The combination of fruquintinib and best supportive care improved overall survival vs BSC alone in patients with metastatic colorectal cancer.
Fruquintinib (HMPL-013) in addition to best supportive care (BSC) demonstrated an improvement in overall survival (OS) compared with BSC alone in patients with metastatic colorectal cancer (mCRC), meeting the primary end point of the phase 3 FRESCO-2 trial (NCT04322539).1
Additionally, fruquintinib plus BSC resulted in a statistically significant improvement in progression-free survival (PFS) over BSC alone in this population which consisted of patients with mCRC who progressed on standard chemotherapy and relevant biologic agents, and who had progressed on or were intolerant to trifluridine/tipiracil (TAS-102; Lonsurf) and/or regorafenib (Stivarga). These data showed that a key secondary end point of the research was also met.
The highly selective, potent, oral inhibitor of VEGFR-1, VEGFR-2, and VEGFR-3 added to BSC proved to be consistent with what has been previously reported. According to HUTCHMED Limited, full findings from the trial will be submitted for presentation at a future medical conference.
“By meeting the primary end point of OS with a secondary end point of PFS, fruquintinib provides a significant potential new option for our refractory CRC patients,” said Cathy Eng, MD, FACP, FASCO, David H. Johnson Endowed Chair in Surgical and Medical Oncology, and co-leader of the Gastrointestinal Cancer Research Program at the Vanderbilt-Ingram Cancer Center, in the press release. “As an oral agent, fruquintinib also provides added convenience for our patients.”
In the global, randomized, double-blind, placebo-controlled, multicenter FRESCO-2 trial, 691 patients were enrolled to compare the safety and efficacy of fruquintinib plus BSC vs placebo plus BSC.2
Enrollment in the trial was open to patients aged 18 years and older who had histologically and/or cytologically documented mCRC with documented RAS, BRAF, microsatellite instability, or mismatch repair status. Other eligibility requirements included having an ECOG performance status of 0 or 1, an expected survival of longer than 12 weeks, a body weight of ≥40 kg, and measurable disease according to RECIST version 1.1.
Previously, the China National Medical Products Administration approved fruquintinib (Elunate) as a treatment option in patients with mCRC who previously received fluoropyrimidine, oxaliplatin, and irinotecan, as well as those who received prior anti-VEGF therapy and/or anti-EGFR therapy in September 2018 based on data from the phase 3 FRESCO trial (NCT02314819).3 Then in June 2020, the FDA granted a fast track designation to fruquintinib for this patient population.
Patients enrolled to FRESCO were between the ages of 18 years and 75 years, weighed at least 40 kg, and had histologically and/or cytologically confirmed mCRC that had progressed after at least 2 standard chemotherapy regimens.
To be eligible, patients were required to have disease progression during or within 3 months of their last standard treatment or have stopped treatment due to intolerable toxicity. They were also required to have an ECOG performance status of 0 or 1, left ventricular ejection fraction of at least 50%, measurable disease per RECIST V1.1 criteria, and acceptable bone marrow, liver, and renal function. Prior VEGF or EGFR inhibition was permitted.
There were 416 patients randomized to receive either fruquintinib (n = 278) or matching placebo (n = 138) plus BSC. Of those enrolled, the mean age of patients was 54.6 years with 38.7% female. The disease characteristics, baseline demographics, and prior treatments were similar between the experimental and control arms examined in the study. However, investigators noted there to be a higher proportion of male patients in the placebo group at 70.3% vs 56.8%, respectively.4
Patients were stratified based on prior VEGF inhibition (yes vs no) and KRAS mutational status (wild-type vs mutated). No crossover from the control arm to the investigative arm was permitted. Further, treatment was given until progressive disease, unacceptable toxicity, withdrawn content, discontinuation by physician, or death.
The primary end point of the trial was OS, with key secondary end points including PFS, objective response rate, and disease control rate. Other end points consisted of duration of response and safety.
Most patients had several metastases, with liver metastases present in 66.5% and 73.9% of those in the fruquintinib vs placebo arms. Additionally, in the fruquintinib arm, 30.2% of patients had previously received VEGF inhibitors vs 29.7% in the placebo arm. Then, 14.4% and 13.8%, respectively, had prior EGFR inhibitors, and 4.7% and 3.6%, had prior chemotherapy with VEGF and EGFR inhibitors. KRAS wild-type disease was observed in 56.5% of the investigative arm and 53.6% in the control arm.
Findingsrevealed fruquintinib to significantly prolong median OS over placebo, at 9.3 months (95% CI, 8.2-10.5) vs 6.6 months (95% CI, 5.9-8.1), respectively (HR, 0.65; 95% CI, 0.51-0.83; P < .001). A significantly prolonged median PFS was also seen with fruquintinib over placebo, at 3.7 months (95% CI, 3.7-4.6) and 1.8 months (95% CI, 1.8-1.8), respectively (HR, 0.26; 95% CI, 0.21-0.34; P < .001).
In regard to safety, treatment-emergent adverse events (AEs) either grade 3 or 4 in severity were observed in 61.2% of patients in the fruquintinib arm and 19.7% of those in the placebo arm. Serious AEs were reported in 15.5% and 5.8% of patients in the investigative and control arms, and 14.4% and 5.1% of patients required hospitalization.
“We are very happy to see the positive outcomes of the FRESCO-2 study which offers a potential new treatment for patients with advanced mCRC, where the unmet need is very high and patients have limited treatment options,” said Marek Kania, MD, MBA, executive vice president, managing director, and chief medical officer of HUTCHMED International, in a press release. “Results from the global FRESCO-2 study supplement findings from the original FRESCO study that led to the marketing approval and commercialization of fruquintinib in China.”