On November 8, 2023, the FDA approved fruquintinib (Fruzaqla; Takeda Pharmaceuticals), an inhibitor of VEGFR-1, -2, and -3, for the treatment of metastatic colorectal cancer (mCRC) in adults who received previous fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, an anti-VEGF therapy, and, if RAS wild-type and medically appropriate, an anti-EGFR therapy. The FDA granted fruquintinib priority review for this indication.
The approval was based on efficacy results of 2 phase 3 clinical trials, FRESCO and FRESCO-2. The multicenter, placebo-controlled FRESCO trial was conducted in China and enrolled 416 patients with mCRC who had disease progression during or after receiving fluoropyrimidine-, oxaliplatin-, or irinotecan-based chemotherapy. In the multicenter, randomized, double-blind, placebo-controlled FRESCO-2 trial, 691 patients with mCRC were required to have disease progression during or after receiving trifluridine/tipiracil (Lonsurf; Taiho Oncology), or regorafenib (Stivarga; Bayer HealthCare Pharmaceuticals). They were also required to have received fluoropyrimidine-, oxaliplatin-, or irinotecan-based chemotherapy; an anti-VEGF biologic therapy; or, if RAS wild-type, an anti-VEGF therapy.
In both trials, patients were randomized to receive fruquintinib 5 mg orally once daily or placebo for the first 21 days of each 28-day cycle plus best supportive care. The patients received therapy until disease progression or until unacceptable adverse events.
The primary efficacy end point in both trials was overall survival (OS). In FRESCO-2, the median OS was 7.4 months (95% confidence interval [CI], 6.7-8.2) for patients receiving fruquintinib and 4.8 months (95% CI, 4.0-5.8) for patients receiving placebo (hazard ratio [HR], 0.66; 95% CI, 0.55-0.80; P<.001). In the FRESCO study, the median OS was 9.3 months (95% CI, 8.2-10.5) and 6.6 months (95% CI, 5.9-8.1) in the 2 treatment arms, respectively (HR, 0.65; 95% CI, 0.51-0.83; P<.001).
“Patients with metastatic [CRC] are often fragile and fatigued—due to both their condition as well as the therapies they have been exposed to. An oral chemotherapy-free option that offers a survival benefit despite treatment with prior therapies is a critical need for treating metastatic colorectal cancer,” stated Cathy Eng, MD, FACP, David H. Johnson Endowed Chair, Surgical and Medical Oncology, and Co-Leader, Gastrointestinal Cancer Research Program, Vanderbilt University Medical Center, Nashville, TN, in a press release. “Colorectal cancer is a highly heterogeneous disease, making it difficult to bring advancements to patients whose cancer has metastasized. I look forward to being able to offer a new solution to appropriate patients,” she added.
The most common (≥20%) adverse reactions with fruquintinib were hypertension, palmar-plantar erythrodysesthesia, proteinuria, dysphonia, abdominal pain, diarrhea, and asthenia.
The recommended dose of fruquintinib is 5 mg orally once daily with or without food for the first 21 days of each 28-day cycle until disease progression or unacceptable adverse reactions.
