Apatinib + Ifosfamide and Etoposide for Relapsed or Refractory Osteosarcoma

Apatinib+Ifosfamide and Etoposide (IE) Versus IE Alone for Relapsed or Refractory Osteosarcoma: a Real-world Study in Two Centers in China

Today, using a multi-modal approach consisting of preoperative (neoadjuvant) systemic polychemotherapy followed by local surgical therapy and then postoperative (adjuvant) chemotherapy, long-term, disease-free survival can be achieved in 60- 70% of osteosarcoma patients. However treatment options for osteosarcomas, especially in the setting of metastatic or unresectable disease, are very scarce. Apatinib has been proved to be an effective agent to prolong progression-free survival in advanced osteosarcoma. But after 4-6 months' treatment, secondary resistance always occurred with musculoskeletal lesions' progression or new metastasis. Nowadays giving therapeutic doses of IE concurrently with anti-angiogenesis tyrosine kinase inhibitors is a conceptually attractive strategy for treating patients with refractory osteosarcoma according to prospective trial of lenvatinib +IE reported by Gaspar et al at 2019 ESMO and 2020 ESMO. Thus This study was designed to review our experience in real world for off-label use and characterize the toxicity profile of concurrent apatinib+IE and IE alone in patients with relapsed or refractory osteosarcoma.

Inclusion Criteria: histological diagnosis of osteosarcoma (confirmed by central pathological review by an expert pathologist from the Peking University People's Hospital) objective disease progression within 3 months prior to treatment according to RECIST 1.1 previously treated with one to two lines of chemotherapy for metastatic disease have an adequate performance status (adults:Eastern Cooperative Oncology Group [ECOG] performance status of 0-1;children aged >12 years: a score of ≥60% on the Karnofsky performance scale; children aged ≤12 years a score of ≥60% on the Lansky scale) Exclusion Criteria: a life expectancy of less than 3 months patients had to have adequate bone marrow function, normal renal function, normal liver function, and normal pancreatic function no other malignant tumors no malignant pleural and peritoneal effusion

Xie L, Xu J, Sun X, Tang X, Yan T, Yang R, Guo W. Apatinib for Advanced Osteosarcoma after Failure of Standard Multimodal Therapy: An Open Label Phase II Clinical Trial. Oncologist. 2019 Jul;24(7):e542-e550. doi: 10.1634/theoncologist.2018-0542. Epub 2018 Dec 17.