ADAPT HER2+/HR- Shows ‘Excellent’ Outcomes With De-Escalated Neoadjuvant Approach

Author: By Lynda Williams, Senior medwireNews Reporter 

medwireNews: Phase II trial survival results reported at the 2021 ASCO Annual Meeting add support for the use of a 12-week de-escalated neoadjuvant regimen of trastuzumab plus pertuzumab and paclitaxel for women with HER2-positive, hormone receptor (HR)-negative early breast cancer. 

Previously, the ADAPT HER2+/HR- investigators reported pathological complete response (pCR) rates of 90% for the 42 patients randomly assigned to receive dual HER2-targeted therapy with paclitaxel and 34% for the 92 patients given only the dual HER2-targeted therapy. 

For patients with a pCR at time of surgery, adjuvant therapy could be omitted, as occurring in 79.0% of patients given dual HER2-targeted therapy plus paclitaxel and 29.0% of patients given only trastuzumab plus pertuzumab, explained Nadia Harbeck, from the University of Munich in Germany. 

After a median follow-up of 59.9 months, the 5-year invasive disease-free survival (DFS) rates were a statistically comparable 98% after neoadjuvant dual HER2-targeted therapy plus paclitaxel and 87% after neoadjuvant dual HER2-targeted therapy alone. 

The corresponding 5-year rates of distant DFS (98 vs 92%) and overall survival (98 vs 94%) were also statistically comparable, the presenter said. 

But among the patients given dual HER2-targeted therapy alone, the 5-year rate of invasive DFS numerically differed between the patients with and without a pCR, at 98% versus 83%, although this did not reach statistical significance, perhaps because of the small group numbers. 

Further analysis based on the presence of an early response at the 3-week biopsy – defined as a 30% or greater decrease in Ki-67 or fewer than 500 invasive tumour cells – identified a non-sensitive population with basal disease and low HER2 expression, which comprised 33.7% of patients. 

These patients with non-sensitive tumours were significantly more likely to experience distant disease than other participants regardless of whether they received paclitaxel. And among patients who received only dual HER2-targeted therapy, the 5-year invasive DFS rate was 79% for non-sensitive patients versus 93% of other patients. 

“In [ADAPT HER2+/HR-] early pCR after only 12 weeks of neoadjuvant paclitaxel plus pertuzumab plus trastuzumab was strongly associated with improved outcome and may thus serve as a predictive clinical marker for further treatment de-escalation”, Nadia Harbeck summarised. 

Describing the pCR and survival results in the study as “excellent” regardless of adjuvant chemotherapy use, the presenter suggested that chemotherapy-free regimens are “promising in highly sensitive tumours with early response.” 

Acknowledging that other de-escalation trials, such as COMPASS and DECRESCENDO are ongoing, Nadia Harbeck concluded that “future investigation of chemotherapy-free regimens needs to be focused on selected patients”, such as those with early responses to neoadjuvant treatment, strong HER2 expression, non-basal-like disease and RNA signatures predictive of a good response. 

Reference  

Harbeck N, Gluz O, Christgen M, et al. De-escalated neoadjuvant pertuzumab+trastuzumab with or without paclitaxel weekly in HR-/HER2+ early breast cancer: ADAPT-HR-/HER2+ biomarker and survival results. J Clin Oncol;39(suppl 15; abstr 503). DOI:10.1200/JCO.2021.39.15_suppl.503