Abemaciclib plus a nonsteroidal aromatase inhibitor as initial therapy for HR+, HER2- advanced breast cancer: Final overall survival results of MONARCH 3.

CDK4/6 inhibitor HR-positive/HER2-negative abemaciclib advanced breast cancer first-line therapy overall survival

Journal

Annals of oncology : official journal of the European Society for Medical Oncology
ISSN: 1569-8041
Titre abrégé: Ann Oncol
Pays: England
ID NLM: 9007735

Informations de publication

Date de publication:
08 May 2024
Historique:
received: 06 03 2024
revised: 29 04 2024
accepted: 30 04 2024
medline: 11 5 2024
pubmed: 11 5 2024
entrez: 10 5 2024
Statut: aheadofprint

Résumé

In MONARCH 2, the addition of abemaciclib to fulvestrant significantly improved both progression-free survival (PFS) and overall survival (OS) in patients with HR+, HER2- advanced breast cancer (ABC) with disease progression on prior endocrine therapy (ET). In MONARCH 3, the addition of abemaciclib to a nonsteroidal aromatase inhibitor (NSAI) as initial therapy for HR+, HER2- ABC significantly improved PFS. Here, we present the prespecified final OS results for MONARCH 3. MONARCH 3 is a randomized, double-blind, phase 3 study of abemaciclib plus NSAI (anastrozole or letrozole) versus placebo plus NSAI in postmenopausal women with HR+, HER2- ABC without prior systemic therapy in the advanced setting. The primary objective was investigator-assessed PFS; OS was a gated secondary endpoint, and chemotherapy-free survival (CFS) was an exploratory endpoint. A total of 493 women were randomized 2:1 to receive abemaciclib plus NSAI (n = 328) or placebo plus NSAI (n = 165). After a median follow-up of 8.1 years, there were 198 OS events (60.4%) in the abemaciclib arm and 116 (70.3%) in the placebo arm (hazard ratio, 0.804; 95% confidence interval [CI], 0.637-1.015; P = 0.0664, non-significant). Median OS was 66.8 versus 53.7 months for abemaciclib versus placebo. In the subgroup with visceral disease (sVD), there were 113 OS events (65.3%) in the abemaciclib arm and 65 (72.2%) in the placebo arm (hazard ratio, 0.758; 95% CI, 0.558-1.030; P = 0.0757, non-significant). Median OS was 63.7 months versus 48.8 months for abemaciclib versus placebo. The previously demonstrated PFS benefit was sustained, and CFS numerically improved with the addition of abemaciclib. No new safety signals were observed. Abemaciclib combined with an NSAI resulted in clinically meaningful improvement in median OS (ITT: 13.1 months; sVD: 14.9 months) in patients with HR+ HER2- ABC; however, statistical significance was not reached.

Sections du résumé

BACKGROUND BACKGROUND
In MONARCH 2, the addition of abemaciclib to fulvestrant significantly improved both progression-free survival (PFS) and overall survival (OS) in patients with HR+, HER2- advanced breast cancer (ABC) with disease progression on prior endocrine therapy (ET). In MONARCH 3, the addition of abemaciclib to a nonsteroidal aromatase inhibitor (NSAI) as initial therapy for HR+, HER2- ABC significantly improved PFS. Here, we present the prespecified final OS results for MONARCH 3.
PATIENTS AND METHODS METHODS
MONARCH 3 is a randomized, double-blind, phase 3 study of abemaciclib plus NSAI (anastrozole or letrozole) versus placebo plus NSAI in postmenopausal women with HR+, HER2- ABC without prior systemic therapy in the advanced setting. The primary objective was investigator-assessed PFS; OS was a gated secondary endpoint, and chemotherapy-free survival (CFS) was an exploratory endpoint.
RESULTS RESULTS
A total of 493 women were randomized 2:1 to receive abemaciclib plus NSAI (n = 328) or placebo plus NSAI (n = 165). After a median follow-up of 8.1 years, there were 198 OS events (60.4%) in the abemaciclib arm and 116 (70.3%) in the placebo arm (hazard ratio, 0.804; 95% confidence interval [CI], 0.637-1.015; P = 0.0664, non-significant). Median OS was 66.8 versus 53.7 months for abemaciclib versus placebo. In the subgroup with visceral disease (sVD), there were 113 OS events (65.3%) in the abemaciclib arm and 65 (72.2%) in the placebo arm (hazard ratio, 0.758; 95% CI, 0.558-1.030; P = 0.0757, non-significant). Median OS was 63.7 months versus 48.8 months for abemaciclib versus placebo. The previously demonstrated PFS benefit was sustained, and CFS numerically improved with the addition of abemaciclib. No new safety signals were observed.
CONCLUSION CONCLUSIONS
Abemaciclib combined with an NSAI resulted in clinically meaningful improvement in median OS (ITT: 13.1 months; sVD: 14.9 months) in patients with HR+ HER2- ABC; however, statistical significance was not reached.

Identifiants

pubmed: 38729566
pii: S0923-7534(24)00139-X
doi: 10.1016/j.annonc.2024.04.013
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

Copyright © 2024. Published by Elsevier Ltd.

Auteurs

M P Goetz (MP)

Department of Oncology, Mayo Clinic, Rochester, MN, USA. Electronic address: goetz.matthew@mayo.edu.

M Toi (M)

Kyoto University, Kyoto, Japan.

J Huober (J)

Breast Center Cantonal Hospital St. Gallen, Switzerland and University of Ulm, Ulm, Germany.

J Sohn (J)

Yonsei Cancer Center, Seoul, Korea.

O Trédan (O)

Centre Léon Bérard, Lyon, France.

I H Park (IH)

National Cancer Center, Goyang-si, Korea.

M Campone (M)

Institut de Cancérologie de l'Ouest, Angers, France.

S-C Chen (SC)

Chang Gung University Medical College, Taipei, Taiwan.

L M Manso (LM)

Hospital Universitario 12 de Octubre, Madrid, Spain.

S Paluch-Shimon (S)

Hadassah University Hospital & Faculty of Medicine Hebrew University, Jerusalem, Israel.

O C Freedman (OC)

Durham Regional Cancer Center, Ontario, Canada.

J O'Shaughnessy (J)

Baylor University Medical Center, Texas Oncology, US Oncology, Dallas, TX, USA.

X Pivot (X)

Centre Paul Strauss, INSERM 110, Strasbourg, France.

S M Tolaney (SM)

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.

S Hurvitz (S)

Department of Medicine, UW Medicine, Fred Hutchinson Cancer Center, Seattle, WA, USA.

A Llombart-Cussac (A)

Hospital Arnau de Vilanova, FISABIO, Valencia, Spain.

V André (V)

Eli Lilly, Indianapolis, IN, USA.

A Saha (A)

Eli Lilly, Indianapolis, IN, USA.

G van Hal (G)

Eli Lilly, Indianapolis, IN, USA.

A Shahir (A)

Eli Lilly, Indianapolis, IN, USA.

H Iwata (H)

Department of Breast Oncology, Aichi Cancer Center Hospital, Nagoya, Japan.

S R D Johnston (SRD)

Breast Unit, The Royal Marsden NHS Foundation Trust, London, UK.

Classifications MeSH