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CLINICAL TRIAL UPDATES
Pediatric Oncology
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Long-Term Outcomes in Patients With Localized Ewing Sarcoma Treated With Interval-Compressed Chemotherapy on Children's Oncology Group Study AEWS0031
Abstract
Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned coprimary or secondary analyses are not yet available. Clinical trial updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.
Long-term outcomes from Children's Oncology Group study AEWS0031 were assessed to determine whether the survival advantage of interval-compressed chemotherapy (ICC) was maintained over 10 years in patients with localized Ewing sarcoma (ES). AEWS0031 enrolled 568 eligible patients. Patients were randomly assigned to receive vincristine-doxorubicin-cyclophosphamide and ifosfamide-etoposide alternating once every 3 weeks (standard timing chemotherapy [STC]) versus once every 2 weeks (ICC). For this updated report, one patient was excluded because of uncertainty of original diagnosis. The 10-year event-free survival (EFS) was 70% with ICC compared with 61% with STC (P = .03), and 10-year overall survival (OS) was 76% with ICC compared with 69% with STC (P = .04). There was no difference in the 10-year cumulative incidence of second malignant neoplasms (SMNs; PC [see Data Supplement, online only] = .5). A test for interaction demonstrated that ICC provided greater risk reduction for patients with tumor volume ≥200 mL than for patients with tumors <200 mL, but no evidence for a significant interaction in other subgroups defined by age, primary site, and histologic response. With longer-term follow-up, ICC for localized ES is associated with superior EFS and OS without an increased risk for SMN compared with STC. ICC is associated with improved outcomes even in adverse-risk patient groups.
Presented in part at the Connective Tissue Oncology Society (CTOS) Annual Meetings: Salt Lake City, UT, November 4-7, 2015; Lisbon, Portugal, November 9-12, 2016; and Rome, Italy, November 14-17, 2018, and at the ASCO Annual Meeting 2022, Chicago, IL, June 3-7, 2022.
Supported by NCTN Operations Center Grant U10CA180886, NCTN Statistics & Data Center Grant U10CA 180899, St Baldrick's Foundation, and the Daniel P. Sullivan Fund.
NCT00006734 (AEWS0031)
Conception and design: Thomas Cash, Mark D. Krailo, Richard Gorlick, Katherine A. Janeway, Steven G. DuBois, Richard B. Womer
Provision of study materials or patients: Mark D. Krailo, Allen B. Buxton
Collection and assembly of data: Thomas Cash, Mark D. Krailo, Allen B. Buxton, Katherine A. Janeway, Steven G. DuBois, Richard B. Womer
Data analysis and interpretation: Thomas Cash, Mark D. Krailo, Allen B. Buxton, Holcombe E. Grier, Patrick J. Grohar, Damon R. Reed, Aaron R. Weiss, Richard Gorlick, Katherine A. Janeway, Steven G. DuBois, Richard B. Womer
Manuscript writing: All authors
Final approval of manuscript: All authors
Accountable for all aspects of the work: All authors
The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated unless otherwise noted. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/jco/authors/author-center.
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Thomas Cash
Honoraria: EUSA Pharma
Consulting or Advisory Role: Y-mAbs Therapeutics
Research Funding: Celgene (Inst), Roche/Genentech (Inst), Lilly (Inst)
Uncompensated Relationships: United Therapeutics, Lilly
Mark D. Krailo
Consulting or Advisory Role: Merck Sharp & Dohme
Travel, Accommodations, Expenses: Merck Sharp & Dohme
John H. Healey
Honoraria: Stryker, Daiichi Sankyo
Consulting or Advisory Role: Stryker, Daiichi Sankyo
Speakers' Bureau: Stryker
Travel, Accommodations, Expenses: Stryker, Daiichi Sankyo
Other Relationship: Dicephera Pharmaceuticals, Inc
Odion Binitie
Consulting or Advisory Role: Onkos Surgical
Karen J. Marcus
Patents, Royalties, Other Intellectual Property: UpToDate co-author on two Chapters, Associate Editor for Pediatric Blood and Cancer
Patrick J. Grohar
Stock and Other Ownership Interests: AI Therapeutics
Honoraria: Vertex
Consulting or Advisory Role: AI th, InhibRx, Jazz Pharmaceuticals
Research Funding: Janssen Oncology, InhibRx, Jazz/SU2C
Patents, Royalties, Other Intellectual Property: We have a patent pending for mithramycin and analogs as targeted agents for SWI/SNF mutant tumors. It has not issued and is not currently licensed
Damon R. Reed
Consulting or Advisory Role: Eisai, SpringWorks Therapeutics
Aaron R. Weiss
Consulting or Advisory Role: BioAtla
Travel, Accommodations, Expenses: SpringWorks Therapeutics
Richard Gorlick
Research Funding: Eisai (Inst)
Katherine A. Janeway
Honoraria: Foundation Medicine, Takeda
Consulting or Advisory Role: Bayer, Ipsen, Illumina
Travel, Accommodations, Expenses: Bayer
Steven G. DuBois
Consulting or Advisory Role: Bayer, Amgen, Jazz Pharmaceuticals
Research Funding: Merck (Inst), Roche/Genentech (Inst), Lilly (Inst), Curis (Inst), Loxo (Inst), BMS (Inst), Eisai (Inst), Pfizer (Inst), Turning Point Therapeutics (Inst), Bayer (Inst), Salarius Pharmaceuticals (Inst)
Travel, Accommodations, Expenses: Roche/Genentech, Salarius Pharmaceuticals
Uncompensated Relationships: Y-mAbs Therapeutics, Inc
No other potential conflicts of interest were reported.
Research Sponsor:
