Findings from the phase 3 FRESCO-2 trial support fruquintinib plus best supportive care as a global treatment option for patients with refractory metastatic colorectal cancer.
Combining fruquintinib (HMPL-103) with best supportive care produced a statistically significant and clinically meaningful improvement in overall survival (OS) compared with placebo in the treatment of patients with refractory metastatic colorectal cancer (CRC), according to findings from the phase 3 FRESCO-2 trial (NCT04322539) published in The Lancet.1
With a median follow-up of 11.3 months (interquartile range [IQR], 9.0-14.2) in the fruquintinib group and 11.2 months (IQR, 8.7-15.5) in the placebo group, the median OS was 7.4 months (95% CI, 6.7-8.2) vs 4.8 months (95% CI, 4.0-5.8) in each respective group (Hazard ratio [HR], 0.66; 95% CI, 0.55–0.80; P <.0001). At 9 months, 41% (95% CI, 36%-46%) of patients receiving fruquintinib were alive compared with 28% (95% CI, 22%-34%) of those in the placebo group. Additionally, the median progression-free survival (PFS) was 3.7 months (95% CI, 3.5-3.8) vs 1.8 months (95% CI, 1.8-1.9) in each respective group (HR, 0.32; 95% CI, 0.27-0.39; P <.0001).
In an analysis of patient subgroups—in which patients were stratified based on previous treatment with trifluridine/tipiracil (Lonsurf) or regorafenib (Stivarga), RAS mutation status, and duration of metastatic disease—investigators reported that OS and PFS benefits with the fruquintinib regimen were comparable with those observed in the intent-to-treat population.
“Patients with refractory metastatic [CRC] have very limited treatment possibilities and poor outcomes,” lead investigator Arvind Dasari, MD, associate professor of Gastrointestinal Medical Oncology at The University of Texas MD Anderson Cancer Center, said in a press release on these data.2 “These results are very encouraging and confirm that fruquintinib may be a novel treatment opportunity for patients who previously had no other options.”
Investigators of the international, double-blind, randomized phase 3 FRESCO-2 trial assessed patients at 124 hospitals and cancer centers across 14 countries in North America, Asia, Europe, and Australia. A total of 691 patients were randomly assigned 2:1 to receive 5 mg of fruquintinib (n = 461) or matched placebo (n = 230) orally once a day on days 1 to 21 of each 28-day cycle in combination with best supportive care.
The primary end point was OS, and PFS was a key secondary end point. Other secondary end points included objective response rate (ORR), disease control rate (DCR), duration of response (DOR), and safety.
Patients 18 years and older with a histologically or cytologically confirmed diagnosis of metastatic colorectal adenocarcinoma were eligible for enrollment on the trial. Receiving standard treatment options including fluoropyrimidine, oxaliplatin, and irinotecan chemotherapy and having disease progression following treatment with trifluridine/tipiracil or regorafenib were also requirements to enroll.
The median age was 64 years (IQR, 56-70) in the overall population. Additionally, 63% of patients had a RAS-mutated tumor, and 72% had liver metastases. Patients received a median of 4 (IQR, 3-6) prior lines of therapy for metastatic disease, and 73% received more than 3 prior lines. Additionally, 96% and 39% of patients received prior anti-VEGF therapy and anti-EGFR therapy, respectively.
Investigators indicated that baseline disease characteristics and demographics were generally comparable between the fruquintinib and placebo treatment groups.
The investigator-assessed ORR was 2% (95% CI, 0.6%-3.1%) in the fruquintinib group vs 0% (95% CI, 0%-1.6%) in the placebo group (P = .059). Additionally, the DCR was 56% (95% CI, 50.9%-60.1%) vs 16% (95% CI, 11.6%-21.5%) in each group (P <.0001). The median DOR for patients receiving fruquintinib was 10.7 months (95% CI, 3.9-not estimable), and the maximum DOR ranged from 2.1 to 16.9 months.
At least 1 adverse effect (AE) occurred in 99% of patients in the fruquintinib group and 93% of those in placebo group. The most common any-grade AEs in each group included hypertension (37% vs 9%) and asthenia (34% vs 23%). Grade 3 or higher AEs affected 63% and 50% of patients in each group, the most common of which included hypertension (14% vs 1%), asthenia (8% vs 4%), and hand-foot syndrome (6% vs 0%). There was 1 treatment-related death in the fruquintinib group due to intestinal perforation and 1 treatment-related death in the placebo group due to cardiac arrest.
Overall, 24% and 4% of patients in the fruquintinib and placebo groups, respectively, experienced AEs leading to dose reductions. Patients receiving fruquintinib most frequently had dose reductions due to hand-foot syndrome (5%), hypertension (4%), and asthenia (4%).