Fruquintinib: a potential new treatment for patients with refractory mCRC

Results from the phase 3 FRESCO-2 trial demonstrated a doubling of progression-free survival (PFS) and almost doubling of overall survival (OS) with VEGF-1, -2, and -3 inhibitor fruquintinib versus placebo in patients with refractory metastatic colorectal cancer (mCRC).

The multi-TKI inhibitor regorafenib is standard-of-care in patients with (heavily) pre-treated, refractory mCRC [1]. The original phase 3 FRESCO trial (NCT02314819) showed efficacy and safety of the VEGF-1, -2, and -3 inhibitor fruquintinib in Chinese patients with mCRC in the third (or later) line setting [2]. However, standard-of-care for mCRC in China differed from global patterns when the original FRESCO trial was conducted (e.g. only 30% of participants had prior VEGF inhibition). To evaluate the efficacy and safety of fruquintinib in a globally more representative population, FRESCO-2 (NCT04322539) was conducted in the USA, Europe, Japan, and Australia. Prof. Nageshwara Arvind Dasari (MD Anderson Cancer Centre, TX, USA) presented the first results [3].

FRESCO-2 enrolled 691 patients with mCRC who had prior fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, anti-VEGF therapy and –if RAS wildtype– anti-EGFR therapy. All participants had progressed in disease stage or were intolerant to TAS-102 and regorafenib, and had prior treatment with immune checkpoint inhibition or BRAF inhibition if indicated. 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 off) or placebo until progression or unacceptable toxicity. All participants received the best supportive care. The primary endpoint was OS and the 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). The objective response rate was 1.5% for participants receiving fruquintinib versus 0% for placebo, whereas the disease control rate was 55.5% versus 16.1%. Grade ≥3 treatment-related adverse events (mainly hypertension and asthenia) were observed in 36% of participants in the fruquintinib arm versus 11.3% of participants in the placebo arm.

“The FRESCO-2 trial met its primary endpoint and the results are consistent with those of the FRESCO trial, supporting fruquintinib as a new, global treatment option for patients with refractory mCRC,” concluded Prof. Dasari.

1. Van Cutsem E, et al. Ann Oncol. 2014; 25:(Suppl 3):iii1–iii9.
2. Li J, et al. JAMA 2018; 319(24):2486–2496.
3. Dasari NA, et al. FRESCO-2: A global phase III multiregional clinical trial (MRCT) evaluating the efficacy and safety of fruquintinib in patients with refractory metastatic colorectal cancer. Abstract LBA25, ESMO Congress 2022, 09–13 September, Paris, France.

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Posted on 16 November, 202228 March, 2024