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Clinical Trial
. 2023 Apr 10;41(11):2098-2107.
doi: 10.1200/JCO.22.01815. Epub 2023 Jan 20.

Randomized Phase III Trial of Ganitumab With Interval-Compressed Chemotherapy for Patients With Newly Diagnosed Metastatic Ewing Sarcoma: A Report From the Children's Oncology Group

Steven G DuBois  1 , Mark D Krailo  2 , Julia Glade-Bender  3 , Allen Buxton  4 , Nadia Laack  5 , R Lor Randall  6 , Helen X Chen  7 , Nita L Seibel  7 , Matthew Boron  7 , Stephanie Terezakis  8 , Christine Hill-Kayser  9 , Andrea Hayes  10 , Joel M Reid  11 , Lisa Teot  12 , Dinesh Rakheja  13 , Richard Womer  14 , Carola Arndt  15 , Stephen L Lessnick  16   17 , Brian D Crompton  1   18 , E Anders Kolb  19 , Heike Daldrup-Link  19 , Eric Eutsler  20 , Damon R Reed  21 , Katherine A Janeway  1 , Richard G Gorlick  22
Affiliations
Clinical Trial

Randomized Phase III Trial of Ganitumab With Interval-Compressed Chemotherapy for Patients With Newly Diagnosed Metastatic Ewing Sarcoma: A Report From the Children's Oncology Group

Steven G DuBois et al. J Clin Oncol. .

Abstract

Purpose: Monoclonal antibodies directed against insulin-like growth factor-1 receptor (IGF-1R) have shown activity in patients with relapsed Ewing sarcoma. The primary objective of Children's Oncology Group trial AEWS1221 was to determine if the addition of the IGF-1R monoclonal antibody ganitumab to interval-compressed chemotherapy improves event-free survival (EFS) in patients with newly diagnosed metastatic Ewing sarcoma.

Methods: Patients were randomly assigned 1:1 at enrollment to standard arm (interval-compressed vincristine/doxorubicin/cyclophosphamide alternating once every 2 weeks with ifosfamide/etoposide = VDC/IE) or to experimental arm (VDC/IE with ganitumab at cycle starts and as monotherapy once every 3 weeks for 6 months after conventional therapy). A planned sample size of 300 patients was projected to provide 81% power to detect an EFS hazard ratio of 0.67 or smaller for the experimental arm compared with the standard arm with a one-sided α of .025.

Results: Two hundred ninety-eight eligible patients enrolled (148 in standard arm; 150 in experimental arm). The 3-year EFS estimates were 37.4% (95% CI, 29.3 to 45.5) for the standard arm and 39.1% (95% CI, 31.3 to 46.7) for the experimental arm (stratified EFS-event hazard ratio for experimental arm 1.00; 95% CI, 0.76 to 1.33; 1-sided, P = .50). The 3-year overall survival estimates were 59.5% (95% CI, 50.8 to 67.3) for the standard arm and 56.7% (95% CI, 48.3 to 64.2) for the experimental arm. More cases of pneumonitis after radiation involving thoracic fields and nominally higher rates of febrile neutropenia and ALT elevation were reported on the experimental arm.

Conclusion: Ganitumab added to interval-compressed chemotherapy did not significantly reduce the risk of EFS event in patients with newly diagnosed metastatic Ewing sarcoma, with outcomes similar to prior trials without IGF-1R inhibition or interval compression. The addition of ganitumab may be associated with increased toxicity.

Trial registration: ClinicalTrials.gov NCT02306161.

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Conflict of interest statement

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.

Open Payments is a public database containing information reported by companies about payments made to US-licensed physicians (Open Payments).

Richard G. Gorlick

Research Funding: Eisai (Inst)

No other potential conflicts of interest were reported.

Figures

FIG 1.
FIG 1.
Study schema.
FIG 2.
FIG 2.
CONSORT diagram of patient enrollment and eligibility. aRound cell sarcoma (n = 2); desmoplastic small round cell tumor; NUT carcinoma; BCOR-rearranged sarcoma; bMesenchymal chondrosarcoma; rhabdomyosarcoma; lymphoblastic lymphoma; cWD, withdrawal of consent for any further data submission.
FIG 3.
FIG 3.
Kaplan-Meier curves of (A) EFS and (B) OS from time of random assignment according to randomized arm. EFS, event-free survival; OS, overall survival.
See this image and copyright information in PMC

Comment in

References

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