Oral ridaforolimus plus trastuzumab for patients with HER2+ trastuzumab-refractory metastatic breast cancer
Language English Country United States Media print-electronic
Document type Clinical Trial, Phase II, Journal Article, Multicenter Study
PubMed
25239224
DOI
10.1016/j.clbc.2014.07.008
PII: S1526-8209(14)00163-3
Knihovny.cz E-resources
- Keywords
- Breast cancer, HER2, Ridaforolimus, Trastuzumab, mTOR inhibitor,
- MeSH
- Survival Analysis MeSH
- Administration, Oral MeSH
- Drug Resistance, Neoplasm drug effects MeSH
- Adult MeSH
- Carcinoma, Ductal, Breast drug therapy mortality pathology MeSH
- Antibodies, Monoclonal, Humanized administration & dosage adverse effects MeSH
- Middle Aged MeSH
- Humans MeSH
- Neoplasm Metastasis MeSH
- Breast Neoplasms drug therapy mortality pathology MeSH
- Antineoplastic Combined Chemotherapy Protocols administration & dosage adverse effects MeSH
- Receptor, ErbB-2 metabolism MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Sirolimus administration & dosage adverse effects analogs & derivatives MeSH
- Trastuzumab MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Clinical Trial, Phase II MeSH
- Multicenter Study MeSH
- Names of Substances
- ERBB2 protein, human MeSH Browser
- Antibodies, Monoclonal, Humanized MeSH
- Receptor, ErbB-2 MeSH
- ridaforolimus MeSH Browser
- Sirolimus MeSH
- Trastuzumab MeSH
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). Ridaforolimus was administered orally (40 mg daily) for 5 d/wk plus weekly trastuzumab. The primary end point was objective response (OR). RESULTS: Thirty-four patients were enrolled (91% had received 1 or 2 previous trastuzumab-based therapies, whereas 9% had received 3 previous therapies). The most common reasons for discontinuation were disease progression (62%) and adverse events (AEs; 24%). Three patients died; 1 because of bowel perforation, which was possibly ridaforolimus related. Partial response was observed in 5 patients (15%). Median duration of response was 19.1 weeks (range, 15.9-80.1 weeks). Fourteen patients (41%) achieved stable disease (SD); 7 patients (21%) maintained SD for ≥ 24 weeks. The clinical benefit response (CBR) rate was 34.3%. Median progression-free survival (PFS) and overall survival (OS) were 5.4 months (range, 0-20.3 months; 95% confidence interval [CI], 2.0-7.4) and 17.7 months (range, 0-25.9 months; 95% CI, 8.8-20.8), respectively. PFS rate at 6 months was 37%. The most common treatment-related AEs were stomatitis (59%), diarrhea (27%), and rash (27%). CONCLUSION: Ridaforolimus-trastuzumab was well tolerated and demonstrated antitumor activity in trastuzumab-resistant HER2(+) MBC.
ARIAD Pharmaceuticals Inc Cambridge MA
Biostatistics and Research Decision Sciences Asia Pacific MSD R and D Co Ltd Beijing China
Département d'oncologie médicale adulte Lyon France
Hematology and Oncology Specialists LLC New Orleans LA
Merck and Co Inc Whitehouse Station NJ
Sarah Cannon Research Institute and Tennessee Oncology PLLC Nashville TN
References provided by Crossref.org
ClinicalTrials.gov
NCT00736970
