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Outcome of Patients With Recurrent Osteosarcoma Enrolled in Seven Phase II Trials Through Children's Cancer Group, Pediatric Oncology Group, and Children's Oncology Group: Learning From the Past to Move Forward
Open accessAbstract
Purpose: The use of radiographic response as the primary end point in phase II osteosarcoma trials may limit optimal detection of treatment response because of the calcified tumor matrix. We performed this study to determine if time to progression could be used as an end point for subsequent studies. Patients and Methods: We performed a retrospective analysis of outcome for patients with recurrent/refractory osteosarcoma enrolled in one of seven phase II trials conducted by the Children’s Oncology Group and predecessor groups from 1997 to 2007. All trials used RECIST or WHO radiographic response criteria and the primary end point of response rate. The following potential prognostic factors—age, trial, number of prior chemotherapy regimens, sex, and race/ethnicity—were evaluated for their impact on event-free survival (EFS). We used data from a phase II study (AOST0221) of patients with osteosarcoma who were given inhaled granulocyte-macrophage colony-stimulating factor with first pulmonary recurrence who had an EFS as well as biologic end point to determine the historical disease control rate for patients with fully resected disease. Results: In each included trial, the drugs tested were determined to be inactive on the basis of radiographic response rates. The EFS for 96 patients with osteosarcoma and measurable disease was 12% at 4 months (95% CI, 6% to 19%). There was no significant difference in EFS across trials according to number of prior treatment regimens or patient age, sex, and ethnicity. The 12-month EFS for the 42 evaluable patients enrolled in AOST0221 was 20% (95% CI, 10% to 34%). Conclusion: The EFS was uniformly poor for children with recurrent/refractory osteosarcoma in these single-arm phase II trials. We have now constructed baseline EFS outcomes that can be used as a comparison for future phase II trials for recurrent osteosarcoma.
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“the observed tumor stabilization was important, and approximately 40% of the patients remained progression–free for more than 5 months, which qualifies as active treatment in the setting of high‐grade sarcomas. 39 , 40 , 41 , 42”
From Nivolumab and sunitinib in patients with advanced bone sarcomas: A multicenter, single‐arm, phase 2 trial (2025) · cites this paper as [41]
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“approximately 40% of the patients remained progression–free for more than 5 months”
From Nivolumab and sunitinib in patients with advanced bone sarcomas: A multicenter, single‐arm, phase 2 trial (2025) · cites this paper as [41]
In the citing paper
“For patients with unresectable or refractory osteosarcoma following first-line chemotherapy, prognosis remains poor, with 5-year post-relapse survival rates below 20%16,17.”
In the citing paper
“For comparison, a 4-month PFS of 0% in the control arm of the phase II trials of regorafenib and of 15% for a historical benchmark established by a pooled analysis of 96 patients with osteosarcoma and measurable disease enrolled on seven Children's Oncology Group phase II trials were observed 152 .”
From Osteosarcoma (2022) · cites this paper as [152]
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Metadata
- Authors
- Lagmay, J. P., Krailo, M. D., Dang, H., Kim, A., Hawkins, D. S., Beaty, O., Widemann, B. C., Zwerdling, T., Bomgaars, L., Langevin, A.-M., Grier, H. E., Weigel, B., Blaney, S. M., Gorlick, R., & Janeway, K. A.
- Affiliations
- University of Southern California (US)
- ORCID
- Venue
- Journal of Clinical Oncology
- Published
- 2016-09-01
- Volume
- 34
- Issue
- 25
- Pages
- 3031-3038
- ISSN
- 0732-183X (ISSN-L)
- 1527-7755
- PMC
- PMC5012712
- OpenAlex
- W2473766695
- Cited by
- 190
- References
- 33
- Citations by year
- 2026: 11 · 2025: 20 · 2024: 23 · 2023: 25 · 2022: 19 · 2021: 27 · 2020: 19 · 2019: 16 · 2018: 14 · 2017: 10 · 2016: 5
- FWCI
- 13.42
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Clinical Oncology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Children’s Oncology Group (U10 CA180886, U10 CA180899)
- National Cancer Institute (U10 CA-98413, U10-CA98543, U10CA098413, U10CA180899, U10CA180886, U10CA098543)
- Topics
- Health Sciences › Medicine › Oncology › Sarcoma Diagnosis and Treatment
- Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone Tumor Diagnosis and Treatments
- Health Sciences › Medicine › Hematology › Acute Lymphoblastic Leukemia research
- Keywords
- recurrent osteosarcoma, event-free survival, time to progression, prognostic factors, pediatric oncology, GM-CSF
- MeSH terms
- Adolescent, Bone Neoplasms, Child, Female, Humans, Male, Neoplasm Recurrence, Local, Retrospective Studies, Osteosarcoma, Treatment Outcome, Clinical Trials, Phase II as Topic, Disease-Free Survival, Endpoint Determination
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