Dataset Information

Efficacy and safety of apatinib in advanced refractory soft tissue sarcoma and association with histologic subtypes: a multicenter retrospective study.

ABSTRACT:

Background

Antiangiogenic therapy is a potential strategy against advanced refractory soft tissue sarcoma (STS). This retrospective study aimed to assess the efficacy and safety of apatinib in patients with advanced refractory STS and explore its clinical effect on the different histologic subtypes.

Methods

Patients with pathologically diagnosed and metastatic STS who had failed at least standard chemotherapy and were naive to angiogenesis inhibitors were enrolled in this multicenter respective study. Apatinib was administered orally at a dosage of 250 to 850 mg/day. The primary endpoints were objective response rate (ORR) and disease control rate (DCR). The secondary endpoints were progression free survival (PFS) and overall survival (OS). Tumor assessment was done after the first 4 weeks and every 8 weeks thereafter.

Results

Twenty-six patients were enrolled from seven centers between December 2015 and December 2020, consisting of 9 leiomyosarcomas (LMS), 4 rhabdomyosarcomas (RMS), 3 undifferentiated pleomorphic cell sarcomas (UPS), 3 fibrosarcomas (FS), 3 alveolar soft part sarcomas (ASPS), 2 angiosarcomas (AS) and 2 synovial sarcomas (SS). The median age was 49.0 [26-77] years, 15 females and 11 males. The ORR was 34.62% [9/26, 95% confidence interval (CI): 19.42-53.78%] and DCR was as high as 84.62% (22/26, 95% CI: 66.47-93.85%). The median progression-free survival and overall survival were 6.0 months (95% CI: 2.42-9.58) and 19.3 months (95% CI: 7.31-31.29) respectively. Furthermore, 181 patients from seven studies as well as this trial were included for pooled analysis of apatinib efficacy dependency on histology. In terms of ORR, RMS (41.7%), ASPS (78.6%), and Ewing sarcoma (40.7%) seemed to benefit more than the other histologic subtypes. Common adverse events (AEs) included hand-foot skin reaction (n=13, 50.0%), hypertension (n=12, 46.15%), proteinuria (n=10, 38.46%). Seven patients (7/26, 26.92%) had grade 3 AEs and no grade 4 AEs occurred. 2 patients (2/26, 7.69%) and 15 patients (15/26, 57.69%) experienced dose withdrawal and dose reduction respectively.

Conclusions

Apatinib showed promising efficacy and a manageable safety profile in patients with advanced refractory STS. In addition, the response to apatinib in STS seemed to be dependent on histology.

SUBMITTER: Wang X

PROVIDER: S-EPMC9577742 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature

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Publications

Efficacy and safety of apatinib in advanced refractory soft tissue sarcoma and association with histologic subtypes: a multicenter retrospective study.

Wang Xiangling X Wang Jian J Sun Baoyong B Sun Yuping Y Liu Ning N Niu Xuecai X Li Chunhua C Li Li L Zhang Qiang Q Hao Jing J Wang Xiuwen X

Annals of translational medicine 20220901 18

<h4>Background</h4>Antiangiogenic therapy is a potential strategy against advanced refractory soft tissue sarcoma (STS). This retrospective study aimed to assess the efficacy and safety of apatinib in patients with advanced refractory STS and explore its clinical effect on the different histologic subtypes.<h4>Methods</h4>Patients with pathologically diagnosed and metastatic STS who had failed at least standard chemotherapy and were naive to angiogenesis inhibitors were enrolled in this multicen ...[more]

PMID: 36267758

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Project description:BackgroundAnti-angiogenic agents have been reported to exert promising clinical activity for advanced soft tissue sarcoma (STS). Apatinib, a vascular endothelial growth factor receptor-2 tyrosine kinase inhibitor, is effective and safe for various solid tumors, but its role in STS remains unclear. The aim of this study was to explore the efficacy and safety of apatinib in patients with untreated or chemotherapy-refractory STS.MethodsIn this multicenter, single-arm, phase 2 trial, patients aged 18-70 years with untreated or chemotherapy-refractory STS were enrolled and received 500 mg apatinib per day. During treatment, patients were followed up with imaging every 8 weeks. The primary endpoint was the 6-month progression-free survival (PFS) rate. The secondary endpoints were objective response rate (ORR), overall survival (OS), and adverse events (AEs), which were graded following the National Cancer Institute common terminology criteria for AEs version 4.03.ResultsFrom June 2017 to October 2018, 53 patients were enrolled, 51 of whom received at least one dose of apatinib. Of the 53 patients, 41 (77.4%) had chemotherapy-refractory disease. The median follow-up was 13.3 months. The 6- and 12-month PFS rates were 46.8% and 25.2%, respectively, with a median PFS of 5.6 months [95% confidence interval (CI): 3.8-9.2 months]. The median PFS was 5.5 months for chemotherapy-refractory patients, 9.1 months for untreated patients, 13.9 months for patients with alveolar soft part sarcoma (ASPS), and 3.7 months for patients with clear cell sarcoma (CCS). The 12- and 24-month OS rates were 58.6% and 44.9%, respectively, with a median OS of 20.0 months (95% CI: 9.2-31.1 months). The median OS was 10.7 months for chemotherapy-refractory patients and not estimated for untreated, ASPS, nor CCS patients. In 50 evaluable patients, the ORR was 18.0% and the disease control rate was 86.0%. These results were similar to those of the per-protocol set. The most common grade 3 or 4 AEs included hypertension [30 (58.8%) of 51 patients], leukopenia [12 (23.5%)], proteinuria [8 (15.69%)], and hematuria [8 (15.69%)]. One patient died of unknown cause.ConclusionsThis study suggested that apatinib might be effective and tolerable in patients with untreated or chemotherapy-refractory STS (NCT03064243).

Project description:ObjectiveMultitargeted 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.MethodsWe 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.ResultsWe 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%).ConclusionsFruquintinib 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.

Dataset Information

Efficacy and safety of apatinib in advanced refractory soft tissue sarcoma and association with histologic subtypes: a multicenter retrospective study.

Background

Methods

Results

Conclusions

Publications

Efficacy and safety of apatinib in advanced refractory soft tissue sarcoma and association with histologic subtypes: a multicenter retrospective study.

Similar Datasets

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