Oral ridaforolimus plus trastuzumab for patients with HER2+ trastuzumab-refractory metastatic breast cancer
Jazyk angličtina Země Spojené státy americké Médium print-electronic
Typ dokumentu klinické zkoušky, fáze II, časopisecké články, multicentrická studie
PubMed
25239224
DOI
10.1016/j.clbc.2014.07.008
PII: S1526-8209(14)00163-3
Knihovny.cz E-zdroje
- Klíčová slova
- Breast cancer, HER2, Ridaforolimus, Trastuzumab, mTOR inhibitor,
- MeSH
- analýza přežití MeSH
- aplikace orální MeSH
- chemorezistence účinky léků MeSH
- dospělí MeSH
- duktální karcinom prsu farmakoterapie mortalita patologie MeSH
- humanizované monoklonální protilátky aplikace a dávkování škodlivé účinky MeSH
- lidé středního věku MeSH
- lidé MeSH
- metastázy nádorů MeSH
- nádory prsu farmakoterapie mortalita patologie MeSH
- protokoly protinádorové kombinované chemoterapie aplikace a dávkování škodlivé účinky MeSH
- receptor erbB-2 metabolismus MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- sirolimus aplikace a dávkování škodlivé účinky analogy a deriváty MeSH
- trastuzumab MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky, fáze II MeSH
- multicentrická studie MeSH
- Názvy látek
- ERBB2 protein, human MeSH Prohlížeč
- humanizované monoklonální protilátky MeSH
- receptor erbB-2 MeSH
- ridaforolimus MeSH Prohlížeč
- 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
Citace poskytuje Crossref.org
ClinicalTrials.gov
NCT00736970
