The multi-TKI inhibitor regorafenib is standard-of-care in patients with (heavily) pre-treated, refractory mCRC1. The phase 3 FRESCO trial (NCT02314819) showed efficacy and safety of the VEGF-1, -2, and -3 inhibitor fruquintinib in Chinese patients with mCRC in a third (or later) line setting2. However, standard-of-care for mCRC in China differed from global patterns when FRESCO was conducted. For example, only 30% of participants in FRESCO had prior VEGF-inhibition and prior regorafenib was not allowed. To evaluate efficacy and safety of fruquintinib in a globally more representative population, FRESCO-2 (NCT04322539) was conducted in the USA, Europe, Japan, and Australia. Dr N. Arvind Dasari (MD Anderson Cancer Center, TX, USA) presented the first results3.
FRESCO-2 enrolled 691 patients with mCRC who had prior treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, who had anti-VEGF therapy and – if RAS wildtype – anti-EGFR therapy, who had progression on or intolerance to TAS-102 and regorafenib, and who had prior treatment with immune checkpoint inhibition or BRAF inhibition if indicated. About 72% of participants had 3 or more prior treatment lines for metastatic disease. Participants were 2:1 randomised to fruquintinib (5 mg once daily, 3 weeks on, 1 week of) or placebo until progression or unacceptable toxicity. All participants received best supportive care. The primary endpoint was OS, key secondary endpoint was PFS.
Fruquintinib significantly improved median OS compared with placebo (7.4 vs 4.8 months; HR 0.662; P<0.001). Fruquintinib favoured OS in all pre-specified subgroups. Of note, subsequent anti-cancer medication was balanced between the arms (29.4% in the fruquintinib arm and 34.3% in the placebo arm). PFS doubled in the fruquintinib arm (3.7 vs 1.8 months; HR 0.321; P<0.001). Objective response rate was 1.5% on fruquintinib versus 0% on placebo, whereas disease control rate was 55.5% versus 16.1%. Treatment-related adverse events grade ≥3 were observed in 36.0% of participants in the fruquintinib arm versus 11.3% of participants in the placebo arm.
“FRESCO-2 met its primary endpoint and the results are consistent with those of FRESCO, therefore supporting a new, global treatment option for patients with refractory mCRC,” concluded Dr Dasari.