A combination of targeted therapies may be effective against relapsed or recurrent Ewing’s sarcoma or desmoplastic small-round-cell tumours, according to results of a phase I trial presented at the AACR Annual Meeting 2012, and published simultaneously in Clinical Cancer Research, a journal of the American Association for Cancer Research.
“Ewing’s sarcoma (EWS) is the second most common bone malignancy striking children, adolescents and young adults in the prime of their lives,” said lead researcher Aung Naing, M.D., assistant professor in the department of investigational cancer therapeutics in the division of cancer medicine at The University of Texas MD Anderson Cancer Center in Houston, Texas.
“More treatment options are needed for this disease, because relapse of the disease is quite frequent.
“When tested in the treatment of the EWS family of tumours, single-agent insulin growth factor-1 receptor (IGF-1R) inhibitors and the mTOR inhibitors given as monotherapy have produced variable outcomes.”
The researchers evaluated a subset of 20 patients, including 17 with EWS and three with desmoplastic small-round-cell tumours (DSRCT), who were treated as part of an expansion cohort from a phase I study of an IGF-1R inhibitor, cixutumumab, and the mTOR inhibitor temsirolimus.
All patients had been pretreated heavily before enrolling in the study.
Researchers assigned patients to four-week cycles of 6 mg/kg cixutumumab and 25 mg to 37.5 mg of temsirolimus.
At a median follow-up of 8.9 months, they observed prolonged stable disease lasting more than six months and two complete responses in 29 percent of the patients with EWS. Notably, in one patient who had previously demonstrated a marked clinical response to a different IGF-1R targeted antibody before acquiring resistance, combining IGF-1R inhibition and mTOR inhibition induced a complete response, which provides strong evidence for synergy between mTOR and IGF-1R antagonists.
Four responders developed grade 3 mucositis, myelosuppression or hyperglycemia, which were treated with supportive therapy.
“This study demonstrated early evidence that this combination can be considered for patients with relapsed and recurrent diseases,” Naing said. “Further studies in larger numbers of patients with EWS and DSRCT as well as additional investigation into underlying resistance mechanisms in individual patients are needed.”