Cancer Treatment Today

Early clinical trials suggested that shows that the addition of Afinitor to chemotherapy with Herceptin can overcome resistance to Herceptin. In 2011, a Phase III clinical trial (BOLERO-2) showed survival without cancer progression was 6.9 months among women treated with both Afinitor and Aromasin, compared with 2.8 months among women treated with Aromasin alone. AFINITOR® is indicated for the treatment of postmenopausal women with advanced hormone receptor-positive, HER2-negative breast cancer (advanced HR+ BC) in combination with exemestane, after failure of treatment with letrozole or anastrozole.

The addition of everolimus (Afinitor) to fulvestrant (Faslodex) doubled progression-free survival in postmenopausal women with hormone receptor–positive, HER2-negative metastatic breast cancer resistant to aromatase inhibitor therapy compared with fulvestrant plus placebo, according to the randomized, controlled phase II PrECOG 0102 trial. These results were presented at the 2016 San Antonio Breast Cancer Symposium.The only actually published clinical trial, not the strict, is by Massarweh a WEHE tall. She concludes everolimus plus fulvestrant is effective after AI failure in heavily pretreated metastatic ER-positive breast cancer and has manageable toxicity. Further study of this combination is warranted in randomized studies. Since not all patients experience benefit, and in view of potential toxicities, biomarker examination is critical to help select patients most likely to benefit from this strategy in future studies.

Kornblum NS, Manola J, Klein P, et al: PrECOG 0102: A randomized, double-blind, phase II trial of fulvestrant plus everolimus or placebo in post-menopausal women with hormone receptor-positive, HER2-negative metastatic breast cancer resistant to aromatase inhibitor therapy. 2016 San Antonio Breast Cancer Symposium. Abstract S1-02. Presented December 7, 2016.

Massarweh S, Breast Cancer Res Treat. A phase II study of combined fulvestrant and everolimus in patients with metastatic estrogen receptor (ER)-positive breast cancer after aromatase inhibitor (AI) failure. Breast Cancer Res Treat. 2014 Jan;143(2):325-32. .

Bachelot T, Bourgier C, Cropet C, Ray-Coquard I, Ferrero JM, Freyer G, Abadie-Lacourtoisie S, Eymard JC, Debled M, Spaëth D, Legouffe E, Allouache D, El Kouri C, Pujade-Lauraine E. Randomized phase II trial of everolimus in combination with tamoxifen in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative metastatic breast cancer with prior exposure to aromatase inhibitors: a GINECO study. J Clin Oncol. 2012 Aug 1;30(22):2718-24.
Fasolo, A., et al. Multicenter Phase I Clinical Trial of Daily and Weekly Everolimus (RAD001) in Combination with Vinorelbine and Trastuzumab in Patients with HER-2-Overexpressing in Metastatic Breast Cancer with Prior Resistance to Trastuzumab. Poster presented at SABCS 2008.

Morrow P.K. et al, “Phase I/II trial of everolimus (RAD001) and trastuzumab in patients with trastuzumab-resistant, HER2-overexpressing breast cancer,”Abstract 1014, Journal of Clinical Oncology. Vol. 28, No. 15s, p. 117s.