Adam Brufsky, M.D., Ph.D. from the Magee-Womens Cancer Program, part of the UPMC Hillman Cancer Center speaks about the ASCO 2021 Abstract – Utility of the 70-gene MammaPrint assay for prediction of benefit from extended letrozole therapy (ELT) in the NRG Oncology/NSABP B-42 trial.
Link to Abstract:
https://meetinglibrary.asco.org/record/201562/abstract
Description:
The MammaPrint (MP) test, which has 70 genes, predicts the probability of distant recurrence (DR) in hormone-receptor-positive early-stage breast cancer and categorizes it as Low Risk or High Risk. NSABP B-42 looked at ELT in patients (pts) who had been on adjuvant endocrine treatment for at least 5 years (tx). The major goal was to see if MP could be used to identify patients enrolled in NSABP B-42 who would benefit from ELT.
Methodologies:
MP results were provided for a total of 1,866 points from B-42. DR is the primary endpoint. Disease-free survival (DFS) and breast cancer-free interval are secondary goals (BCFI). Pts were categorized as High Risk (MP-H) (MP score 0.000) or Low Risk (MP-L) (MP score > 0.000) for the primary analysis. MP-L subclasses MP Ultralow Risk (MP-UL) (MP score > 0.355) and MP-L but not MP-UL (MP-LNUL) (MP score > 0.000, 0.355) underwent exploratory studies. For treatment by risk group interaction, a likelihood ratio test based on a stratified Cox proportional hazards (PH) model was utilized. The treatment groups were compared using a stratified log-rank test. The stratified Cox PH model was used to calculate hazard ratios and 95 percent confidence intervals.
Outcomes:
706 (38%) of the 1,866 points were MP-H, while 1,160 (62%) were MP-L. 252 MP-ULs (22%) were among the MP-Ls. With the exception of HER2 status, there were no significant changes in the distribution of patient and tumor characteristics between the MP group and the remainder of the B-42 cohort. The ELT impact was stronger in the MP cohort than in the B-42 group as a whole. MP-L (HR = 0.43, 95 percent CI 0.25-0.74, p = 0.002), but not MP-H (HR = 0.65, 0.34-1.24, p = 0.19), had a statistically significant ELT advantage for DR (interaction p = 0.38). In the case of DFS, the ELT advantage was statistically significant in MP-L but not in MP-H (interaction p = 0.015). BCFI also showed similar results (interaction p = 0.006). For all three outcomes, there was a statistically significant ELT advantage in MP-LNUL but not in MP-UL within subcategories of MP-L, although the power in MP-UL was restricted due to the low number of points (Table). 00382070 is the number for the clinical study.
Findings:
MP-L showed a statistically significant ELT advantage, whereas MP-H did not. For DR, the therapy by risk group interaction was not statistically significant, but for DFS and BCFI, it was. In MP-LNUL, the advantage appears to be greater than in MP-UL. 00382070 is the NCT number. Support: Novartis; Agendia; U10CA180868, -180822, U24CA196067.