Camrelizumab in combination with doxorubicin, cisplatin, ifosfamide, and methotrexate in neoadjuvant treatment of resectable osteosarcoma: A prospective, single‐arm, exploratory phase II trial

• Published in: Cancer medicine (Malden, MA) Vol. 13; no. 18; pp. e70206 - n/a
• Main Authors: Tang, Qinglian, Zhang, Xinke, Zhu, Xiaojun, Xu, Huaiyuan, Song, Guohui, Lu, Jinchang, Wu, Hao, Deng, Chuangzhong, Ai, Fei, Zhang, Yingchun, Wang, Jin
• Format: Journal Article
• Language: English
• Published: United States John Wiley & Sons, Inc 01.09.2024; John Wiley and Sons Inc
• Subjects: Adolescent; Adult; Adverse events; Antibodies; Antibodies, Monoclonal, Humanized - administration & dosage; Antibodies, Monoclonal, Humanized - adverse effects; Antibodies, Monoclonal, Humanized - therapeutic use; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Bone cancer; Bone Neoplasms - drug therapy; Bone Neoplasms - mortality; Bone Neoplasms - pathology; Bone Neoplasms - therapy; camrelizumab; Cancer therapies; Chemotherapy; Cisplatin; Cisplatin - administration & dosage; Cisplatin - therapeutic use; Doxorubicin; Doxorubicin - administration & dosage; Doxorubicin - therapeutic use; Female; Hematology; Humans; Ifosfamide; Ifosfamide - administration & dosage; Ifosfamide - therapeutic use; Immunotherapy; Leukocytes; Lymphocytes; Male; Medical prognosis; Methotrexate; Methotrexate - administration & dosage; Methotrexate - therapeutic use; Middle Aged; Mucositis; Necrosis; neoadjuvant therapy; Neoadjuvant Therapy - methods; Osteosarcoma; Osteosarcoma - drug therapy; Osteosarcoma - mortality; Osteosarcoma - surgery; Osteosarcoma - therapy; Patients; programmed cell death receptor 1; Prospective Studies; Surgery; Tumors; Young Adult; programmed cell death receptor 1; neoadjuvant therapy; osteosarcoma; camrelizumab
• ISSN: 2045-7634; 2045-7634
• DOI: 10.1002/cam4.70206

Background The poor overall survival of osteosarcoma (OS) underscores the need to explore new therapeutic avenues. Tumor necrosis rate (TNR) after neoadjuvant chemotherapy predicts prognosis. Aims The study was to investigate safety and activity of neoadjuvant chemotherapy with camrelizumab (a humanized antibody against PD‐1) in patients with resectable OS. Materials & Methods We conducted a prospective, single‐arm, exploratory phase II trial in OS patients. Eligible patients received camrelizumab combined with doxorubicin or liposomal doxorubicin, cisplatin, methotrexate, ifosfamide with mesna. Surgery was performed 12–14 days after neoadjuvant therapy and adjuvant therapy starting 2–3 weeks postoperatively. The primary endpoint was the rate of good tumor necrosis (TNR ≥90%) after neoadjuvant therapy, and the secondary outcomes were safety, 2‐year progression free survival and 2‐year overall survival. Results Seventy‐five patients were recruited to the study. Subsequently, 64 patients completed neoadjuvant therapy and underwent surgery. Thirty‐one patients (48.4%) have a good TNR to neoadjuvant therapy. With a median follow‐up of 22.4 months (range 2.2–44.9 months), the estimated 2‐year PFS was 69.6% and the estimated 2‐year overall survival was 89.4%. Grade 3 or 4 treatment‐related adverse events were noticed in 62.7% of the patients. Frequent grade 3 or 4 adverse events were decreased platelet count (45.3%), decreased white blood cell count (36%). No immune‐related serious adverse events were observed. Discussion Our study had limitations. First, it was limited by its non‐randomized design. Besides, stromal tumor‐infiltrating lymphocytes was comprehensively analyzed in this study. Conclusions This study demonstrated that amrelizumab combined with adriamycin, cisplatin, methotrexate, and ifosfamide in the neoadjuvant treatment of resectable OS was safe and tolerable. This combined therapeutic strategy may not increase TNR, but the long‐term survival benefit remains to be followed up.