Abstract
To determine the feasible dose and schedule for everolimus, an oral mTOR inhibitor, combined with vinorelbine and trastuzumab for patients with HER2-overexpressing metastatic breast cancer pretreated with trastuzumab. In this phase Ib multicenter, Bayesian dose-escalation study, 50 patients received everolimus 5 mg/day, 20 mg/week, or 30 mg/week plus vinorelbine (25 mg/m 2 on day 1 and 8 every 3 weeks) and trastuzumab (2 mg/kg weekly). Endpoints included end-of-cycle-1 dose-limiting toxicity (DLT) rate (primary endpoint), safety, relative dose intensity, overall response rate (ORR), and pharmacokinetics. Grade 3/4 neutropenia was the most common end-of-cycle-1 DLT and occurred in 10 of 30 and 4 of 14 patients in the 5 mg/day and 30 mg/week cohorts, respectively. Other end-of-cycle-1 DLTs included single cases of febrile neutropenia, grade 3 stomatitis with concomitant fatigue, grade 2 stomatitis, grade 3 anorexia, and grade 2 acneiform dermatitis, all in the 5-mg/day cohort. Based on the recorded DLTs and global safety, everolimus 5 mg/day and 30 mg/week were chosen as the optimal dose levels for the daily and weekly arms. Forty-seven patients were evaluable for efficacy. ORR was 19.1%, with a disease control rate of 83.0% and median progression-free survival of 30.7 weeks. No drug interaction was observed between everolimus and vinorelbine. Everolimus combined with weekly vinorelbine and trastuzumab generally was well tolerated and had encouraging antitumor activity in heavily pretreated patients with HER2-overexpressing metastatic breast cancer that progressed on trastuzumab (NCT00426530).
| Original language | English |
|---|---|
| Pages (from-to) | 447-455 |
| Number of pages | 9 |
| Journal | Breast Cancer Research and Treatment |
| Volume | 125 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - Jan 2011 |
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Keywords
- Everolimus
- HER2-overexpressing metastatic breast cancer
- mTOR
- Phase I
- Trastuzumab
- Vinorelbine
ASJC Scopus subject areas
- Oncology
- Cancer Research
Cite this
Phase i trial of oral mTOR inhibitor everolimus in combination with trastuzumab and vinorelbine in pre-treated patients with HER2-overexpressing metastatic breast cancer. / Jerusalem, Guy; Fasolo, Angelica; Dieras, Veronique; Cardoso, Fatima; Bergh, Jonas; Vittori, Luc; Zhang, Yufen; Massacesi, Cristian; Sahmoud, Tarek; Gianni, Luca.
In: Breast Cancer Research and Treatment, Vol. 125, No. 2, 01.2011, p. 447-455.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Phase i trial of oral mTOR inhibitor everolimus in combination with trastuzumab and vinorelbine in pre-treated patients with HER2-overexpressing metastatic breast cancer
AU - Jerusalem, Guy
AU - Fasolo, Angelica
AU - Dieras, Veronique
AU - Cardoso, Fatima
AU - Bergh, Jonas
AU - Vittori, Luc
AU - Zhang, Yufen
AU - Massacesi, Cristian
AU - Sahmoud, Tarek
AU - Gianni, Luca
PY - 2011/1
Y1 - 2011/1
N2 - To determine the feasible dose and schedule for everolimus, an oral mTOR inhibitor, combined with vinorelbine and trastuzumab for patients with HER2-overexpressing metastatic breast cancer pretreated with trastuzumab. In this phase Ib multicenter, Bayesian dose-escalation study, 50 patients received everolimus 5 mg/day, 20 mg/week, or 30 mg/week plus vinorelbine (25 mg/m 2 on day 1 and 8 every 3 weeks) and trastuzumab (2 mg/kg weekly). Endpoints included end-of-cycle-1 dose-limiting toxicity (DLT) rate (primary endpoint), safety, relative dose intensity, overall response rate (ORR), and pharmacokinetics. Grade 3/4 neutropenia was the most common end-of-cycle-1 DLT and occurred in 10 of 30 and 4 of 14 patients in the 5 mg/day and 30 mg/week cohorts, respectively. Other end-of-cycle-1 DLTs included single cases of febrile neutropenia, grade 3 stomatitis with concomitant fatigue, grade 2 stomatitis, grade 3 anorexia, and grade 2 acneiform dermatitis, all in the 5-mg/day cohort. Based on the recorded DLTs and global safety, everolimus 5 mg/day and 30 mg/week were chosen as the optimal dose levels for the daily and weekly arms. Forty-seven patients were evaluable for efficacy. ORR was 19.1%, with a disease control rate of 83.0% and median progression-free survival of 30.7 weeks. No drug interaction was observed between everolimus and vinorelbine. Everolimus combined with weekly vinorelbine and trastuzumab generally was well tolerated and had encouraging antitumor activity in heavily pretreated patients with HER2-overexpressing metastatic breast cancer that progressed on trastuzumab (NCT00426530).
AB - To determine the feasible dose and schedule for everolimus, an oral mTOR inhibitor, combined with vinorelbine and trastuzumab for patients with HER2-overexpressing metastatic breast cancer pretreated with trastuzumab. In this phase Ib multicenter, Bayesian dose-escalation study, 50 patients received everolimus 5 mg/day, 20 mg/week, or 30 mg/week plus vinorelbine (25 mg/m 2 on day 1 and 8 every 3 weeks) and trastuzumab (2 mg/kg weekly). Endpoints included end-of-cycle-1 dose-limiting toxicity (DLT) rate (primary endpoint), safety, relative dose intensity, overall response rate (ORR), and pharmacokinetics. Grade 3/4 neutropenia was the most common end-of-cycle-1 DLT and occurred in 10 of 30 and 4 of 14 patients in the 5 mg/day and 30 mg/week cohorts, respectively. Other end-of-cycle-1 DLTs included single cases of febrile neutropenia, grade 3 stomatitis with concomitant fatigue, grade 2 stomatitis, grade 3 anorexia, and grade 2 acneiform dermatitis, all in the 5-mg/day cohort. Based on the recorded DLTs and global safety, everolimus 5 mg/day and 30 mg/week were chosen as the optimal dose levels for the daily and weekly arms. Forty-seven patients were evaluable for efficacy. ORR was 19.1%, with a disease control rate of 83.0% and median progression-free survival of 30.7 weeks. No drug interaction was observed between everolimus and vinorelbine. Everolimus combined with weekly vinorelbine and trastuzumab generally was well tolerated and had encouraging antitumor activity in heavily pretreated patients with HER2-overexpressing metastatic breast cancer that progressed on trastuzumab (NCT00426530).
KW - Everolimus
KW - HER2-overexpressing metastatic breast cancer
KW - mTOR
KW - Phase I
KW - Trastuzumab
KW - Vinorelbine
UR - http://www.scopus.com/inward/record.url?scp=78650967232&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=78650967232&partnerID=8YFLogxK
U2 - 10.1007/s10549-010-1260-x
DO - 10.1007/s10549-010-1260-x
M3 - Article
VL - 125
SP - 447
EP - 455
JO - Breast Cancer Research and Treatment
JF - Breast Cancer Research and Treatment
SN - 0167-6806
IS - 2
ER -