Leuprorelin combined with letrozole with/without everolimus in ovarian-suppressed premenopausal women with hormone receptor-positive, HER2-negative metastatic breast cancer: The LEO study.

Abstract

PURPOSE:

In the randomised phase II LEO trial, we investigated the effect of adding everolimus (EVE) to letrozole (LET) in ovarian-suppressed premenopausal women with hormone receptor-positive (HR+), HER2-negative (HER2-) recurrent/metastatic breast cancer.

METHODS:

Patients with progression or prior exposure to tamoxifen with or without gonadotropin-releasing hormone agonists, either sequentially or concurrently, in adjuvant or metastatic setting were randomly assigned (2:1) to the EVE arm (leuprorelin + LET + EVE) or the LET arm (leuprorelin + LET) until disease progression or unacceptable toxicity. The primary end-point was progression-free survival (PFS). Secondary end-points included overall survival (OS), objective response rate (ORR), clinical benefit rate (CBR) and safety.

RESULTS:

Between January 2014 and October 2018, 137 patients were enrolled (median age, 44 years [range, 24-56]). Of them, 75% had endocrine-sensitive disease, and 61% had visceral metastasis. With the median follow-up of 32.4 months, the median PFS was 18.1 months in the EVE arm and 13.8 months in the LET arm (HR 0.73, P = 0.137). Among patients with visceral metastases, the median PFS was significantly longer in the EVE arm (16.4 versus 9.5 months, P = 0.048). The median OS was not reached in both arms. The CBR was significantly higher in the EVE arm (83% versus 62%, P = 0.010). The ORR was similar between the two arms. The most common grade 3/4 adverse events in the EVE arm were neutropenia, alanine aminotransferase elevation and anaemia.

CONCLUSIONS:

EVE plus LET with ovarian-suppression resulted in longer PFS in tamoxifen-exposed HR+, HER2- metastatic breast cancer patients with visceral metastasis.

• Authors: Jae Ho Jeong, Jeong Eun Kim, Jin-Hee Ahn, Kyung Hae Jung, Su-Jin Koh, Jaekyung Cheon, Joohyuk Sohn, Gun Min Kim, Keun Seok Lee, Sung Hoon Sim, In Hae Park, Sung-Bae Kim
• Journal: European journal of cancer (Oxford, England : 1990) (Eur J Cancer) Vol. 144 Pg. 341-350 (02 2021) ISSN: 1879-0852 [Electronic] England
• PMID: 33388491 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2020 Elsevier Ltd. All rights reserved.

Chemical References

• Receptors, Estrogen
• Receptors, Progesterone
• Tamoxifen
• Gonadotropin-Releasing Hormone
• Letrozole
• Everolimus
• Receptor, ErbB-2
• Leuprolide

Topics

• Adult
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Breast Neoplasms (drug therapy, metabolism, pathology)
• Everolimus (administration & dosage)
• Female
• Follow-Up Studies
• Gonadotropin-Releasing Hormone (agonists)
• Humans
• Letrozole (administration & dosage)
• Leuprolide (administration & dosage)
• Middle Aged
• Neoplasm Metastasis
• Neoplasm Recurrence, Local (drug therapy, metabolism, pathology)
• Premenopause
• Primary Ovarian Insufficiency (drug therapy, pathology)
• Prognosis
• Receptor, ErbB-2 (metabolism)
• Receptors, Estrogen (metabolism)
• Receptors, Progesterone (metabolism)
• Survival Rate
• Tamoxifen (administration & dosage)
• Young Adult