PMID- 29097108 OWN - NLM STAT- MEDLINE DCOM- 20190320 LR - 20190320 IS - 1938-0666 (Electronic) IS - 1526-8209 (Linking) VI - 18 IP - 2 DP - 2018 Apr TI - Everolimus Plus Letrozole for Treatment of Patients With HR(+), HER2(-) Advanced Breast Cancer Progressing on Endocrine Therapy: An Open-label, Phase II Trial. PG - e197-e203 LID - S1526-8209(17)30180-5 [pii] LID - 10.1016/j.clbc.2017.09.004 [doi] AB - PURPOSE: In the Breast cancer trials of OraL EveROlimus-2 (BOLERO-2) trial, everolimus plus exemestane improved progression-free survival (PFS) in patients with hormone receptor-positive (HR(+)), human epidermal growth factor receptor 2-negative (HER2(-)) advanced breast cancer (ABC) recurring or progressing on/after prior endocrine therapy (ET), suggesting that dual blockade using targeted therapy and ET was an effective treatment option. Here, we investigated the clinical benefit of combining everolimus with different endocrine partner, letrozole, in a similar patient population. METHODS: In this phase II, open-label, single-arm, multicenter trial, postmenopausal women with HR(+), HER2(-) ABC who had recurrence/progression on/after prior ET received everolimus 10 mg daily and letrozole 2.5 mg daily. The primary end point was objective response rate; key secondary end points included disease-control rate, PFS, overall survival, and safety. RESULTS: A total of 72 patients were enrolled and followed-up for a median duration of 11.4 months. Everolimus plus letrozole achieved an overall response rate of 23.3% (95% confidence interval [CI], 13.4%-36.0%). The median PFS was 8.8 months (95% CI, 6.6-11.0 months), and the overall survival was 22.9 months (95% CI, 18.5-28.9 months). Disease-control rate was achieved in 51 (85%) patients. The safety profile was consistent with previously published data: The most frequently reported any grade adverse events (AEs) were fatigue (61.1%), stomatitis (54.2%), and rash (33.4%). The most frequently reported grade 3 AEs were stomatitis and anemia (8.3% each), fatigue and diarrhea (5.6% each), and hyperglycemia (4.2%). Only 1 patient had grade 4 AE of anemia. CONCLUSIONS: Everolimus plus letrozole demonstrated clinical benefit and could be a valid treatment option for postmenopausal women recurring/progressing on prior endocrine therapy. CI - Copyright (c) 2017 Elsevier Inc. All rights reserved. FAU - Safra, Tamar AU - Safra T AD - Head of Onco-Gynecology Service, Department of Oncology, Tel Aviv Sourasky Medical Center, Tel Aviv University, Tel Aviv, Israel; Department of Internal Medicine, Tel Aviv Sourasky Medical Center, Tel Aviv University, Tel Aviv, Israel. Electronic address: safrat@bezeqint.net. FAU - Kaufman, Bella AU - Kaufman B AD - Breast Oncology Institute, Sheba Medical Center, Tel Hashomer, Israel. FAU - Kadouri, Luna AU - Kadouri L AD - Sharett Institute of Oncology, Hadassah Medical Center, Hebrew University, Jerusalem, Israel. FAU - Efrat Ben-Baruch, Noa AU - Efrat Ben-Baruch N AD - Oncology Institute, Kaplan Medical Center, Rehovot, Israel. FAU - Ryvo, Larisa AU - Ryvo L AD - Division of Oncology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel. FAU - Nisenbaum, Bella AU - Nisenbaum B AD - Institute of Oncology, Meir Medical Center, Kfar Saba, Israel. FAU - Evron, Ella AU - Evron E AD - Department of Oncology, Assaf Harofeh Medical Center, Affiliated with Tel Aviv University, Zerifin, Israel. FAU - Yerushalmi, Rinat AU - Yerushalmi R AD - Institute of Oncology, Davidoff Cancer Center, Beilinson Medical Center, Tel Aviv University, Tel Aviv, Israel; Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel. LA - eng PT - Clinical Trial, Phase II PT - Journal Article PT - Multicenter Study PT - Research Support, Non-U.S. Gov't DEP - 20170919 PL - United States TA - Clin Breast Cancer JT - Clinical breast cancer JID - 100898731 RN - 0 (Antineoplastic Agents, Hormonal) RN - 0 (Receptors, Estrogen) RN - 0 (Receptors, Progesterone) RN - 7LKK855W8I (Letrozole) RN - 9HW64Q8G6G (Everolimus) RN - EC 2.7.10.1 (ERBB2 protein, human) RN - EC 2.7.10.1 (Receptor, ErbB-2) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Anemia/chemically induced/epidemiology MH - Antineoplastic Agents, Hormonal/therapeutic use MH - Antineoplastic Combined Chemotherapy Protocols/*therapeutic use MH - Breast/pathology MH - Breast Neoplasms/*drug therapy/mortality/pathology MH - Diarrhea/chemically induced/epidemiology MH - Everolimus/*therapeutic use MH - Exanthema/chemically induced MH - Fatigue/chemically induced/epidemiology MH - Female MH - Follow-Up Studies MH - Humans MH - Kaplan-Meier Estimate MH - Letrozole/*therapeutic use MH - Middle Aged MH - Neoplasm Recurrence, Local/*drug therapy/mortality/pathology MH - Postmenopause MH - Progression-Free Survival MH - Receptor, ErbB-2/metabolism MH - Receptors, Estrogen/metabolism MH - Receptors, Progesterone/metabolism MH - Response Evaluation Criteria in Solid Tumors MH - Stomatitis/chemically induced/epidemiology OTO - NOTNLM OT - Advanced breast cancer OT - Endocrine therapy OT - Everolimus OT - Hormone receptor-positive OT - Letrozole EDAT- 2017/11/04 06:00 MHDA- 2019/03/21 06:00 CRDT- 2017/11/04 06:00 PHST- 2017/03/23 00:00 [received] PHST- 2017/08/16 00:00 [revised] PHST- 2017/09/05 00:00 [accepted] PHST- 2017/11/04 06:00 [pubmed] PHST- 2019/03/21 06:00 [medline] PHST- 2017/11/04 06:00 [entrez] AID - S1526-8209(17)30180-5 [pii] AID - 10.1016/j.clbc.2017.09.004 [doi] PST - ppublish SO - Clin Breast Cancer. 2018 Apr;18(2):e197-e203. doi: 10.1016/j.clbc.2017.09.004. Epub 2017 Sep 19.