Abstract
PURPOSE: The options for the second-line treatment of metastatic osteosarcoma are still limited. Anlotinib is a multi-kinase inhibitor which has shown promising efficacy and good tolerability in various cancer types. This retrospective study was conducted to evaluate the efficacy and safety of anlotinib combined with gemcitabine/docetaxel (GD) in patients with metastatic osteosarcoma who have failed first-line chemotherapy. PATIENTS AND METHODS: The data of patients who received anlotinib combined with GD or GD were collected. The primary endpoint was progression-free survival. Secondary endpoints included objective response rate and safety. RESULTS: From July 2013 to November 2020, a total of 32 patients were enrolled, 13 received anlotinib combined with GD and 19 received GD. Median PFS was 9.0 months (95% CI 6.7-39.1) in the combination group and 5.0 months (95% CI 1.2-6.7) in the chemotherapy group. ORR were 38.4% and 15.8%, DCR were 69.2% and 38.1% in the combination and chemotherapy group, respectively. The most common adverse events included fatigue (78.9% in the combination group vs 69.2% in the chemotherapy group), hypertension (46.2% vs 10.5%), diarrhea (38.5% vs 21.1%), hypothyroidism (38.5% vs 15.8%), neutropenia (23.1% vs 36.8%) and AST elevation (30.8% vs 21.1%). The most common grade 3 or worse adverse events included hand-foot reaction (7.7% vs 5.3%), hypothyroidism (15.4% vs 0), neutropenia (0 vs 10.5%). CONCLUSION: The combination of anlotinib and GD showed favorable efficacy with manageable toxicities compared with GD in the second-line treatment for metastatic osteosarcoma. This combination therapy deserves further investigations in patients with osteosarcoma.