1743P - A phase II study of fruquintinib in the 1L or 2L treatment of unresectable metastatic soft tissue sarcoma

Background

Soft tissue sarcomas are rare yet highly morbid malignancies with intricate subtype classifications. It is urgent to explore specific regimens suitable for different subtypes. First line therapy for metastatic STS remains anthracycline-based cytotoxic chemotherapy, effective second-line treatment options are limited. This limitation become more prominent for sarcoma subtypes insensitive to chemotherapy or patients who are intolerance to chemotherapy. We assessed if Fruquintinib, a highly selective tyrosine kinase inhibitor of VEGFR-1, -2, and -3 is effective and safe in the 1L or 2L treatment for these patients with specific soft tissue sarcoma subtypes.

Methods

This is a single-arm, prospective, single-center clinical study. The inclusion criteria were patients with pathologically confirmed unresectable metastatic STS including epithelioid hemangioendothelioma (EHE), solitary fibroma tumor (SFT), hemangiopericytoma (HPC) and chemotherapy-failed angiosarcoma (AS), at least one measurable lesion (according to RECIST 1.1), with the normal function of main organs. Other inclusion criteria included ECOG PS 0-2 and anti-angiogenesis treatment naïve. Patients were administrated 5mg Fruquintinib once daily for 3 weeks every 4 weeks until disease progression or intolerable toxicity. The primary study endpoint was PFS. ORR, DCR and adverse event were also calculated.

Results

From November 4, 2021 to April 25, 2024, a total of 32 patients (16 males and 16 females) were enrolled. The median age is 53. Pathological types included: EHE (n=13), AS (n=10), SFT (n=8) and HPC (1). 31 patients were eligible for the evaluation of tumor response. The median PFS was 7.4 months. 1 patient (AS) achieved complete remission. 7 patients (2 cases of EHE, 4 cases of AS and 1 case of SFT) achieved partial response and the ORR was 25.8 % (8/31). 20 patients had stable disease and the DCR was 93.5% (29/31). The most common TEAE (treatment emergent adverse event) were hypertension, fatigue, and hemorrhage. The most common Grade 3/4 TEAE is hypertension and abnormal liver function.

Conclusions

The Fruquintinib showed a promising efficacy and favorable tolerance in 1L or 2L treatment of unresectable metastatic STS.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Hutchmed Ltd.

Disclosure

All authors have declared no conflicts of interest.