Dr Hochster on the FRESCO-2 Trial in mCRC

Howard S. Hochster, MD, distinguished professor of medicine, associate director, Clinical Research, director, Gastrointestinal Oncology, Rutgers Cancer Institute, director, Oncology Research, RWJ Barnabas Health, discusses data from the phase 3 FRESCO-2 trial (NCT04322539) of fruquintinib (HMPL-013) plus best supportive care (BSC) in metastatic colorectal cancer (mCRC).

In May of 2023, the FDA granted priority review to the new drug application for the highly selective and potent oral VEGF-targeted agent based on findings from the FRESCO-2 study. The FRESCO-2 trial, which was conducted in the United States, confirmed findings from the phase 3 FRESCO trial (NCT02314819), which was conducted in China. In the FRESCO trial, the agent was shown to be an effective treatment alternative for patients in the third line or later line, following standard chemotherapy and targeted therapy.

FRESCO-2 enrolled patients with mCRC who were previously exposed to chemotherapy with fluoropyrimidine, oxaliplatin, or irinotecan; a VEGF inhibitor; or an EGFR inhibitor, provided they had RAS wild-type disease. The trial was double-blinded, except for instances in which patients developed uncontrollable hypertension. This rigorous methodology reinforces the credibility of the results. Notably, most patients on the trial who responded to the fruquintinib combination had been previously treated with regorafenib (Stivarga) or trifluridine/tipiracil (TAS-102; Lonsurf).

Results from the FRESCO-2 study showed that fruquintinib plus best supportive care produced superior overall survival (OS) and progression-free survival (PFS)benefit vs placebo and best supportive care. The median OS in the fruquintinib arm was 7.4 months (95% CI, 6.7-8.2 compared with 4.8 months (95% CI, 4.0-5.8) in the placebo arm (n = 230; HR, 0.662; 95% CI, 0.549-0.800; P < .001).

Data from subgroup analyses of the phase 3 FRESCO-2 trial(NCT04322539) revealed that improved OS was observed regardless of the number of prior lines of therapy patients received or the type of prior treatment administered. Heavily pretreated patients with prior exposure to more than 4 prior lines of therapy experienced a median OS of 7.1 months (95% CI, 6.3-8.5) with fruquintinib (n = 214) vs 4.6 months (95% CI, 3.4-5.9) with placebo (n = 107; HR, 0.595; 95% CI, 0.453-0.781; P < .001). The agent was deemed tolerable, and its safety profile is consistent with previously reported data.

Positive outcomes from the FRESCO-2 trial have the potential to support any future FDA approval of fruquintinib in mCRC, Hochster says. The regulatory decision is anticipated to be made by November, 2023, and it is expected that an Oncologic Drugs Advisory Committee (ODAC) meeting will not be necessary, he notes. This suggests that patients may have access to this promising therapy in the near future. If approved, fruquintinib could provide patients who have exhausted other eligible therapies with another effective treatment option, Hochster concludes.