Patrick Neven, MD, a gynecologist-oncologist at the University Hospitals Leuven, discusses the association between cell cycle–related genes and outcomes for patients with hormone receptor(HR)–positive/HER2-negative advanced breast cancer treated on the phase 3 MONALEESA-2 (NCT01958021), MONALEESA-3 (NCT02422615), and MONALEESA-7 (NCT02278120) trials.

At the 2022 San Antonio Breast Cancer Symposium, data were presented from a pooled analysis of gene expression using tumor samples from 1139 patients with HR-positive/HER2-negative advanced breast cancer enrolled on the MONALEESA trials that were used to understand how outcomes for these patients may have been related to cell cycle–related genes. Findings showed that progression-free survival (PFS) benefit with ribociclib (Kisqali) plus endocrine therapy was consistent regardless of the CDK4/6 expression ratio or level of expression of CCNE1, CDK2, RB1, combined cell cycle–related genes, E2F gene signatures, RB gene signature, combined DNA-replication genes, or combined proliferation-related genes.

Findings also showed that patients who were treated with the combination of endocrine treatment plus ribociclib did not have tumors that were more aggressive if they were treated through the subsequent agent, Neven explains. Notably, patients treated with the combination were less likely to have chemotherapy as subsequent treatment, Neven notes.

Moreover, the duration of treatment predicted the subsequent treatment for patients in both arms. For example, if patients experienced a shorter PFS, they were more likely to get chemotherapy, Neven says. Conversely, if a patient experienced a longer PFS, they were more likely to get endocrine therapy with or without targeted therapy, Neven continues.

Numerically, patients who were treated with the endocrine therapy plus ribociclib experienced longer durations of treatment with subsequent therapies, unless they received chemotherapy, Neven continues. The group of patients with the longest overall survival (OS) were those who had the combination treatment with ribociclib and endocrine therapy, followed by another CDK4/6 inhibitor or the same CDK4/6 inhibitor, Neven concludes.

Videos

Patrick Neven, MD, discusses the association between cell cycle–related genes and outcomes for patients with hormone receptor–positive/HER2-negative advanced breast cancer treated on the phase 3 MONALEESA-2, MONALEESA-3, and MONALEESA-7 trials. 

Dr. Neven on the Relationship of Cell Cycle Genes and Outcomes in HR+/HER2– Breast Cancer

Data from the following clinical trials are discussed:

GS2-05 oral presentation: Randomized comparision of adjuvant aromatase inhibitor exemestane + ovarian function suppression (OFS) vs tamoxifen + OFS in premenopausal women with hormone receptor-positive early breast cancer: update of the TEXT and SOFT trials

GS3-00: First results from a phase 3 randomized clinical trail of standard adjuvant endocrine therapy +/- chemotherapy in patients with 1-3 positive nodes, hormone receptor-positive and HER2-negative breast cancer with recurrence score < 25: SWOG S1007 (RxPONDER)

GS1-08: CCTGMA.32, a phase 3 randomized double-blind placebo-controlled adjuvant trial of metformin vs placebo in early breast cancer: Results of the primary efficacy analysis (NCT0110143)

GS1-05: Datopotamab deruxtecan in advanced/metastatic HER2 breast cancer: Results from the phase 1 TROPION-PanTumor01 study

Patrick Neven MD, PhD; Sara A. Hurvitz, MD; Kevin Kalinsky, MD, MS; and Aditya Bardia, MD, MPH, share insight on updates in key clinical trials and novel therapies in breast cancer presented at SABCS 2021.

SABCS 2021 Updates in Key Clinical Trials for Breast Cancer

P1-18-16: First-line aromatase inhibitor + palbociclib with randomized switch to fulvestrant [Faslodex] + palbociclib upon detection of circulating 

 mutation in HR+/HER2 metastatic breast cancer patients: Global safety results of PADA-1, a UCBG-GINECO phase 3 trial

PD2-05: Genomic profiling of PAM50-based intrinsic subtypes in HR+/HER2 advanced breast cancer across the MONALEESA studies

PD13-03: Ribociclib [Kisqali], everolimus, exemestane [Aromasin] triplet therapy in HR+/HER2 advanced breast cancer after progression on a CDK4/6 inhibitor: Final efficacy, safety, and biomarker results from TRINITI-1

PD02-04: Molecular plasticity of luminal A breast cancer and response to CDK4/6 inhibition: The biomarker program of the PENELOPE-B trial investigating post-neoadjuvant palbociclib

Sara A. Hurvitz, MD; Aditya Bardia, MD, MPH; Patrick Neven, MD, PhD; and Kevin Kalinsky MD, MS, discuss SABCS 2021 updates on the use of CDK4/6 inhibitors in HR+/HER2 breast cancer.

SABCS 2021 Updates in CDK4/6 Inhibitors in Breast Cancer

P1-17-11: Updated data from AMEERA-1: Phase 1/2 study of amcenestrant (SAR439859), an oral selective estrogen receptor degrader (SERD), combined with palbociclib [Ibrance] in postmenopausal women with ER+/HER2 advanced breast cancer

GS2 -02: Elacestrant, an oral selective estrogen receptor degrader (SERD) vs investigator's choice of endocrine monotherapy for ER+/HER2 advanced/metastatic breast cancer following progression on prior endocrine and CDK4/6 inhibitor therapy: Results of EMERALD phase 3 trial

PD13-08: First-in-human safety and activity of ARV-471, a novel PROTAC estrogen receptor degrader, in ER+/HER2 locally advanced or metastatic breast cancer

Experts in the management of breast cancer review recent data on SERDs (selective estrogen receptor degraders) in ER+/HER2 advanced breast cancer presented at SABCS [San Antonio Breast Cancer Symposium] 2021.

SABCS 2021 Updates in ER+ Breast Cancer

Patrick Neven, MD, Universitair Ziekenhuis Leuven, Belgium, outlines the design of the phase III MONALEESA-3 trial in hormone receptor—positive, HER2-negative advanced breast cancer.

The multicenter, randomized, double-blind trial sought to improve the outcomes of this postmenopausal patients with HR-positive, HER2-negative advanced disease who received either no lines or only 1 prior line of endocrine treatment. The primary end point of the trial was progression-free survival (PFS) and overall survival (OS) served as a secondary end point, says Neven.

In the trial, patients were randomized to receive either ribociclib (Kisqali) in combination with fulvestrant (Faslodex) or fulvestrant plus placebo. Results showed a significant improvement in PFS with ribociclib/fulvestrant compared with fulvestrant/placebo. Furthermore, at a median follow-up of 39.4 months, the ribociclib combination showed a statistically significant prolongation in OS compared with fulvestrant/placebo.

Patrick Neven, MD, outlines the design of the phase III MONALEESA-3 trial in hormone receptor–positive, HER2-negative advanced breast cancer.
 

Patrick Neven, MD, PhD

Articles

Dr. Neven on the Relationship of Cell Cycle Genes and Outcomes in HR+/HER2– Breast Cancer

SABCS 2021 Updates in Key Clinical Trials for Breast Cancer

SABCS 2021 Updates in CDK4/6 Inhibitors in Breast Cancer

SABCS 2021 Updates in ER+ Breast Cancer

Dr. Neven on the Design of the MONALEESA-3 Trial in Advanced Breast Cancer