Title: Utility of the 70-gene MammaPrint assay for prediction of benefit from extended letrozole therapy (ELT) in the NRG Oncology/NSABP B-42 trial

Publication: ASCO 2021, Abstract #502

Authors: Priya Rastogi, Hanna Bandos, Peter C. Lucas, Laura van ‘t Veer, Jia-Perng Jennifer Wei, Charles E. Geyer, Louis Fehrenbacher, Mark Graham, Stephen K. L. Chia, Adam Brufsky, Janice Maria Walshe, Gamini S. Soori, Shaker R. Dakhil, Soonmyung Paik, Sandra M. Swain, Andrea Menicucci, Shiyu Wang, M. William Audeh, Norman Wolmark, and Eleftherios P. Mamounas

Background
The 70-gene MammaPrint (MP) assay predicts risk of distant recurrence (DR) in hormone-receptor positive early-stage breast cancer and classifies cancers as Low Risk or High Risk. NSABP B-42 evaluated ELT in patients (pts) who had completed 5 yrs of adjuvant endocrine therapy (tx). The primary objective was to determine the utility of MP to identify pts enrolled in NSABP B-42 who are likely to benefit from ELT.

Methods
A total of 1,866 pts from B-42 had available MP results. Primary endpoint is DR. Secondary endpoints are disease-free survival (DFS) and breast cancer-free interval (BCFI). For the primary analysis, pts were classified as High Risk (MP-H) (MP score ≤0.000) or Low Risk (MP-L) (MP score > 0.000). Exploratory analyses were performed for MP-L subcategories: MP Ultralow Risk (MP-UL) (MP score > 0.355) and MP-L but not MP-UL (MP-LNUL) (MP score > 0.000, ≤0.355). Likelihood ratio test based on stratified Cox proportional hazards (PH) model was used for treatment by risk group interaction. Stratified log-rank test was used to compare treatment groups. Hazard ratios and 95% CI were computed based on the stratified Cox PH model.

Results

Among 1,866 pts, 706 (38%) were MP-H and 1,160 (62%) were MP-L. Of the MP-L, 252 (22%) were MP-UL. There were no significant differences in the distribution of patient and tumor characteristics between the MP group and the rest of the B-42 cohort, except for HER2 status. ELT effect was more pronounced in the MP cohort than in the overall B-42 population. For DR, there was statistically significant ELT benefit in MP-L (HR = 0.43, 95% CI 0.25-0.74, p = 0.002), but not MP-H (HR = 0.65, 0.34-1.24, p = 0.19) (interaction p = 0.38). For DFS, there was statistically significant ELT benefit in MP-L, but not MP-H (interaction p = 0.015). Similar findings were observed for BCFI (interaction p = 0.006). Within subcategories of MP-L, there was statistically significant ELT benefit in MP-LNUL, but not in MP-UL for all three endpoints, however the power in MP-UL was limited due to low number of pts (Table). Clinical trial information: 00382070.

Conclusion
Statistically significant ELT benefit was observed for MP-L, but not MP-H. The treatment by risk group interaction was not statistically significant for DR, but it was for DFS and BCFI. The benefit appears to be stronger in MP-LNUL than in MP-UL.