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

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.