Apatinib plus ifosfamide and etoposide for relapsed or refractory osteosarcoma: A retrospective study in two centres

Abstract

For osteosarcoma that progresses following first-line chemotherapy, prognosis remains poor although anti-angiogenesis tyrosine kinase inhibitors (TKIs) have been verified to prolong progression-free survival. Apatinib has led to positive responses in the treatment of refractory osteosarcoma. However, it demonstrates only short-lived activity, and the disease control rate of musculoskeletal lesions is worse compared with that of pulmonary lesions. This treatment failure has been partly overcome by the addition of ifosfamide and etoposide (IE). The present study retrospectively compared the activity of apatinib + IE in relapsed or refractory osteosarcoma in two sarcoma centres in China. The included patients had received a combination of apatinib 500 mg (orally) daily and the IE regimen (n=33) between June 3 2017 and July 17 2020. The tumour burden was considerable in these patients: 16/33 (48.5%) Patients had lung and musculoskeletal lesions, and 31/33 (93.9%) patients had progressed to two lines of therapies at baseline. With a median follow-up duration of 28.4 [interquartile range (IQR), 16.1-38.3] months, 21/33 (63.6%) patients had objective responses, and the median event-free survival was 11.4 (IQR, 6.7-18.4) months. The median overall survival time was 19.8 (IQR, 13.1-30.6) months. At the last follow-up, 16/33 patients had tumour downstaging, and all lesions had been completely resected. For osteosarcoma with multiple sites of metastasis, apatinib + IE demonstrated clinically meaningful antitumor activity and delayed disease progression in patients with recurrent or refractory osteosarcoma after failure of chemotherapy. This combination with manageable toxicity deserves further investigation in prospective trials.

Various Expression and Clinical Significance of Checkpoint Molecules in Advanced Osteosarcoma: Possibilities for Novel Immunotherapy

“…We usually conducted our first-line chemotherapy following the Peking University 166 People's Hospital-Osteosarcoma (PKUPH-OS 02) regimen (Additional file 3: Fig. S1) 167 [24,25], which included high-dose methotrexate, doxorubicin, cisplatin, and 168 ifosfamide. Our second-line chemotherapy was usually ifosfamide (1.8 g/m 2 /d d1-5) and regorafenib [24,25].…”

“…S1) 167 [24,25], which included high-dose methotrexate, doxorubicin, cisplatin, and 168 ifosfamide. Our second-line chemotherapy was usually ifosfamide (1.8 g/m 2 /d d1-5) and regorafenib [24,25]. For this group of patients, 14/35 (40%) had been confirmed 172 to be refractory to first-and second-line chemotherapy, while 4/35 (11.4%) had been progressive upon TKI therapy.…”

“…The clinicopathological characteristics of the patients included in the study are summarized in Table 1. All these patients were in a metastatic or refractory state, and their disease had progressed upon first-line chemotherapy [24,25]. The median age at diagnosis was 14 (interquartile range (IQR), 6,22) years.…”

“…We usually conducted our first-line chemotherapy following the Peking University People's Hospital-Osteosarcoma (PKUPH-OS 02) regimen (Additional file 3: Fig. S1) [24,25], which included high-dose methotrexate, doxorubicin, cisplatin, and ifosfamide. Our second-line chemotherapy was usually ifosfamide (1.8 g/m 2 /d d1-5) and etoposide (100 mg/m 2 /d d1-5 Q3W), while our third-line systemic therapy was usually antiangiogenic tyrosine kinase inhibitor (TKI)-based therapy, such as apatinib and regorafenib [24,25].…”

“…S1) [24,25], which included high-dose methotrexate, doxorubicin, cisplatin, and ifosfamide. Our second-line chemotherapy was usually ifosfamide (1.8 g/m 2 /d d1-5) and etoposide (100 mg/m 2 /d d1-5 Q3W), while our third-line systemic therapy was usually antiangiogenic tyrosine kinase inhibitor (TKI)-based therapy, such as apatinib and regorafenib [24,25]. For this group of patients, 14/35 (40%) had been confirmed to be refractory to first-and second-line chemotherapy, while 4/35 (11.4%) had been progressive upon TKI therapy.…”