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J Clin Oncol. 2019 Nov 1;37(31):2866-2874. doi: 10.1200/JCO.19.00576. Epub 2019 Sep 12.

Randomized Phase II Trial of Bevacizumab or Temsirolimus in Combination With Chemotherapy for First Relapse Rhabdomyosarcoma: A Report From the Children's Oncology Group.

Author information

1
Children's Hospital Los Angeles and University of Southern California Keck School of Medicine, Los Angeles, CA.
2
University of Florida, Gainesville, FL.
3
Phoenix Children's Hospital, Phoenix, AZ.
4
Merck Research Laboratories: Oncology, North Wales, PA.
5
University of Nebraska College of Medicine, Omaha, NE.
6
East Carolina University, Greenville, NC.
7
University of Florida, Jacksonville, FL.
8
University of Iowa Carver College of Medicine, Iowa City, IA.
9
Cincinnati Children's Hospital Medical Center, Cincinnati, OH.
10
Stanford University School of Medicine, Stanford, CA.
11
University of Oklahoma Health Sciences Center, Oklahoma City, OK.
12
University of Washington, Seattle, WA.

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 (α = .2; 1-β = 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.

PMID:
31513481
PMCID:
PMC6823886
[Available on 2020-11-01]
DOI:
10.1200/JCO.19.00576

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