Combination Targeted Therapy Well Tolerated, Effective for Refractory Ewing’s Sarcoma Tumors
- EWS is the second most common bone malignancy in children and adolescents.
- Combination therapy efficacious against chemotherapy-resistant EWS.
- The combination was safe, with manageable adverse events.
CHICAGO — A combination of targeted therapies may be effective against relapsed or recurrent Ewing’s sarcoma or desmoplastic small-round-cell tumors, according to results of a phase I trial presented at the AACR Annual Meeting 2012, held here March 31 – April 4, 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 tumors, 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 tumors (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.”
Press registration for the AACR Annual Meeting 2012 is free to qualified journalists and public information officers: www.aacr.org/PressRegistration.
About the AACR
Founded in 1907, the American Association for Cancer Research (AACR) is the world’s first and largest professional organization dedicated to advancing cancer research and its mission to prevent and cure cancer. AACR’s membership includes 34,000 laboratory, translational and clinical researchers; population scientists; other health care professionals; and cancer advocates residing in more than 90 countries. The AACR marshals the full spectrum of expertise of the cancer community to accelerate progress in the prevention, biology, diagnosis and treatment of cancer by annually convening more than 20 conferences and educational workshops, the largest of which is the AACR Annual Meeting with more than 18,000 attendees. In addition, the AACR publishes seven peer-reviewed scientific journals and a magazine for cancer survivors, patients and their caregivers. The AACR funds meritorious research directly as well as in cooperation with numerous cancer organizations. As the Scientific Partner of Stand Up To Cancer, the AACR provides expert peer review, grants administration and scientific oversight of individual and team science grants in cancer research that have the potential for patient benefit. The AACR actively communicates with legislators and policymakers about the value of cancer research and related biomedical science in saving lives from cancer.
For more information about the AACR, visit www.AACR.org.
In Chicago, March 31 – April 4: