Results from the phase 3 FRESCO-2 trial support the approval of fruquintinib for patients with previously treated metastatic colorectal cancer.
Fruquintinib (Fruzaqla) has been approved by the FDA for patients with metastatic colorectal cancer (CRC) who have previously received fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy plus anti-VEGF therapy. It is also indicated for patients with RAS wild-type disease who were given an anti-EGFR therapy, according to a press release from the organization.1
The approval is based on results from the phase 3 FRESCO-2 trial (NCT04322539).2 Topline results from the trial included a median overall survival (OS) of 7.4 months (95% CI, 6.7-8.2) in the fruquintinib arm vs 4.8 months (95% CI, 4.0-5.8) in the placebo arm (HR, 0.66; 95% CI, 0.55-0.80; P <.0001).
“I think [fruquintinib] will be a standard of care for patients with metastatic [CRC]…Looking beyond just this approval, given that this drug has [impressive] efficacy and is well tolerated, there’s a lot of discussion and excitement around expanding its role into early lines of therapy and combining it with other agents, which has been challenging with regorafenib [Stivarga] so far,” lead study author Arvind N. Dasari, MD, associate professor in the Department of Gastrointestinal Medical Oncology in the Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center, said in an interview with CancerNetwork®.
A total of 691 patients were enrolled and randomly assigned 2:1 to receive either 5 mg of fruquintinib (n = 461) or matched placebo (n = 230) orally once daily on days 1 to 21 in a 28-day cycle plus best supportive care. Patients were stratified based on previous trifluridine–tipiracil (Lonsurf) or regorafenib treatment, RAS mutation status, and duration of metastatic disease.
The primary end point was OS. Key secondary end points included progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), duration of response (DOR), and safety.
The median patient age was 64 years, with 63% of patients having RAS mutations and 72% having liver metastases. The median lines of prior therapy were 4 for metastatic disease, and 73% of patients received more than 3 lines. Prior anti-VEGF therapy was given in 96% of patients, and 39% had prior anti-EGFR therapy.
In the fruquintinib arm, the median follow-up was 11.3 months vs 11.2 months in the placebo arm. The median PFS was 3.7 months (95% CI, 3.5-3.8) vs 1.8 months (95% CI, 1.8-1.9) in the fruquintinib and placebo arms, respectively (HR, 0.32; 95% CI, 0.27-0.39; P <.0001).
In the fruquintinib arm, the investigator-assessed ORR was 2% (95% CI, 0.6%-3.1%) vs 0% (95% CI, 0.0%-1.6%) in the placebo group (P = .059). The DCR in the fruquintinib group was 56% (95% CI, 50.9%-60.1%) vs 16% (95% CI, 11.6%-21.5%) with placebo (P <.0001). Additionally, the median DOR was 10.7 months (95% CI, 3.9-not estimable) in the fruquintinib arm.
At least 1 adverse effect (AE) occurred in 99% of patients in the fruquintinib group vs 93% in the placebo group. Grade 3 or higher AEs occurred in 63% in the fruquintinib group vs 50% in the placebo group, with the most common being hypertension (14% vs 1%), asthenia (8% vs 4%), and hand-foot syndrome (6% vs 0%). One treatment-related death was observed in the fruquintinib group from intestinal perforation, and 1 treatment-related death in the placebo group occurred due to cardiac arrest.
AEs leading to dose reductions occurred in 24% and 4% in both groups, respectively. Dose reductions mostly occurred in patients receiving fruquintinib due to hand-foot syndrome (5%), hypertension (4%), and asthenia (4%).
“For our patient population with surgically unresectable disease, we have limited treatment [options]… This just gives another opportunity to them, with good quality and improved OS. By improving the OS, it improves their own personal quality of life as well as their ability to potentially participate in another clinical trial,” Cathy Eng, MD, David H. Johnson Chair in Surgical and Medical Oncology, professor of medicine, coleader of the Gastrointestinal Cancer Research Program, codirector of gastrointestinal oncology, and director of the Young Adults Program at Vanderbilt-Ingram Cancer Center, said in an interview with CancerNetwork®.