OS End Point Met in Phase 3 FRESCO-2 Trial Examining Fruquintinib in Metastatic CRC


Overall survival, the primary end point of the phase 3 FRESCO-2 trial, was met when patients were given fruquintinib vs placebo for advanced refractory metastatic colorectal cancer.

The phase 3 FRESCO-2 trial (NCT04322539) met its primary end point of overall survival (OS) with fruquintinib for patients with advanced refractory metastatic colorectal cancer (CRC) vs matched placebo, according to a press release from Hutchmed Limited.1

Patients who had progressed on prior chemotherapy and relevant biologic agents as well as had progressive disease with TAS-102 and/or regorafenib (Stivarga) were treated with fruquintinib or placebo, both plus best supportive care. A key secondary end point was progression-free survival (PFS), which was also statistically significantly improved with fruquintinib plus placebo. The safety profile remained consistent with previously reported studies.

“We are very happy to see the positive outcomes of the FRESCO-2 study which offers a potential new treatment for patients with advanced metastatic colorectal cancer, where the unmet need is very high and patients have limited treatment options,” Marek Kania, MD, MBA, executive vice president, managing director, and chief medical officer of HUTCHMED International, said in the press release.

The global, randomized, double-blind, placebo-controlled multicenter trial enrolled 691 patients with advanced refractory metastatic colorectal cancer. Patients were eligible for treatment if they had histologically or cytologically documented metastatic colorectal adenocarcinoma and were previously treated with immune checkpoint inhibitors if their disease was microsatellite instability high or mismatch-repair deficient. Patients must have an ECOG score of 0 or 1, measurable disease, and expected survival of 12 weeks or more.

Ineligibility for treatment was defined as having an absolute neutrophil count of less than 1.5 × 109/L, a platelet count of less than 100 × 109/L, or hemoglobin of less than 9.0 g/dL. Patients must not have a serum total bilirubin of more than 1.5 times the upper normal limit, alanine or aspartate aminotransferase of more than 2.5 times the upper normal limit, or serum creatine of 1.5 times or more of the upper limit or less than 60 mL per minute. Patients must not have uncontrolled hypertension, an International Normalized Ratio of 1.5 times or more than the upper limit, or a history of gastric or duodenal ulcer or ulcerative colitis.

Fruquintinib was previously approved in China in September 2018 for patients with metastatic CRC who have previously been treated with fluoropyrimidine, oxaliplatin, and irinotecan, including those who have previously received anti-VEGF therapy and/or anti-EGFR therapy.

The approval was based on the phase 3 FRESCO trial conducted in China that enrolled 416 patients with CRC who were receiving treatment in the third-line setting or later.2 Randomization was done by a 2:1 ratio, with patients receiving either 5 mg of fruquintinib or placebo orally for 21 days on, 7 days off until disease progression, intolerable toxicity, or study withdrawal. The median OS was 9.3 months (95% CI, 8.2-10.5) in the fruquintinib arm and 6.6 months (95% CI, 5.9-8.1) in the placebo arm (HR, 0.65; 95% CI, 0.51-0.83; P <.001). The median PFS was 3.7 months (95% CI, 3.7-4.6) in the fruquintinib arm and 1.8 months (95% CI, 1.8-1.8) in the placebo arm (HR, 0.26; 95% CI, 0.21-0.34; P <.001).

Adverse effects (AEs) of grade 3/4 occurred in 61.2% of patients in the fruquintinib arm and 19.7% in the placebo arm, with serious AEs occurring in 15.5% vs 5.1%, respectively. In the fruquintinib arm, 14.4% of patients required hospitalization compared with 5.1% in the placebo arm.

In June 2020, the FDA granted fast track designation to fruquintinib for the treatment of patients with CRC with prior experience with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, a VEGF inhibitor, and, in the presence of RAS wild-type disease, an EGFR inhibitor.3 Further results of the FRESCO-2 study will be presented at an upcoming meeting.


  1. HUTCHMED announces that fruquintinib global phase 3 FRESCO-2 study has met its primary end point in metastatic colorectal cancer. News Release. HUTCHMED. August 7, 2022. Accessed August 9, 2022. https://yhoo.it/3bHIhMA
  2. Li J, Qin S, Xu RH, et al. Effect of Fruquintinib vs placebo on overall survival in patients with previously treated metastatic colorectal cancer: the FRESCO randomized clinical trial. JAMA. 2018;319(24):2486-2496. doi:10.1001/jama.2018.7855
  3. Chi-Med announces fruquintinib granted U.S. FDA fast track designation for metastatic colorectal cancer. News Release. HUTCHMED. June 18, 2020. Accessed August 9, 2022. https://bit.ly/3QszsFl

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