Efficacy and Safety of Fruquintinib-Based Treatment in Patients with Refractory Bone and Soft Tissue Sarcoma after
Chenchen Yang1, Binghao Li2, Sen Dong1
1Musculoskeletal Tumor Center, Peking University People's Hospital, Beijing, China.
Objective:
Multitargeted tyrosine kinase inhibitors (TKIs) have been approved as second-line therapy in refractory sarcoma, prolonging progression-free survival (PFS) but with short-lived duration of disease control. Fruquintinib is a TKI that specifically inhibits vascular endothelial growth factor receptor-1,2,3 with no metabolism by liver enzymes. In this retrospective study, we assessed the efficacy and safety of fruquintinib-based treatment in patients with refractory sarcoma after developing several lines of TKI resistance.
Methods:
We retrospectively analyzed the clinical data of patients with refractory sarcoma after they had developed several lines of resistance to TKIs and who received fruquintinib-based treatment from November 2021 to August 2023. The primary endpoint was the progression-free survival rate at 4 months (4m-PFSR). Secondary endpoints were the median PFS, overall survival (OS), objective response rate, disease control rate, and adverse effects (AEs). PFS and OS were estimated using the Kaplan-Meier method. A log-rank test was used to compare survival curves between different clinical and pathological factors. Cox proportional hazards analysis was performed to identify PFS-related prognostic factors.
Results:
We included 124 patients: 56 (45.2%) with osteosarcoma, 28 (22.6%) with Ewing sarcoma, seven (5.6%) with chondrosarcoma, and 33 (26.6%) with soft tissue sarcomas (STS). Only 18 (14.5%) patients received monotherapy with fruquintinib. With a median follow-up time of 6.8 (interquartile range [IQR], 4.6-9.4) months, 22 (17.7%) patients had partial response and 78 (62.9%) had stable disease. The 4m-PFSR was 58.4% (95% confidence interval [CI], 49.6%-67.1%). The median PFS and OS were 4.4 (95% CI, 3.9-5.0) months and 11.4 (95% CI, 10.3-12.5) months. In multivariate analysis, a high hazard ratio for progression was associated with target lesions located outside the lung and bone with 1.79 (95% CI, 1.10-2.93; p = 0.020). Eighty-eight AEs were recorded in 47 (37.9%) patients; the most common were pneumothorax (18/124, 14.5%), diarrhea (8/124, 6.5%), oral mucositis (7/124, 5.6%), and thrombocytopenia (7/124, 5.6%).
Conclusions:
Fruquintinib may be a potential option for patients with refractory sarcoma after developing several lines of TKI resistance, with a satisfactory efficacy and safety profile in combination therapy. However, the degree of contribution of fruquintinib to results is unclear when combined with other effective substances. Additional prospective trials of fruquintinib should be conducted, especially involving different pathological types and combination regimens.
Insights
Fruquintinib shows promise for refractory sarcoma patients resistant to tyrosine kinase inhibitors (TKIs). This study found a 58.4% progression-free survival rate at 4 months, suggesting a potential new treatment option.
Area of Science:
- Oncology
- Pharmacology
Background:
- Multitargeted tyrosine kinase inhibitors (TKIs) offer limited disease control in refractory sarcoma.
- Fruquintinib, a novel TKI, inhibits VEGFRs without hepatic metabolism.
Purpose of the Study:
- To assess the efficacy and safety of fruquintinib-based treatment in patients with refractory sarcoma after multiple TKI resistance lines.
- To evaluate progression-free survival (PFS), overall survival (OS), response rates, and adverse events.
Main Methods:
- Retrospective analysis of 124 refractory sarcoma patients treated with fruquintinib from November 2021 to August 2023.
- Primary endpoint: 4-month PFS rate (4m-PFSR). Secondary endpoints: median PFS, OS, objective response rate, disease control rate, and adverse effects (AEs).
- Survival analysis using Kaplan-Meier and Cox proportional hazards models.
Main Results:
- The 4m-PFSR was 58.4%. Median PFS was 4.4 months and median OS was 11.4 months.
- Objective response rate was 17.7% (partial response) and 62.9% had stable disease.
- Common AEs included pneumothorax (14.5%), diarrhea (6.5%), oral mucositis (5.6%), and thrombocytopenia (5.6%).
Conclusions:
- Fruquintinib-based therapy demonstrates a satisfactory efficacy and safety profile for refractory sarcoma patients with TKI resistance.
- Further prospective trials are warranted to clarify fruquintinib's specific contribution and explore combination regimens across diverse sarcoma types.
