In a phase III clinical trial, fruquintinib achieved improved overall survival (OS) in refractory metastatic colon cancer (mCRC) compared to best supportive care (BSC) alone, according to a randomised trial reported at the European Society for Medical Oncology (ESMO) annual congress.
BSC plus fruquintinib improved median OS to 7.4 months compared to 4.8 months with BSC plus placebo.
Patients with mCRC have few treatment options and a poor prognosis. Regorafenib is currently the only tyrosine kinase inhibitor (TKI) with an indication for mCRC.
The heavily treated patient population had received a median of five prior therapies, including regorafenib in about half of cases, N. Arvind Dasari, MD, of the University of Texas MD Anderson Cancer Center in Houston, presenting the results.
“These results are both clinically and statistically significant and consistent across all prespecified subgroups,” said Dr Dasari. “Fruquintinib was also well tolerated and consistent with a prior established safety profile. Overall, these results are consistent with [a prior trial conducted in China] and support a new practice-changing global oral treatment option for patients with metastatic colorectal cancer, enriching the treatment continuum for these patients.”
Dr Dasari noted that the VEGF pathway is a key mediator of angiogenesis, and fruquintinib is a selective and potent inhibitor of VEGF receptors 1, 2, and 3. In the phase III FRESCO trial conducted in China, fruquintinib resulted in statistically significant improvement in OS and progression-free survival (PFS), and received an approved indication for mCRC in fourth line and beyond.
Dr Dasari reported findings from the FRESCO-2 trial, which was designed to evaluate fruquintinib in a more diverse, multiregional patient population. Investigators enrolled patients with mCRC and a treatment history that included chemotherapy, anti-VEGF therapy, and anti-EGFR therapy. Patients with progression or intolerance to TAS-102, and regorafenib were eligible, as well as patients previously treated with an immune checkpoint inhibitor or a BRAF inhibitor.
Patients randomised 2:1 to BSC plus either fruquintinib or placebo. Treatment continued until disease progression or development of unacceptable toxicity.
The primary endpoint was OS, and the principal statistical assumption was that the control arm would have a median OS of 5.0 months, which would be improved to 6.8 months with fruquintinib.
The trial had 691 patients with a median follow-up of 11.2 months. Almost all of the patients had prior exposure to a VEGF inhibitor, about 40% had received an EGFR inhibitor, about 60% had received TAS-102 or regorafenib, and about 40% had received both. Dr Dasari said the patient population resembled the patients that clinicians see in clinical practice.
The primary analysis showed a 2.6-month improvement in median OS with fruquintinib, which translated into a survival hazard of 0.662.
Treatment with fruquintinib more than doubled the median PFS, from 1.8 months with placebo to 3.7 months, a 68% reduction in the hazard ratio. Seven patients in the fruquintinib arm had objective responses versus none in the placebo arm. The clinical benefit rate (response plus stable disease) was 55.5% with fruquintinib and 16.1% with placebo.
Grade ≥3 treatment-related adverse events occurred in 36.0% of the treatment arm and 11.3% of the placebo arm.
FRESCO-2 was not designed as a head-to-head comparison with regorafenib and was instead designed to validate fruquintinib for mCRC, said ESMO invited discussant Filippo Pietrantonio, MD, of the National Cancer Institute in Milan, Italy. The primary endpoint would have been noninferiority or equivalence. Even so, the trial set a high bar, as almost half the patients were 65 or older, had received multiple prior lines of therapy, and there were limitations on the proportion of patients with prior regorafenib treatment.
“Despite the challenges, FRESCO-2 is a positive trial, so fruquintinib may be a new standard-of-care option in patients with refractory metastatic colorectal cancer,” said Dr Pietrantonio. “This agent significantly prolonged overall survival and progression-free survival independently from prior treatment.”
“Sustained inhibition of angiogenesis is still important in later treatment lines, and fruquintinib provided an additional incremental gain of survival,” he added. “Real world and phase IV data are necessary to further assess the safety of fruquintinib, especially in underrepresented populations, and quality-of-life data are necessary as well.”
Source: MedPage Today
