Journal article
Randomized Phase II Trial of Bevacizumab or Temsirolimus in Combination With Chemotherapy for First Relapse Rhabdomyosarcoma: A Report From the Children's Oncology Group
Journal of clinical oncology, Vol.37(31), pp.2866-2874
11/01/2019
DOI: 10.1200/JCO.19.00576
PMCID: PMC6823886
PMID: 31513481
Abstract
PURPOSE The primary aim of this clinical trial was to prioritize bevacizumab or temsirolimus for additional investigation in rhabdomyosarcoma (RMS) when administered in combination with cytotoxic chemotherapy to patients with RMS in first relapse with unfavorable prognosis.
PATIENTS AND METHODS Patients were randomly assigned to receive bevacizumab on day 1 or temsirolimus on days 1, 8, and 15 of each 21-day treatment cycle, together with vinorelbine on days 1 and 8, and cyclophosphamide on day 1 for a maximum of 12 cycles. Local tumor control with surgery and/or radiation therapy was permitted after 6 weeks of treatment. The primary end point was event-free survival (EFS). Radiographic response was assessed at 6 weeks. The study had a phase II selection that was design to detect a 15% difference between the two regimens (alpha = .2; 1-beta = 0.8; two sided test).
RESULTS Eighty-seven of 100 planned patients were enrolled when the trial was closed after the second interim analysis after 46 events occurred in 68 patients with sufficient follow-up. The O'Brien Fleming boundary at this analysis corresponded to a two-sided P value of .058 with an observed two-sided P value of .003 favoring temsirolimus. The 6-month EFS for the bevacizumab arm was 54.6% (95% CI, 39.8% to 69.3%) and 69.1% (95% CI, 55.1% to 83%) for the temsirolimus arm. Objective response rates were 28% (95% CI, 13.7% to 41.3%) and 47% (95% CI, 31.5% to 63.2%) for the bevacizumab and temsirolimus arms, respectively (P = .12) and, 28% of patients on bevacizumab and 11% on temsirolimus had progressive disease at 6 weeks.
CONCLUSION Patients who received temsirolimus had a superior EFS compared with bevacizumab. Temsirolimus has been selected for additional investigation in newly diagnosed patients with intermediate-risk RMS.
Details
- Title: Subtitle
- Randomized Phase II Trial of Bevacizumab or Temsirolimus in Combination With Chemotherapy for First Relapse Rhabdomyosarcoma: A Report From the Children's Oncology Group
- Creators
- Leo Mascarenhas - Children's Hospital of Los AngelesYueh-Yun Chi - University of FloridaPooja Hingorani - Phoenix Children's HospitalJames R. Anderson - MSDElizabeth R. Lyden - University of Nebraska at OmahaDavid A. Rodeberg - East Carolina UniversityDaniel J. Indelicato - University of North FloridaSimon C. Kao - Roy J. and Lucille A. Carver College of MedicineRoshni Dasgupta - Cincinnati Children's Hospital Medical CenterSheri L. Spunt - Stanford UniversityWilliam H. Meyer - University of Oklahoma Health Sciences CenterDouglas S. Hawkins - University of Washington
- Resource Type
- Journal article
- Publication Details
- Journal of clinical oncology, Vol.37(31), pp.2866-2874
- Publisher
- Amer Soc Clinical Oncology
- DOI
- 10.1200/JCO.19.00576
- PMID
- 31513481
- PMCID
- PMC6823886
- ISSN
- 0732-183X
- eISSN
- 1527-7755
- Number of pages
- 10
- Grant note
- St Baldrick's Foundation U10CA180886 / NATIONAL CANCER INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) U10-CA180886; U10-CA180899; U10-CA098543; U10-CA098413 / National Cancer Institute, Children's Oncology Group
- Language
- English
- Date published
- 11/01/2019
- Academic Unit
- Radiology; Stead Family Department of Pediatrics
- Record Identifier
- 9984318805102771
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