Fruquintinib can reduce the risk of death by 34% on advanced colorectal cancer

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Fruquintinib can reduce the risk of death by 34% on advanced colorectal cancer

Fruquintinib can reduce the risk of death by 34% on advanced colorectal cancer.

“The Lancet” Heavy papper: Fruquintinib reaches the top again! Global study confirms that third-line treatment of advanced colorectal cancer with fruquintinib can reduce the risk of death by 34%

Effective systemic treatment options are lacking for patients with advanced chemotherapy-refractory colorectal cancer.

We aimed to evaluate the efficacy of fruquintinib, a highly selective and potent oral inhibitor of vascular endothelial growth factor receptors (VEGFRs) 1, 2, and 3, in heavily pretreated patients with metastatic colorectal cancer. sex and safety.

Recently, a blockbuster clinical study entitled “Fruquintinib versus placebo in patients with refractory metastatic colorectal cancer (FRESCO-2): an international, multicentre, randomised, double-blind, phase 3 study” published in “The Lancet” FRESCO- 2 The results showed that the small-molecule anti-angiogenic targeted drug fruquintinib was successful again in the treatment of chemotherapy-refractory advanced colorectal cancer (CRC), which could reduce the risk of death by 34% (HR=0.66) .

https://doi.org/10.1016/S0140-6736 (23) 00772-9

Research Background

Colorectal cancer is the third most diagnosed cancer and the second leading cause of cancer-related death worldwide. Approximately 50% of colorectal cancer patients develop distant metastases during the course of the disease; the 5-year overall survival rate for such patients is 15%.

Standard initial systemic therapy for metastatic colorectal cancer includes chemotherapy and targeted therapy as appropriate, with later non-selective treatment options including the oral agents trifluridine-tipiracil and regorafenib (a multikinase inhibitors), which have been shown to have an effect on the increase in median overall survival.

Therefore, there is an unmet need for safe and effective treatments for patients with refractory metastatic colorectal cancer.

Fruquintinib is a highly selective and effective oral tyrosine kinase inhibitor that targets vascular endothelial growth factor receptors (VEGFRs), which are key regulatory factors associated with tumor growth and metastasis. In the phase 3 FRESCO study (NCT02314819), fruquintinib treatment demonstrated significant efficacy compared to placebo in patients with metastatic colorectal cancer who had received at least two lines of chemotherapy.

The results showed improved overall survival (median 9.3 months [95% CI 8.2-10.5] vs. 6.6 months [5.9-8.1]; hazard ratio [HR] 0.65 [95% CI 0.51-0.83]; p<0.001) and progression-free survival (median 3.7 months [3.7-4.6] vs. 1.8 months [1.8-1.8]; HR 0.26 [0.21-0.34]). These findings led to the approval of fruquintinib in China in 2018.

However, during the FRESCO study, the standard treatment practices and available therapies for metastatic colorectal cancer in China differed from other regions worldwide.

In China, VEGF inhibitors or epidermal growth factor receptor (EGFR) inhibitors were not included in the routine treatment standards, and regorafenib and trifluridine-tipiracil had not been approved.

Therefore, in FRESCO, only 30% of patients had previously received VEGF inhibitor treatment, 14% had received EGFR antibody treatment, and no patients had received trifluridine-tipiracil treatment. Patients who had received regorafenib treatment were excluded.

A phase 1/1b expansion cohort study of fruquintinib (NCT03251378) is currently being conducted in the United States, which includes patients with metastatic colorectal cancer who have or have not received trifluridine-tipiracil or regorafenib.

Encouraging preliminary anti-tumor efficacy and safety have been observed, further supporting the investigation of fruquintinib in the population of refractory metastatic colorectal cancer.

Research progress

A total of 691 patients were included in the study, and the enrollment was divided into fruquintinib treatment group (5mg QD) or placebo group according to the ratio of 2:1.

Other designs were consistent with typical randomized controlled clinical trials. The main endpoint of the study was total Survival (OS), progression-free survival (PFS) were key secondary endpoints.

FRESCO-2 study design sketch

In terms of the primary endpoint OS, when the median follow-up time reached 11.3 months, the median OS of patients in the fruquintinib group was 7.4 months, compared with 4.8 months in the placebo group, and fruquintinib significantly prolonged the median OS of 2.6 months. The OS was lowered by 34% in the risk of death.

Fruquintinib can reduce the risk of death by 34% on advanced colorectal cancer OS curve

The analysis of the secondary endpoint progression-free survival (PFS) showed that the median PFS in the fruquintinib group was 3.7 months, which was also significantly longer than that in the placebo group (1.9 months) (HR=0.32, P<0.0001), and the OS Both subgroup analysis and PFS analysis indicated that all subgroups of patients could benefit significantly from fruquintinib treatment.

In addition, in terms of disease control rate (DCR), 55% in the fruquintinib group was also significantly higher than 16% in the control group.

The treatment safety of fruquintinib was consistent with expectations, and no new safety signal was found, and the treatment time of patients in the treatment group was longer than that of the placebo group (3.1 months/1.8 months), suggesting that the overall tolerance was still low.

It is worth mentioning that the median number of previous systemic treatments for patients enrolled in the FRESCO-2 study was 4, and more than 90% of the patients had received TAS-102 treatment, and nearly half of the patients (48%) had used Regal Fini means that fruquintinib is actually used as a third-line or above third-line treatment, and the challenge it faces is greater than that of the FRESCO study.

Significance

This study demonstrates that targeted inhibition of VEGFRs with fruquintinib is a safe and effective treatment for metastatic disease that has progressed on or is intolerant to trifluridine-tipiracil or regorafenib or both patients with colorectal cancer.

The results presented here support those of previous studies showing the efficacy and tolerability of fruquintinib monotherapy in patients with fewer lines of prior therapy, such as FRESCO.

Therefore, the totality of evidence for fruquintinib supports its use in multiple settings and it should be considered a new global treatment option for patients with chemotherapy-refractory metastatic colorectal cancer who have few treatment options.

Further research is needed to determine the optimal sequencing strategy for patients who have failed at least two lines of therapy.

References:

https://doi.org/10.1016/S0140-6736 (23) 00772-9

Fruquintinib can reduce the risk of death by 34% on advanced colorectal cancer

(source:internet, reference only)

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