Adding Dual mTOR Inhibitor to Fulvestrant Therapy Does Not Improve PFS in Breast Cancer
Patients were randomly assigned to receive fulvestrant, fulvestrant plus continuous daily vistusertib, fulvestrant plus intermittent vistusertib, or fulvestrant plus everolimus.
|The following article features coverage from the San Antonio Breast Cancer Symposium (SABCS) 2017 meeting. Click here to read more of Cancer Therapy Advisor's conference coverage.|
Adding vistusertib (AZD2014) to fulvestrant did not improve progression-free survival (PFS) among women with estrogen receptor–positive (ER+) advanced or metastatic breast cancer, according to findings from the phase 2 MANTA trial presented at the 2017 San Antonio Breast Cancer Symposium.1
The authors noted no PFS benefit after adding the dual mTORC1/2 inhibitor to fulvestrant, though they did find that adding everolimus to fulvestrant improved PFS, reported lead study author Peter Schmid, FRCP, MD, PhD, of Queen Mary University of London in England.
Between April 2014 and October 2016, investigators enrolled 333 postmenopausal women with ER+ breast cancer with disease recurrence while on or within 12 months of completing adjuvant aromatase inhibitor (AI) therapy, or who had disease progression while on or within 1 month of finishing AI treatment for locally advanced or metastatic breast cancer.
Patients were randomly assigned (2:3:3:2) to receive fulvestrant (66 patients), fulvestrant plus continuous daily vistusertib (101 patients), fulvestrant plus intermittent vistusertib (95 patients), or fulvestrant plus everolimus (64 patients). Treatment was continued until disease progression or intolerable toxicity. Participants were stratified by measurable disease and prior endocrine therapy response.
The PFS for fulvestrant plus everolimus was superior to fulvestrant plus continuous vistusertib (12.3 vs 7.6 months; hazard ratio, 0.63; 95% CI: 0.45-0.90; P = .01).
“In the intention-to-treat population, the addition of vistusertib to fulvestrant failed to show a significant PFS improvement over fulvestrant alone,” Dr Schmid noted.
Everolimus plus fulvestrant was associated with a 41% objective response rate compared with 25% for fulvestrant alone and 28.6% and 30.4% for the 2 fulvestrant plus vistusertib study groups, he added.
Read more of Cancer Therapy Advisor's coverage of the San Antonio Breast Cancer Symposium (SABCS) 2017 meeting by visiting the conference page.
- Schmid, P, Zaiss M, Harper-Wynne C, et al. MANTA - a randomized phase II study of fulvestrant in combination with the dual mTOR inhibitor AZD2014 or everolimus or fulvestrant alone in estrogen receptor-positive advanced or metastatic breast cancer. Oral presentation at: San Antonio Breast Cancer Symposium 2017. Dec. 5-8, 2017; San Antonio, TX.