Efficacy And Safety Of Apatinib In The Treatment Of Advanced Soft Tissue Sarcoma

【Objective】To evaluate the efficacy and safety of Apatinib Mesylate in the treatment of advanced soft tissue sarcoma,and to explore the possible predictive indicators of efficacy,so as to provide new strategies and experimental basis for clinical treatment of advanced advanced soft tissue sarcoma.【Methods】A retrospective study was conducted to collected patients with advanced soft tissue sarcoma who were admitted to Union Hospital,Tongji Medical College,Huazhong University of Science and Technology from January 2017 to August 2019,and patients treated with Apatinib orally after progression were screened.The main end point was the median progression-free survival,and the secondary end points were objective remission rate,disease control rate and adverse events.The median progression-free survival time of patients treated with Apatinib was calculated by Kaplan-Meier survival analysis,the safety was evaluated according to the Common Terminology Criteria for Adverse Events.COX proportional hazard model was used to analyze the correlation between adverse events and efficacy.【Result】1)A total of 54 patients were included in the study from January 2017 to August2019,of which 54 met the criteria,consisted of 28 males and 26 females,with an average age of 38.5 ± 17.9 years.The median follow-up time was 8.6 months.The pathological subtypes included alveolar soft tissue sarcoma(n = 10),synovial sarcoma(n = 7),leiomyosarcoma(n = 7),rhabdomyosarcoma(n = 6),malignant small round cell tumors(n = 5),undifferentiated pleomorphic sarcoma(n = 4),liposarcoma(n = 4),angiosarcoma(n = 3),malignant solitary fibrous tumor(n = 2)and clear cell sarcoma(n = 2).Fibrosarcoma,follicular dendritic cell sarcoma,epithelioid sarcoma and epithelioid malignant peripheral nerve sheath tumor were 1case for each.2)Efficacy analyses were performed of 54 patients included in the study.One patient achieved complete response,10 patients achieved partial response and 34 patients achieved stable disease.The objective response rate was 20.4%,and the disease control rate was 83.3%.Alveolar soft tissue sarcoma was the subtype with the best efficacy,and the objective response rate and disease control rate were 30% and100%,respectively.The efficacy of malignant small round cell tumor and angiosarcoma was poor,and the objective response rate and the disease control rate were 0% and 80.0%,0% and 33.3%,respectively.The objective response rate and the disease control rate of leiomyosarcoma,synovial sarcoma,rhabdomyosarcoma,undifferentiated pleomorphic sarcoma and liposarcoma were 14.3% and 85.7%,28.6% and 71.4%,16.6% and 83.8%,25.0% and 100%,25.0% and 75.0%,respectively.3)The primary endpoint(median progression-free survival)was 5.8 months for the overall intention-to-treat population.According to subtype analysis,the median progression-free survival of alveolar soft tissue sarcoma,undifferentiated pleomorphic sarcoma and leiomyosarcoma was 24.3 months,8.3 months and 7.4months,respectively.The median progression-free survival of others subtypes was less than 5.8 months.The median progression-free survival for all patients excludingthe dominant subtype of alveolar soft tissue sarcoma was 4.8 months.4)The most common hematological adverse events were leukopenia(40.7%)and anemia(38.9%).The most common non-hematological adverse events were hand-foot syndrome(55.6%),elevated bilirubin(48.1%)and hypertension(46.3%).Most of adverse events were grades Ⅰ to Ⅱ.Grade Ⅲ to Ⅳ hematological adverse events with a proportion exceeding 5% were anemia(13.0%),thrombocytopenia(9.3%),and neutrophils decrease(7.4%)and leukopenia(7.4%).Grade Ⅲ to Ⅳnon-hematological adverse events with a proportion exceeding 5% were hand-foot syndrome(18.5%),hypertension(13.0%),proteinuria(7.4%),diarrhea(5.6%)and oral ulcers(5.6%).5)Analysis of the correlation between grade III to IV non-hematological adverse events with a rate of more than 5% and efficacy showed that the median progression-free survival of patients with and without hand-foot syndrome was 12.5months and 3.4 months,respectively(P < 0.001).The median progression-free survival of patients with and without diarrhea was 35.0 months and 4.5 months,respectively(P < 0.05).The median progression-free survival of patients with and without hypertension was 8.3 months and 4.5 months,respectively(P = 0.067).The median progression-free survival of patients with and without proteinuria was 24.3months and 5 months,respectively(P = 0.067).The median progression-free survival of patients with and without oral ulcers was 35.0 months and 4.5 months,respectively(P = 0.648).【Conclusion】1)The efficacy of Apatinib in the treatment of advanced soft tissue sarcoma satisfactory,the median progression-free survival time was 5.8 months,and the disease control rate was 83.3%,respectively.2)Different pathological subtypes of soft tissue sarcoma respond differently to Apatinib.Alveolar soft part sarcoma was the dominant subtype,followed byundifferentiated pleomorphic sarcoma and leiomyosarcoma.3)Apatinib was safe and basically controllable in treating advanced soft tissue sarcoma.4)Patients with hand-foot syndrome and diarrhea had longer progression-free survival and with hypertension and proteinuria had a tendency to benefit for the progression-free survival when Apatinib was used to treat advanced soft tissue sarcoma.Adverse events after using Apatinib may be used as markers for efficacy prediction.