Loading...
VERONICA: randomized phase 2 study of fulvestrant and venetoclax in er-positive metastatic breast cancer Post-CDK4/6 inhibitors - efficacy, safety, biomarker results
Lindeman, G. J. Fernando, T. M. Bowen, R. Jerzak, K. J. Song, X. Decker, T. Boyle, F. McCune, S. Armstrong, Anne C Shannon, C.
Lindeman, G. J.
Fernando, T. M.
Bowen, R.
Jerzak, K. J.
Song, X.
Decker, T.
Boyle, F.
McCune, S.
Armstrong, Anne C
Shannon, C.
Citations
Altmetric:
Abstract
Purpose: Despite promising activity in hematopoietic malignancies, efficacy of the B-cell lymphoma 2 (BCL) inhibitor venetoclax in solid tumors is unknown. We report the prespecified VERONICA primary results, a randomized phase 2 clinical trial evaluating venetoclax and fulvestrant in estrogen receptor (ER)-positive, HER2-negative metastatic breast cancer, post-cyclin-dependent kinase (CDK) 4/6 inhibitor progression.
Patients and methods: Pre-/postmenopausal females {greater than or equal to}18 years were randomized 1:1 to venetoclax (800 mg oral daily) plus fulvestrant (500 mg intramuscular; Cycle 1: Days 1 and 15; subsequent 28-day cycles: Day 1) or fulvestrant alone. The primary endpoint was clinical benefit rate (CBR); secondary endpoints: progression-free survival (PFS), overall survival, and safety. Exploratory biomarker analyses included BCL2 and BCL extra-large (BCLXL) tumor expression, and PIK3CA ctDNA mutational status.
Results: At primary analysis (cutoff: August 5, 2020; n = 103), venetoclax did not significantly improve CBR (venetoclax plus fulvestrant: 11.8% [n = 6/51; 95% confidence interval (CI): 4.44-23.87]; fulvestrant: 13.7% [7/51; 5.70-26.26]; risk difference -1.96% [95% CI: -16.86-12.94]). Median PFS was 2.69 months (95% CI: 1.94-3.71) with venetoclax plus fulvestrant versus 1.94 months (1.84-3.55) with fulvestrant (stratified hazard ratio 0.94 [95% CI: 0.61-1.45]; P = 0.7853). Overall survival data were not mature. A non-significant improvement of CBR and PFS was observed in patients whose tumors had strong BCL2 expression (immunohistochemistry 3+), a BCL2/BCLXL Histoscore ratio {greater than or equal to}1, or PIK3CA-wildtype status.
Conclusions: Our findings do not indicate clinical utility for venetoclax plus fulvestrant in endocrine therapy-resistant, CDK4/6 inhibitor-refractory metastatic breast tumors, but suggest possible increased dependence on BCLXL in this setting.
Description
Date
2022
Publisher
Collections
Files
Loading...
35583555.pdf
Adobe PDF, 2.1 MB
Keywords
Type
Article
Citation
Lindeman GJ, Fernando TM, Bowen R, Jerzak KJ, Song X, Decker T, et al. VERONICA: Randomized Phase II Study of Fulvestrant and Venetoclax in ER-Positive Metastatic Breast Cancer Post-CDK4/6 Inhibitors – Efficacy, Safety, and Biomarker Results. Clinical Cancer Research. American Association for Cancer Research (AACR); 2022. p. OF1–12.