Oral ridaforolimus plus trastuzumab for patients with HER2+ trastuzumab-refractory metastatic breast cancer.

Background: Although trastuzumab-containing therapies prolong survival in patients with metastatic breast cancer (MBC), most tumors develop trastuzumab resistance, potentially mediated by aberrant phosphatidylinositide 3-kinase (PI3K)/AKT signaling. Ridaforolimus (a mammalian target of rapamycin [mTOR] inhibitor) may overcome trastuzumab resistance by inhibiting PI3K signaling.

Methods: A single-arm, phase IIb trial was conducted to evaluate the efficacy and safety of ridaforolimus-trastuzumab in human epidermal growth factor receptor 2-positive (HER2(+)) trastuzumab-refractory MBC (NCT00736970).

Results of an international randomized phase III trial of the mammalian target of rapamycin inhibitor ridaforolimus versus placebo to control metastatic sarcomas in patients after benefit from prior chemotherapy.

Purpose: Aberrant mammalian target of rapamycin (mTOR) signaling is common in sarcomas and other malignancies. Drug resistance and toxicities often limit benefits of systemic chemotherapy used to treat metastatic sarcomas. This large randomized placebo-controlled phase III trial evaluated the mTOR inhibitor ridaforolimus to assess maintenance of disease control in advanced sarcomas.