Title: An exploratory comparison of MINDACT and TAILORx genomic risk proportions and outcomes in patients with HR+/HER2-, node-negative early-stage breast cancer, stratified by clinical risk

Publication: SABCS 2023, PO1-02-05

Authors

Patrick Neven, Josephine M.N. Lopes Cardozo, Fatima Cardoso, Laura J. van ‘t Veer

Background

Genomic tests provide physicians with critical information to evaluate the risk of distant metastasis and inform treatment plans by identifying those patients who may safely avoid chemotherapy (CT). The 70-gene signature (MammaPrint, MP) through the MINDACT trial and the 21-gene signature (Oncotype DX, ODx) through the TAILORx trial are the only tests validated with level 1A evidence that can be used for CT de-escalation decisions. Differences in trial design have made direct comparison of results difficult. We provide a comparison of MammaPrint and ODx genomic risk distributions and associated survival in patients with HR+/HER2-, node-negative (N0) early-stage breast cancer (EBC), stratified by clinical risk.

Methods

Data from the MINDACT 2021 publication in The Lancet Oncology and landmark TAILORx 2019 publication in The New England Journal of Medicine were reviewed, in addition to publicly available data submitted to the Dutch Health Technology Assessment (HTA) authorities regarding survival data in patients with clinical High Risk in TAILORx. In MINDACT, patients were randomized based on both clinical (as per MINDACT definition) and genomic risk (clinical high/MP low, randomized to treatment according to clinical risk [i.e. CT] vs treatment according to MammaPrint risk [i.e. no CT]), while in TAILORx randomization was based on genomic risk alone. In TAILORx, enrollment for the population in the RS 11–25 group was enriched by 73% to account for the larger than expected non-adherence to randomized treatment plan based on the ODx results, as described in the original publication. This enrichment was only done for the RS 11–25 group. In this analysis, this enrollment enrichment was removed by applying the same proportional 73% corrective factor to the RS 11–25 group. Outcome data are reported for Overall Survival (OS), the only comparable endpoint used in both trials.

Results

This explorative comparison focuses on patients with HR+/HER2- and N0 EBC in MINDACT (n=4225) and TAILORx (n=6686, without population enrichment). Similar proportions of patients identified as candidates for CT de-escalation (MP low risk or ODx RS≤25) were observed in this population of MINDACT (75%) and TAILORx (80%) when removing the RS 11–25 population enrichment in TAILORx (Table). In clinical high risk patients, the proportion with genomic low risk of distant metastasis were also comparable between MINDACT (55%) and TAILORx (63%) (Table). In the original clinical high risk but MammaPrint low risk population treated without CT in MINDACT the reported 8-year OS was 93.9%. In TAILORx, the comparable population of patients (ie. clinical high risk, low genomic risk, not treated with CT) had a 9-year OS of 89.2% in the RS 0–10 group and 91.6% in the RS 11–25 group.

Conclusions

Accounting for differences in trial design and population, comparable proportions of patients with genomic low risk results were observed between MP and ODx, justifying similar rates of CT de-escalation. Patients with clinical high risk tumors who are MammaPrint low risk had an excellent survival at 8 years.