1967P - A single-arm multicenter trial of the combination of anlotinib with chemotherapy in patients with stage IIb classic osteosarcoma of the extremity

Background

Clinical studies have shown overexpression of multiple tyrosine kinase receptors on the surface of osteosarcoma samples. Anlotinib is a multi-targeted tyrosine kinase inhibitor. The combination of anti-angiogenic drugs with chemotherapeutic agents theoretically has the ability to act synergistically. We conducted this trial to explore the efficacy and safety of anlotinib in combination with chemotherapy for treatment naive stage IIB classical osteosarcoma of the extremity.

Methods

This is a multicentric, single-arm, open-lable trial. Eligible patients(pts) were aged 12-40 years with histologically diagnosed primary localized extremity classic osteosarcoma, stage IIB, operable. Pts received anlotinib (10mg, q3w), doxorubicin(A) and cisplatin(P) for the first nine weeks. Pts underwent radical surgery after exclusion of contraindications at week 10. After surgery, pts received AP at weeks 12-14, and anlotinib plus AP at weeks 15-20, drug dose unchanged. Since week 21, anlotinib(12mg) monotherapy was maintained until week 104 or occurrence of an EFS event. The primary endpoint was 24-month EFS rate, secondary endpoints were 36-month EFS rate, local recurrence rate, lung metastasis rate, 3-year OS Rate and safety.

Results

From May 2020 to Apr 2022, 52 eligible pts were enrolled. At the data cut-off date (Mar 2023), 51 pts underwent surgery after 3 cycles of neoadjuvant therapy, while the rates of limb salvage and R0 resection were 80.39%(95%CI:66.88-90.18%) and 100% (95%CI: 93.02-100%), respectively. In best overall response assessment during the neoadjuvant period, ORR was 1.92% (95%CI: 0.05-10.26%) and DCR was 96.15% (95%CI: 86.79-99.53%). The median EFS was not reached, 12 and 18month-EFS rate were 89.03% (95%CI: 75.39-95.33%) and 59.35% (95%CI: 8.64, 89.48%), respectively. The most grade 3/4 treatment-emergent adverse events were neutropenia (46.15%), leukopenia (36.54%), thrombocytopenia (32.69%), anemia (30.77%).

Conclusions

Preliminary results suggested that anlotinib combined with doxorubicin and cisplatin followed by surgery showed favorable efficiency and manageable adverse events in Stage IIB classic osteosarcoma of the extremity.

Clinical trial identification

ChiCTR2000033298.

Editorial acknowledgement

Legal entity responsible for the study

West China School of Medicine/West China Hospital of Sichuan University (WCSM/WCH).

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.