Overall Survival and Exploratory Biomarker Analyses of Abemaciclib plus Trastuzumab with or without Fulvestrant versus Trastuzumab plus Chemotherapy in HR+, HER2+ Metastatic Breast Cancer Patients

Tolaney, SM; Goel, S; Nadal, J; Denys, H; Borrego, MR; Litchfield, LM; Liu, J; Appiah, AK; Chen, Y; Andr&#233;, F

Author(s): Tolaney, SM; Goel, S; Nadal, J; Denys, H; Borrego, MR; Litchfield, LM; Liu, J; Appiah, AK; Chen, Y; André, F;
Details: Publication Year 2024-01-05,Volume 30,Issue #1,Page 39-49
Journal Title: Clinical Cancer Research
Publication Type: Research article
Abstract: PURPOSE: The monarcHER trial has shown that abemaciclib, a cyclin-dependent kinase 4 and 6 inhibitor, combined with fulvestrant and trastuzumab, improves progression-free survival (PFS) in hormone receptor-positive (HR+), HER2-positive (HER2+) advanced breast cancer (ABC) compared with standard-of-care (SOC) chemotherapy combined with trastuzumab. We report the final overall survival (OS) analysis, updated safety and efficacy data, and exploratory biomarker results from monarcHER. PATIENTS AND METHODS: monarcHER (NCT02675231), a randomized, multicenter, open-label, phase II trial, enrolled 237 patients across Arm A (abemaciclib, trastuzumab, fulvestrant), Arm B (abemaciclib, trastuzumab), and Arm C (SOC chemotherapy, trastuzumab). Following the statistical plan, OS and PFS were estimated in all arms. RNA sequencing (RNA-seq) was performed on archival tissue. RESULTS: Median OS was 31.1 months in Arm A, 29.2 months in Arm B, and 20.7 months in Arm C [A vs. C: HR, 0.71; 95% confidence interval (CI), 0.48-1.05; nominal two-sided P value 0.086; B vs. C: HR 0.83 (95% CI, 0.57-1.23); nominal two-sided P value 0.365]. Updated PFS and safety findings were consistent with previous results. The most frequently reported treatment-emergent adverse events included diarrhea, fatigue, nausea, neutrophil count decrease, and anemia. In exploratory RNA-seq analyses, Luminal subtypes were associated with longer PFS [8.6 vs. 5.4 months (HR, 0.54; 95% CI, 0.38-0.79)] and OS [31.7 vs. 19.7 months (HR, 0.68; 95% CI, 0.46-1.00)] compared with non-Luminal. CONCLUSIONS: In this phase II trial, abemaciclib + trastuzumab ± fulvestrant numerically improved median OS in women with HR+, HER2+ ABC compared with SOC chemotherapy + trastuzumab.
Publisher: American Association for Cancer Research
Keywords: Humans; Female; Trastuzumab/adverse effects; *Breast Neoplasms/drug therapy/genetics/pathology; Fulvestrant/therapeutic use; Receptor, ErbB-2/genetics/therapeutic use; Antineoplastic Combined Chemotherapy Protocols/adverse effects
Department(s): Medical Oncology
Publisher's Version: https://doi.org/10.1158/1078-0432.Ccr-23-1209
Open Access at Publisher's Site: https://doi.org/10.1158/1078-0432.Ccr-23-1209
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2024-02-22 12:10:32

Last Modified: 2024-02-22 12:19:10