Pathological complete response (pCR) is a surrogate biomarker of survival in Human Epidermal Growth Factor Receptor 2-positive (HER2+) breast cancer (BC) and more likely to occur in hormonal receptor (HR) negative (-). In the early efficacy and safety analysis of the ZoNAnTax trial, 4 cycles of doxorubicin/cyclophosphamide with ZOL, followed by 4 cycles of docetaxel with trastuzumab and ZOL prior to surgery induced similar pCR rates in HR positive (+) 40% and HR- 44%, and were well tolerated. The translational analysis demonstrated the mechanistic behind the clinical results, including the crosstalk between the WNT, HER2 and estrogen pathways with the mevalonate pathway and the modulation by ZOL being relevant to the treatment response in HR+/HER2+BC. Here we present the 5-years (5y) disease-free survival (DFS) and overall survival (OS) for the entire study sample according to pCR status and stratified by HR.
Kaplan-Meier Survival curves were estimated, and the Log-rank statistical test was performed to evaluate the hypothesis of survival differences between groups according to pCR status at 5% level of significance.
From 71 HER2+ BC patients with stage IIA-IIIB, 58 were eligible for efficacy analysis. Overall DFS rate was 79.3%, for patients achieving pCR was 83.3% versus (vs) non-pCR 76.5% (p=0.57), and for HR+ was 81% vs HR- 75% (p=0.58). DFS according to pCR status stratified by HR for HR- achieving pCR was 71.4% vs non-pCR 71.8% (p=0.72) and for HR+ achieving pCR was 88.2% vs non-pCR 76% (p=0.32). Overall OS rate was 86.2%, for patients achieving pCR was 95.8% vs non-pCR 79.4% (p=0.08), and for HR+ was 85.7% vs HR- 87.5% (p=0.91). OS according to pCR status stratified by HR for HR- achieving pCR was 100% vs non-pCR 77.8% (p=0.23) and for HR+ achieving pCR was 94.1% vs non-pCR 80% (p=0.20).
Taken together with the safety and early efficacy, the long-term benefit of the ZoNAnTax regimen demonstrating DFS and OS rates as high as reported by pivotal studies that contained Pertuzumab in the same setting, suggests that adding ZOL as a repositioning drug to the NT of HER2+ BC should be considered.
NCT01472146.
Instituto Nacional de Cancer Hospital do Cancer III - INCA Rio de Janeiro, Brazil, 20560-120.
Has not received any funding.
All authors have declared no conflicts of interest.