Efficacy and safety of anlotinib hydrochloride in the treatment of advanced bone and soft tissue sarcoma after failure of first-line chemotherapy.

e23504 Background: There were limit treatments for bone and soft tissue sarcomas that have failed chemotherapy. Anlotinib hydrochloride is a multi-targeted receptor of tyrosine kinase inhibitors (TKI), which has shown therapeutic effects on soft tissue sarcoma. Methods: This is a single-arm, prospective, single-center clinical study. The included criteria were patients with pathological diagnose of bone and soft tissue sarcoma, at least one measurable lesion (criteria of RECIST 1.1), failed of more than one line therapy (except for sarcoma subtypes insensitive to chemotherapy), with the normal function of main organs. All patients received 12mg of anlotinib once daily, 2 weeks on and 1 week off until progression or unacceptable toxicity. The primary endpoint was ORR. We also observed PFS, OS, DCR and AEs. Results: From October 2018to October 2020, a total of 40 patients were enrolled. 25 were men and the median age of the patients was 43.28 (8-79) years. The tumor was located on the trunk in 14 cases, on the limbs in 24 cases and on the abdominal wall in 2 cases. 77.5%, 10%, 7.5% and 5% of patients have lung metastases, bone metastasis, liver metastasis and lymph node metastasis, respectively. The main subtypes included synovial sarcoma (20%), alveolar soft tissue sarcoma (15%), osteosarcoma (12.5%), fibrosarcoma (10%), undifferentiated pleomorphic sarcoma (7.5%). 32.5% of patients had received for at least second-line prior therapy and 25% of patients had received apatinib as a previous treatment. The ORR was 15% and the DCR was 77.5%. Patients who had received apatinib had an ORR of 10% and a DCR of 80% in this group. mPFS were 7.0 months (95%CI = 5.07-8.93) and 7.13 months (95%CI = 5.28-8.98) in overall patients and patients who had received apatinib respectively. The mPFS of ASPS, synovial sarcoma, fibrosarcoma, and osteosarcoma were 17.0 months, 8.2 months, 7.1 months, 2.9 months (p = 0.017). The mOS has not been reached. Adverse events were mainly in grades I and II, The ≥3 AEs were hypertension (2.5%), proteinuria (2.5%), leukopenia (2.5%), thrombocytopenia (2.5%), anorexia (2.5%) and elevated transaminase (5.0%). Conclusions: Anlotinib is effective and safe in the treatment of bone and soft tissue sarcoma, and its efficacy is positively correlated with special types (such as ASPS, synovial sarcoma), effectiveness can also be observed in patients who have failed in other targeted therapy. Clinical trial information: NCT04223583.