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June 1, 2014 (ASCO-2014)
CHICAGO — The addition of temsirolimus to vinorelbine and cyclophosphamide led to increased event-free survival at 6 months and 1 year compared with vinorelbine and cyclophosphamide plus bevacizumab in patients with first relapse rhabdomyosarcoma.

“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.

PERSPECTIVE – Leonard H. Wexler, MD
There are about 400 new cases of rhabdomyosarcoma diagnosed in children younger than 19 years in this country every year. Part of the clinical dilemma in treating this disease is that we look at it as a single disease, but it is not. There have been no net improvements in outcomes for more than 20 years, and local treatment failure remains the dominant risk for most patients. In this study, there was no difference in 2-year survival between the two groups. Based on these results, a ‘with or without temsirolimus’ question will be the basis of the next INT-RISK study. It is not clear that these results are transferable to patients with localized tumors.

Leonard H. Wexler, MD
Pediatric oncologist
Memorial Sloan-Kettering Cancer Center
Disclosures: Wexler reports no relevant financial disclosures.