Supplementary Figure S2 from Breast Cancer Index and Prediction of Extended Aromatase Inhibitor Therapy Benefit in Hormone Receptor-Positive Breast Cancer from the NRG Oncology/NSABP B-42 Trial
posted on 2024-05-01, 07:20authored byEleftherios P. Mamounas, Hanna Bandos, Priya Rastogi, Yi Zhang, Kai Treuner, Peter C. Lucas, Charles E. Geyer, Louis Fehrenbacher, Stephen K. Chia, Adam M. Brufsky, Janice M. Walshe, Gamini S. Soori, Shaker Dakhil, Soonmyung Paik, Sandra M. Swain, Dennis C. Sgroi, Catherine A. Schnabel, Norman Wolmark
Supplemental Figure SF2. Exploratory Kaplan-Meier analysis based on A, any new primary cancer and B, new breast primary
cancer comparing extended letrozole vs placebo in the overall Breast Cancer Index (BCI) NSABP B-42 translational cohort.
Funding
NCI
Korea Health Technology R&D Project
Novartis, which provided letrozole and placebo to all study sites during the course of the study
Biotheranostics Inc
BCRF
History
ARTICLE ABSTRACT
BCI (H/I) has been shown to predict extended endocrine therapy (EET) benefit. We examined BCI (H/I) for EET benefit prediction in NSABP B-42, which evaluated extended letrozole therapy (ELT) in patients with hormone receptor-positive breast cancer after 5 years of ET.
A stratified Cox model was used to analyze RFI as the primary endpoint, with DR, BCFI, and DFS as secondary endpoints. Because of a nonproportional effect of ELT on DR, time-dependent analyses were performed.
The translational cohort included 2,178 patients (45% BCI (H/I)-High, 55% BCI (H/I)-Low). ELT showed an absolute 10-year RFI benefit of 1.6% (P = 0.10), resulting in an underpowered primary analysis (50% power). ELT benefit and BCI (H/I) did not show a significant interaction for RFI (BCI (H/I)-Low: 10 years absolute benefit 1.1% [HR, 0.70; 95% confidence interval (CI), 0.43–1.12; P = 0.13]; BCI (H/I)-High: 2.4% [HR, 0.83; 95% CI, 0.55–1.26; P = 0.38]; Pinteraction = 0.56). Time-dependent DR analysis showed that after 4 years, BCI (H/I)-High patients had significant ELT benefit (HR = 0.29; 95% CI, 0.12–0.69; P < 0.01), whereas BCI (H/I)-Low patients were less likely to benefit (HR, 0.68; 95% CI, 0.33–1.39; P = 0.29; Pinteraction = 0.14). Prediction of ELT benefit by BCI (H/I) was more apparent in the HER2- subset after 4 years (ELT-by-BCI (H/I) Pinteraction = 0.04).
BCI (H/I)-High versus BCI (H/I)-Low did not show a statistically significant difference in ELT benefit for the primary endpoint (RFI). However, in time-dependent DR analysis, BCI (H/I)-High patients experienced statistically significant benefit from ELT after 4 years, whereas (H/I)-Low patients did not. Because BCI (H/I) has been validated as a predictive marker of EET benefit in other trials, additional follow-up may enable further characterization of BCI's predictive ability.