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Ridaforolimus reduced mortality, delayed tumor progression in metastatic sarcoma
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Treatment with the rapamycin inhibitor ridaforolimus decreased the risk for mortality by 28% and delayed tumor progression in patients with metastatic sarcoma who previously benefitted from chemotherapy, according to results of a phase 3 study.
Many patients with metastatic soft tissue and bone sarcomas have rapid disease progression and poor OS, despite treatment with chemotherapy.
George D. Demetri
George D. Demetri, MD, director of the Center for Sarcoma and Bone Oncology and senior vice president for experimental therapeutics at Dana-Farber Cancer Institute in Boston, and colleagues conducted the current investigation to assess the effect of ridaforolimus (Taltorvic, Merck) on controlling advanced soft tissue or bone sarcomas.
The analysis included 702 patients who achieved stable disease with prior chemotherapy.
Patients were randomly assigned to 40 mg ridaforolimus or placebo once-daily for 5 days per week. PFS served as the primary outcome measure. Secondary outcome measures were OS, best target lesion response and safety.
Approximately 10% of patients had bone sarcomas and 90% had soft tissue sarcomas. About 73% had high-grade tumors and 5% had low-grade tumors. More than 60% of patients had lung metastases.
Researchers reported longer PFS (17.7 weeks vs. 14.6 weeks; HR=0.72; 95% CI, 0.61-0.85) and OS (90.6 weeks vs. 85.3 weeks; HR=0.93; 95% CI, 0.78-1.12) among patients assigned to ridaforolimus.
Ridaforolimus induced a mean 1.3% decrease in target lesion size compared with a 10.3% increase among those assigned to placebo (P=.001).
Toxicities were observed with ridaforolimus, as expected with mTOR inhibition, researchers said.
Grade 3 or higher adverse events were more common with ridaforolimus (64.1% vs. 25.6%). They included fatigue, hyperglycemia, infections, noninfectious pneumonitis, rash, stomatitis and thrombocytopenia.
“To our knowledge, this is the first study demonstrating a statistically significant, although clinically small, impact of maintenance treatment on tumor progression in patients with sarcomas,” Demetri and colleagues wrote. “Future studies will build on these results in an effort to improve the outcomes of this rapidly progressive life-threatening disease.”
Disclosure: See the study for a full list of financial disclosures.
Perspective
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Joseph R. Bertino, MD
This is by no means a home run. The benefit was marginal, but the large size of the study suggests it is significant. Combinations with doxorubicin and/or ifosfamide will be of interest, but this is not a non-toxic drug.
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