Preliminary results of anlotinib combined with gemcitabine and docetaxel for recurrent or metastatic primary malignant bone tumors: An open-label, single-arm, multicenter clinical trial.

e23507 Background: Recurrent or metastatic primary malignant bone tumors were associated with poor prognosis and limited treatment options. Anlotinib, a multiargeted tyrosine kinase inhibitor, has shown antitumor activity in various malignancies. This study aimed to evaluate the efficacy and safety of anlotinib combined with gemcitabine and docetaxel in patients with recurrent or metastatic primary malignant bone tumors. Methods: This open-label, single-arm, multicenter trial enrolled patients aged 5-70 years with recurrent or metastatic primary malignant bone tumors (osteosarcoma, undifferentiated pleomorphic sarcoma, or malignant fibrous histiocytoma) who had progressed on prior systemic therapy and were ineligible for curative surgery. Patients were required to have measurable lesions and an ECOG PS of 0-1 (or 0–2 for amputees). Treatment consisted of anlotinib (10 mg/day for BSA≥1.0 m² or 8 mg/day for BSA<1.0 m², orally, days 1-14), gemcitabine (675 mg/m², IV on days 1 and 8) and docetaxel (75 mg/m², IV on day 8) every 21 days for up to 8 cycles. Intolerant patients switched to maintenance anlotinib (12 mg/day for BSA≥1.0 m²or 10 mg/day for BSA<1.0 m², orally, days 1-14) until progression or intolerance. The primary endpoint was PFS by RECIST 1.1, secondary endpoints included OS, ORR, DCR, and safety. Results: From September 2022 to December 2024, 29 patients were enrolled. The median age was 23.5 years (range: 14-67), with most patients having an ECOG PS of 1 (n = 25, 86.2%) and being male (n = 19, 65.5%). Lung metastasis was most common metastatic site (n = 23, 79.31%). Among 25 evaluable patients, 8 achieved PR, 12 had SD, and 5 experienced PD, resulting in an ORR of 32%, and a DCR of 80%. As of December 31, 2024, the median PFS was 7.13 months (95% CI: 3.94-10.32 months) and median OS had not been reached (longest OS: 17.94 months). The most common adverse events included leukopenia (48.3%), anemia (34.5%), neutropenia (31.0%), thrombocytopenia (31.0%), diarrhea (31.0%), and fever (31.0%). Grade ≥3 events included neutropenia (24.1%), leukopenia (17.2%), thrombocytopenia (13.8%), lymphopenia (10.3%), and anemia (3.5%). No treatment-related deaths were reported. Conclusions: Anlotinib combined with gemcitabine and docetaxel demonstrated promising antitumor activity and an acceptable safety profile in patients with recurrent or metastatic primary malignant bone tumors. Further studies are warranted to confirm these findings and explore the optimal treatment regimen. Clinical trial information: ChiCTR2200058759 .