The therapy is designed to target multiple receptors and could address an unmet need in metastatic colorectal cancer.
The days ahead of the 2023 American Society of Clinical Oncology Annual Meeting brought good news for patients with metastatic colorectal cancer (mCRC), as Takeda and HUTCHMED announced that FDA had granted priority review for their application for fruquintinib, the oral therapy already in use in China.1
Fruquintinib, a highly selective inhibitor of vascular endothelial growth factor receptors (VEGFR) -1, -2 and -3, works by blocking growth of blood vessels that feed tumor growth; its unique mechanism of action targets multiple receptors, and thus could improve survival in patients regardless of biomarker status.
Awny Farajallah, MD, head of Global Medical Affairs, Oncology, for Takeda, said approval of fruquintinib beyond China would fill a void in patient care.
“We really do not have good solutions for CRC—specifically for metastatic patients who continue to relapse from the disease, there is definitely an unmet need,” Farajallah said in an interview with Evidence-Based Oncology (EBO), noting that 70% of these patients do not have a mutation that can be treated with a targeted therapy.
Fruquintinib, he said, offers a combination of efficacy, safety, and targeting features that could help rising numbers of younger patients who will need treatments in mCRC. “We want to bring this to patients,” Farajallah said.
Besides being an oral drug, fruquintinib is designed to aid patients’ ability to stay on therapy by improving kinase selectivity, which limits off-target toxicities and increases tolerability. Fruquintinib was generally well-tolerated during clinical trials, and results presented during ASCO included phase IV data from China that showed the safety profile among 3000 real-world patients was consistent with clinical trial results.2
Those trials were, FRESCO (NCT02314819), conducted in China,3 and FRESCO-2 (NCT04322539), which involved 691 patients in the United States, Europe, Japan, and Australia, and investigated the use of fruquintinib plus basic supportive care (BSC) vs placebo plus BSC in patients with previously treated mCRC. Results for FRESCO-2, presented in September 2022 at the European Society of Medical Oncology (ESMO) and published June 15, 2023, in The Lancet, showed a 34% improvement in overall survival (OS) among the patients taking fruquintinib (HR 0.66; 95% CI, 0.55–0.80, P < .0001).4
In FRESCO-2, patients treated with fruquintinib achieved a median OS of 7.4 months vs 4.8 months with placebo; also, those treated with fruquintinib achieved a median progression-free survival of 3.7 months vs 1.8 months with placebo. The share of patients with adverse events of grade 3 or higher was 62.7% for the fruquintinib group vs 50.4% for the placebo group.
Cathy Eng, MD, who is the David H. Johnson Professor of Surgical and Medical Oncology and professor of Medicine at Vanderbilt University Medical Center and senior author of FRESCO-2, released a statement to coincide with publication of results in The Lancet.
“The majority of stage IV patients will have surgically unresectable disease. Hence, we must continue to pursue new treatment options to extend the overall survival of our patients with quality of life,” she said. “These findings from international FRESCO-2 validated the findings of the phase III FRESCO trial which was conducted only in China. Here we have a promising agent with overwhelming single agent activity.
“I look forward to the FDA approval as well as approvals from the European Medicines Agency and the Pharmaceuticals and Medical Devices Agency in Japan, so we can offer fruquintinib to all metastatic colorectal cancer patients.”5
Following the presentation at ESMO, Takeda and HUTCHMED announced the partnership in January 2023 to develop and market fruquintinib outside China.6 Thus, ASCO offered Takeda officials the opportunity to discuss both updated data and recent FDA activity, including a target action date of November 30, 2023, under the Prescription Drug User Fee Act.1 (On June 15, 2023, the European Medicines Agency also accepted the application for fruquintinib.7)
In the interview, Farajallah said there is an increased need for treatments such as fruquintinib, which can treat a broad spectrum of patients with mCRC. More patients are being diagnosed with the disease in their 40s, he said, as seen by the current US Preventive Services Task Force guidelines to screen for colon cancer starting at age 45.8,9
“So that tells you that we’re going to have more patients being diagnosed early, and unfortunately, more patients are going to progress and will require several lines of therapy,” he said.
Data on FRESCO-2 presented in 2022 at ESMO “caught our attention,” Farajallah said, “that this is a medicine that is effective not just in in the fact that it actually prolongs survival,” but also in the tolerability profile and the fact that it targets VEGF 1, 2, and 3.
“It’s very specifically targeting those mechanisms,” he said. “We think it lends itself to have better affordability. And we see that in the clinical trials, as well.”
The next step, Farajallah said, is identifying how fruquintinib can work in other cancers; indeed, an abstract presented at ASCO presented phase 2 data from a small trial (NCT04156958) where fruquintinib showed promise as a second-line or later treatment in biliary tract cancer.10
Other abstracts presented at ASCO included real-world data on the use fruquintinib with and without PD-1 inhibitors,11 and a subgroup analysis of FRESCO-2 based on prior lines of therapy.12
“I'm really eager to bring this medicine to patients,” Farajallah said. “Given the median overall survival that we're seeing, this is what really makes an impact for patients…. When I took care of patients, even 2 and a half months of survival for them was very meaningful. At a personal level, this is what gets you to see your son or your daughter graduate. if you're waiting for that; so it's very meaningful for patients.”