European Commission Approves Fruquintinib in Pretreated Metastatic CRC

"Given the complex nature of the disease, introducing innovative treatments such as fruquintinib—an oral, chemotherapy-free targeted agent—is essential," according to Josep Tabernero, MD, PhD.

The European Commission has approved fruquintinib (Fruzaqla) as a single-agent therapy for adults with previously treated metastatic colorectal cancer (CRC), according to a press release from the developers, Takeda.¹

Specifically, the agent is indicated for use in patients who received prior treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-containing chemotherapy, anti-VEGF agents, anti-EGFR therapy, and other standard treatments. Additionally, those with disease progression on or intolerance of trifluridine/tipiracil (TAS-102; Lonsurf) or regorafenib (Stivarga) are eligible for treatment with fruquintinib.

The European Medicine Agency’s Committee for Medicinal Products for Human Use expressed a positive opinion in support of approving fruquintinib for the aforementioned population in April 2024.² Supporting data for the approval came from the phase 3 FRESCO-2 trial (NCT04322539) assessing fruquintinib vs placebo in combination with best supportive care.

Findings previously published in The Lancet highlighted a median overall survival (OS) of 7.4 months (95% CI, 6.7-8.2) with fruquintinib vs 4.8 months (95% CI, 4.0-5.8) with placebo (HR, 0.66; 95% CI, 0.55-0.80; P <.0001).³ The 9-month OS rate was 41% (95% CI, 36%-46%) and 28% (95% CI, 22%-34%) in each respective arm.

The median progression-free survival (PFS) was 3.7 months (95% CI, 3.5-3.8) in patients who received fruquintinib compared with 1.8 months (95% CI, 1.8-1.9) among those who received placebo (HR, 0.32; 95% CI, 0.27-0.39; P <.0001). Additionally, subgroup analyses indicated that the OS and PFS benefits with fruquintinib extended to most prespecified subgroups, which included those who received prior trifluridine/tipiracil or regorafenib, those with RAS mutations, and those with varying lengths of metastatic disease.

Grade 3 or higher adverse effects (AEs) occurred in 63% of the fruquintinib arm compared with 50% of those in the placebo arm. Common high-grade AEs in each respective arm included hypertension (14% vs 1%), asthenia (8% vs 4%), and hand-foot syndrome (6% vs 0%).

“People living with metastatic [CRC have] numerous difficulties, stemming both from their illness and the [AEs] of therapies,” Josep Tabernero, MD, PhD, director of Vall d´Hebron Institute of Oncology, said in the press release.¹ “Given the complex nature of the disease, introducing innovative treatments such as fruquintinib—an oral, chemotherapy-free targeted agent—is essential. I am looking forward to having a new choice for appropriate patients.”

In the international, double-blind FRESCO-2 trial, patients were randomly assigned 2:1 to receive fruquintinib at 5 mg or matched placebo orally once daily on days 1 to 21 of 28-day cycles in combination with best supportive care.

The trial’s primary end point was OS, and PFS was a key secondary end point. Other secondary end points included objective response rate, disease control rate, duration of response, and safety.

Patients 18 years and older with histologically or cytologically confirmed metastatic colorectal adenocarcinoma and prior treatment with standard therapy were eligible for enrollment on the trial. Having an ECOG performance status of 0 or 1 and measurable disease per RECIST v1.1 criteria were additional requirements for study entry.

“Today's approval marks an important moment for the [CRC] community in the [European Union]. For the first time in over a decade, patients with previously treated metastatic [CRC] have a new targeted treatment option that can be used irrespective of whether their tumors harbor actionable mutations. We look forward to offering patients a novel treatment option that has a manageable safety profile and can be effective regardless of the prior types of therapies they have received,” Teresa Bitetti, president of the Global Oncology Business Unit at Takeda, concluded.¹

The FDA previously approved fruquintinib for patients with previously treated metastatic CRC in November 2023 based on findings from the FRESCO-2 trial.⁴

References

1. Takeda receives approval from European Commission for FRUZAQLA in previously treated metastatic colorectal cancer. News release. Takeda. June 21, 2024. Accessed June 24, 2024. https://tinyurl.com/ry49wm9r
2. Takeda receives positive CHMP opinion for fruquintinib in previously treated metastatic colorectal cancer. News release. Takeda. April 26, 2024. Accessed June 24, 2024. https://tinyurl.com/4ed4fac5
3. Dasari A, Lonardi S, Garcia-Carbonero R, et al. Fruquintinib versus placebo in patients with refractory metastatic colorectal cancer (FRESCO-2): an international, multicentre, randomised, double-blind, phase 3 study. Lancet. Published online June 15, 2023. doi:10.1016/S0140-6736(23)00772-9
4. Takeda receives U.S FDA approval of Fruzaqla (fruquintinib) for previously treated metastatic colorectal cancer. News release. Takeda. November 8, 2023. Accessed June 24, 2024. https://bit.ly/3SwkD8U