Apatinib plus ifosfamide and etoposide versus ifosfamide and etoposide in patients with advanced osteosarcomas (OAIE/PKUPH-sarcoma 11): a randomized phase II study
Relapsed or refractory osteosarcoma carries a poor prognosis after standard chemotherapy. We conducted a multicenter, randomized, phase II trial (NCT05277480) to compare apatinib plus ifosfamide/etoposide (IE) with IE alone in patients who had progressed following at least one prior line of chemotherapy. Patients were randomized 2:1 to receive apatinib (500 mg orally once daily) plus IE (ifosfamide 1.8 g/m²/day and etoposide 100 mg/m²/day, days 1-3 every 3 weeks) or IE alone (same doses, days 1-5 every 3 weeks). The primary endpoint was progression-free survival (PFS). Between April 14, 2022, and August 22, 2023, 81 patients were enrolled (53 in apatinib plus IE group and 28 in IE group). After a median follow-up of 19.9 months, the median PFS was 5.5 months (95% confidence interval [CI]: 3.9, 6.4) with apatinib plus IE compared with 3.4 months (95% CI: 1.4, 4.6) with IE (hazard ratio, 0.60; 95% CI: 0.37, 0.98; P = 0.0402). The trial met its pre-specified primary endpoint. These results suggest that apatinib plus IE may improve PFS in relapsed or refractory osteosarcoma, but as a randomized phase II study, the findings are exploratory and require confirmation in phase III trials.
Authors
- Jie Xu (ORCID: https://orcid.org/0000-0003-1957-8438)
- Haiyan Hu (ORCID: https://orcid.org/0000-0002-3993-974X)
- Shurong Shao
- Yingqi Hua (ORCID: https://orcid.org/0000-0002-7277-0958)
- Zheling Chen (ORCID: https://orcid.org/0000-0002-3073-1811)
- Xin Sun (ORCID: https://orcid.org/0000-0001-5902-9949)
- Xiaodong Tang (ORCID: https://orcid.org/0000-0002-9097-3249)
- Kuisheng Liu (ORCID: https://orcid.org/0000-0002-0870-4390)
- Sujia Wu
- Pan Zheng (ORCID: https://orcid.org/0000-0003-2598-3544)
- Lu Xie (ORCID: https://orcid.org/0000-0001-7241-1915)
- Yuan Li (ORCID: https://orcid.org/0000-0001-7542-3815)
- Ran Wei (ORCID: https://orcid.org/0000-0003-4040-0087)
- Guangxin Zhou (ORCID: https://orcid.org/0000-0002-0252-2473)
- Rong Liu (ORCID: https://orcid.org/0000-0002-4484-5203)
- Wei Guo
- Tao Ji (ORCID: https://orcid.org/0000-0001-6876-7361)
- Du Wang
- Kunkun Sun (ORCID: https://orcid.org/0000-0002-4530-5778)
- Yi Yang (ORCID: https://orcid.org/0000-0003-2879-4968)
Institutions
- Shanghai Jiao Tong University (CN)
- Peking University (CN)
- Peking University People's Hospital (CN)
- Shanghai First People's Hospital (CN)
- Shanghai Sixth People's Hospital (CN)
- Jiangsu Hengrui Medicine (China) (CN)
- Nanjing Medical University (CN)
- Nanjing University (CN)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-11-25
- DOI
- https://doi.org/10.1038/s41467-025-65467-8
- Primary Topic
- Sarcoma Diagnosis and Treatment
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Peking University
- Peking University People's Hospital
- National Science and Technology Major Project