Temsirolimus combination improved event-free survival in rhabdomyosarcoma
June 1st 2014
“Children and adolescents who are diagnosed with rhabdomyosarcoma do very poorly following relapse, with a median survival of less than 1 year and long-term survival [of] less than 20%,” Leo Mascarenhas, MD, MS, section head of oncology and director of the Clinical Trials Office of the Children’s Center for Cancer and Blood Diseases at Children’s Hospital Los Angeles, said during a presentation.
The study included 87 patients aged younger than 30 years with biopsy-proven rhabdomyosarcoma whom were given an unfavorable prognosis at first relapse or progression. Patients were randomly assigned to one of two treatment arms administered every 3 weeks for a total of 12 cycles. Regimen A (n=44 patients) included 25 mg/m2 vinorelbine IV on days 1 and 8, 1.2 gms/m2 cyclophosphamide IV on day 1 plus 15 mg bevacizumab IV on day 1. Regimen B (n=43) included vinorelbine and cyclophosphamide identical to regimen A plus 15 mg/m2 temsirolimus IV on days 1, 8 and 15. EFS at 6 months served as the primary outcome measure.
Interim analysis would be conducted when 30%, 50% and 75% of the expected events transpired.
The trial was suspended after the second interim analysis due to 46 events that occurred among the first 68 patients treated with adequate follow-up data, according to Mascarenhas.
Data favored the regimen that included temsirolimus. The O’Brien Flemming boundary corresponded to a 2-sided P-value of .0582 and an observed 2-sided P-value of .0031. When compared with 6-month EFS of 50% (95% CI, 36-66) with regimen A, the 6-month EFS was 65% with regimen B (95% CI, 44-79). In addition, the response rate for regimen A was 27.5% vs. 47.4% with regimen B (P=.22). The rate for progressive disease was 28% with regimen A vs. 10% with regimen B.
However, according to Mascarenhas, there was no significant difference in OS between the two regimens at 2 years.
While oral mucositis and hypertriglyceridemia were observed in the regimen B arm only, febrile neutropenia was the most common adverse event observed in both arms.
“To the best of my knowledge, this is the first positive clinical trial conducted in patients with rhabdomyosarcoma. Temsirolimus has been selected by the Children’s Oncology Group for further investigation in newly diagnosed patients with intermediate risk rhabdomyosarcoma,” he said.
For more information:Mascarenhas L. Abstract #10003. Presented at: ASCO Annual Meeting; May 30-June 3, 2014; Chicago.Disclosure: The researchers report no relevant financial disclosures.