Apatinib plus ifosfamide and etoposide (IE) versus IE chemotherapy alone for relapsed or refractory osteosarcoma.

Abstract

e23502 Background: Results of previous study showed promising objective response but short-lived activity of apatinib in the treatment of osteosarcoma refractory to first-line chemotherapy, from which we observed the disease control of musculoskeletal lesions were worse than pulmonary lesions. This treatment failure has partly been overcome by the addition of Ifosfamide and etoposide in OLIE study. We aimed to retrospectively compare the activity of apatinib in combination with IE in relapsed or refractory osteosarcoma with synchronous patients receiving IE chemotherapy alone in two sarcoma centers in China. Methods: We retrospectively analyzed medical files and radiographic materials of patients with osteosarcoma relapsed or refractory to first-line chemotherapy, who had received combination of apatinib and IE regimen or IE chemotherapy alone between June 3rd, 2017 and July 17th, 2020. Seventy-nine patients were included, of whom 33 patients received apatinib in combination with IE and 46 patients received single IE chemotherapy. Results: Patients’ tumor burden and general status were obviously different between these two groups with 16/33 (48.5%) patients receiving apatinib+IE having both Lung and musculoskeletal lesions at baseline and 39/46 (84.8%) patients receiving single IE having just pulmonary lesions at baseline. However at last follow up 16/33 (48.5%) of patients receiving apatinib+IE had all lesions resected while 23/46 (50.0%) of patients receiving IE alone had their lesions resected, which might partly due to down-staging of the diseases. With median follow-up time of 28.4 (IQR, 16.1-38.3) months, 21/33 (63.6%) patients receiving apatinib+IE had objective responses while 13/46 (28.3%) patients receiving single IE chemotherapy had responses. The median event-free survivals (EFS) were respectively 11.4 (IQR, 6.7-18.4) months for apatinib+IE and 11.2 (IQR, 4.4-21.8) months for IE alone without significant statistical differences (P = 0.47). The overall survival (OS) was obviously different because of disease stage and tumor burden according to Kaplan-Meier analysis with median OS time of 30.4 (IQR, 21.8-not reached) months for IE alone and 19.8 (IQR, 13.1-30.6) months (P = 0.019). Conclusions: For osteosarcoma with multiple sites’ metastasis, apatinib plus IE demonstrated clinically meaningful antitumor activity in patients with recurrent or refractory osteosarcoma after failure of MAP/I chemotherapy or even single apatinib or IE treatment alone, with a positive effect on delaying disease progression. This combination deserves further investigation in prospective trials with manageable toxicity.