Secondary analyses of the prospective EA1181/CompassHER2 pCR trial identified clinicopathologic and molecular factors associated with pathologic complete response (pCR) after de-escalated neoadjuvant therapy with a taxane plus trastuzumab and pertuzumab (THP) in patients with stage II to IIIA HER2-positive breast cancer. The findings were reported by Tung et al in the Journal of Clinical Oncology.
Study Details
EA1181 is a prospective, single-arm trial evaluating whether patients with stage II to III HER2-positive breast cancer who achieve pCR after neoadjuvant THP can receive less-intensive treatment without compromising outcomes. Eligible patients had operable stage II or IIIA disease; patients with T4 or N3 disease were excluded.
A total of 2,175 patients were enrolled between March 2020 and October 2023, including 781 with HER2-positive/ER-negative disease and 1,394 with HER2-positive/ER-positive disease. Forty-six percent had node-positive disease, and 89% had cT2 or cT3 tumors. Patients received four cycles of trastuzumab and pertuzumab with either weekly paclitaxel for 12 weeks, docetaxel every 3 weeks for four cycles, or, in a small proportion, weekly nab-paclitaxel. pCR was defined as no invasive disease in the breast or axilla (ypT0/Tis, ypN0).
Key Results
Among 2,141 patients who received at least one dose of THP, the overall pCR rate was 43.8% (95% confidence interval [CI] = 41.6%–45.9%). The rate was 63.7% (95% CI = 60.2%–67.1%) in patients with HER2-positive/ER-negative tumors compared with 32.5% (95% CI = 30.0%–35.0%) among those with HER2-positive/ER-positive disease. Within the ER-positive group, pCR rates decreased with increasing ER expression: 62.5% for tumors with 1% to 10% expression, 51.6% for 11% to 70% expression, and 22.5% for expression greater than 70%.
In multivariable analyses, HER2 immunohistochemistry 3+ status was associated with greater odds of pCR in both ER-negative (odds ratio [OR] = 6.31, 95% CI = 3.63–10.94) and ER-positive disease (OR = 6.06, 95% CI = 3.79–9.69). Weekly paclitaxel was associated with greater odds of pCR than docetaxel in ER-negative disease (OR = 1.86, 95% CI = 1.34–2.58).
HER2DX further differentiated response. Among the 569 patients evaluated, pCR rates were 68%, 67%, and 19% in the high-, medium-, and low-score groups, respectively (P < .001). After adjustment for clinicopathologic variables, both high (OR = 2.75, 95% CI = 1.36–5.58) and medium (OR = 4.17, 95% CI = 2.35–7.40) HER2DX scores remained independently associated with greater odds of pCR compared with low scores.
The investigators concluded: “Neoadjuvant THP achieved pCR in nearly two-thirds of patients with [HER2-positive/ER-negative] and one-third with [HER2-positive/ER-positive] breast cancer. Low hormone receptor expression, HER2 [immunohistochemistry] 3+ status, once per week paclitaxel use, and a high HER2DX pCR score were independent predictors of pCR. These findings should help optimize risk stratification and treatment personalization for patients with HER2-positive breast cancer.”
Nadine Tung, MD, of Beth Israel Deaconess Medical Center, Boston, and Harvard Medical School, Boston, is the corresponding author for the Journal of Clinical Oncology article.
DISCLOSURE: The study was supported by the National Cancer Institute. For full disclosures of the study authors, visit ascopubs.org.
