Treatment strategies for high-grade osteosarcoma with multidrug chemotherapy and resection result in 3-year event-free survival of 60-70%. The most common factors predicting survival are presence of metastases, histological response to preoperative chemotherapy and complete surgical resection. Four of the active drugs in osteosarcoma include cisplatin, doxorubicin, high-dose methotrexate and ifosfamide and this combination (MAPI), given preoperatively and postoperatively, is widely used for the treatment of osteosarcoma in China. Apatinib also has activity in advanced setting and when incorporated into the treatment of patients with metastatic disease seemed to improve progression-free survival. Combination of apatinib and camrelizumab resulted in durable therapuetic effect in selected cases. Though EURAMOUS-1 suggested that changing chemotherapy postoperatively on the basis of histological response did not improve outcomes. The exploratory study with radomised design to compare combination of chemotherapy with target drug or combination of chemotherapy with anti-PD-1 antibody versus standard chemotherapy has not been tried yet. Thus we aim to investigate the efficacy and toxicity of these combiantions versus standard chemotherapy in this study.

Inclusion Criteria:

• Histologically confirmed high-grade osteosarcoma, including second malignancies
• Tumor (primary, metastatic, or both) resectable OR is expected to become resectable after neoadjuvant induction chemotherapy
• Suitable for neoadjuvant chemotherapy and adjuvant chemotherapy
• Performance status - Lansky 50-100% (for patients under 16 years of age); Performance status - WHO or ECOG 0-2 with a life expectancy >3 months
• normal cardiac function (shortening fraction >28%), normal hearing, normal bone marrow as shown by an absolute neutrophil count of at least 1·5 × 10⁹ cells per L (or a white blood cell count of at least 3 × 10⁹ cells per L if neutrophil count is not available), and a platelet count of at least 100 000 platelets per μL
• Patients were also required to have a serum bilirubin concentration of at most less than 1·5 times the upper limit of normal and a normal creatinine concentration for their age as per protocol
• Women of child-bearing potential had to take adequate contraceptive measures and have a negative pregnancy test within 7 days of study entry.

Exclusion Criteria:

• patients who have recieved anti-angiogenic TKIs or anti-PD-1/PD-L1 antibodies
• allergy to chemotherapy or apatinib or camrelizumab
• other severe illness (eg, psychosis or previous history of cardiovascular disease)
• symptomatic or known CNS metastases
• previous or concurrent second primary malignant tumours
• had uncontrolled complications such as diabetes mellitus, coagulation disorders, urine protein ≥ ++, and so on
• had other infections or wounds
• pregnant or breastfeeding.