS in mCRC, said lead author Dr Arvind Dasari from the Department of Gastrointestinal Medical Oncology at the University of Texas MD Anderson Cancer Center in Houston, Texas, US.

During a median follow-up of 11 months, patients who received fruquintinib had a significantly longer median OS, with a 34-percent reduction in the risk of death than those who received placebo (7.4 vs 4.8 months; stratified hazard ratio [HR], 0.662; log-rank p<0.001). [ESMO 2022, abstract LBA25]

Patients on fruquintinib also achieved a significantly longer median progression-free survival than those on placebo (3.7 vs 1.8 months; stratified HR, 0.321; long-rank p<0.001).

The OS and PFS benefits were consistently observed with the fruquintinib arm vs the placebo arm across all prespecified subgroups, such as age and geographic region, and prior treatment exposure to VEGF and EGFR*** inhibitors, TAS-102 (trifluridine/tipiracil), and regorafenib.

A significantly higher disease control rate was observed among fruquintinib-treated patients compared with placebo-treated patients (55.5 percent vs 37.0 percent; p<0.001). Patients in the fruquintinib arm also showed a good objective response rate of 1.5 percent, which indicates that they achieved a tumour shrinkage even in a very refractory setting, Dasari noted.

Adverse events

Grade ≥3 treatment-emergent adverse events (TEAEs) occurred in 62.7 percent of patients on fruquintinib and 50.4 percent of patients on placebo.

Hypertension (13.6 percent), asthenia (7.7 percent), hand-foot syndrome (6.4 percent), and fatigue (3.9 percent) were the most frequent grade ≥3 TEAEs reported with fruquintinib, but these AEs have been commonly observed with other VEGF or VEGFR inhibitors. [JAMA 2018;319:2486-2496]

Previous and current FRESCO trials

Based on the results of the previous FRESCO⁺ trial, fruquintinib was approved in China in 2018 for patients with mCRC in the third-line setting and beyond. “However, the standard of care for mCRC in China differed from global patterns when FRESCO was conducted,” said Dasari.

Hence, the researchers conducted a global, phase III trial (FRESCO-2) involving 691 patients with refractory mCRC (mean age 64 years) who were recruited from the US, Europe, Japan, and Australia. Participants were randomized in a 2:1 ratio to receive either oral fruquintinib (5 mg) or placebo once daily (3 weeks on, 1 week off) in addition to best supportive care.

“The FRESCO-2 results are consistent with those of FRESCO and support [the use of fruquintinib as] a new global oral treatment option for patients with refractory mCRC, which enriches the continuum of care for these patients,” Dasari stated.

“Fruquintinib was also well tolerated with a safety profile consistent with the previously established monotherapy profile,” he added.

*VEGFR: Vascular endothelial growth factor receptor

**FRESCO-2: A study of efficacy and safety of fruquintinib (HMPL-013) in patients with metastatic colorectal cancer

***EGFR: Epidermal growth factor receptor