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NeoALTTO: pCR associated with EFS in HER-2–positive breast cancer
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Pathologic complete response strongly correlated with EFS in a large cohort of patients who underwent neoadjuvant treatment for HER-2–positive breast cancer, according to study results.
“The results … do not suggest that we should change the standard of care as yet,” Martine Piccart-Gebhart, MD, PhD, chair of the Breast International Group in Brussels, said during a press conference. “What this trial indicates is that it is possible that, for the particular subgroup of HER-2–positive, hormone receptor-negative patients, we could potentially use the neoadjuvant model to speed up the approval of new anti-HER–2 agents. That is encouraging because adjuvant trials in breast cancer require many years of follow-up, are very time-consuming and expensive, and require thousands of patients.”
Martine Piccart-Gebhart
The NeoALTTO trial included 455 patients with HER-2–positive primary breast cancer with tumors larger than 2 cm in diameter.
Researchers randomly assigned patients to one of three neoadjuvant treatment regimens: lapatinib (Tykerb/Tyverb, GlaxoSmithKline) 1,500 mg/daily (n=154); trastuzumab (Herceptin, Genentech) 4 mg/kg IV loading dose followed by 2 mg/kg IV weekly (n=149); or lapatinib 1,000 mg/daily with trastuzumab (n=152) for 6 weeks, followed by continuation of the anti-HER–2 targeted treatment in combination with paclitaxel for 12 weeks. After the completion of all neoadjuvant therapy, patients underwent surgery. After surgery, patients underwent adjuvant chemotherapy and then received 34 weeks of the same HER-2–targeted therapy administered in the neoadjuvant phase, radiotherapy and adjuvant endocrine therapy, if indicated.
The total treatment course was 52 weeks. A 10-year follow-up is planned.
The researchers previously reported that the neoadjuvant combination therapy was associated with a higher rate of pathologic complete response (pCR) — defined as no invasive disease in the breast — than either single-agent arm (51.3% for lapatinib plus trastuzumab vs. 29.5% for trastuzumab alone and 24.7% for lapatinib alone).
In a landmark analysis, Piccart-Gebhart and colleagues evaluated the association between EFS and pCR, independent of treatment arm. In this analysis, pCR was defined as no invasive disease in the breast and axilla.
Overall, the rate of 3-year EFS was 86% among patients who achieved pCR compared with 72% among patients who did not achieve pCR (HR=0.38; P=.003).
Among patients with hormone receptor-negative tumors, the rate of 3-year EFS was 85% among those who achieved pCR vs. 65% among those who did not achieve pCR (HR=0.34; P=.001).
Three-year OS was 94% among patients who achieved pCR vs. 87% among those who did not (HR=0.35; P=.005). Among patient with hormone receptor-negative disease, OS was 94% among those who achieved pCR vs. 80% for those who did not (HR=0.29; P=.003).
“It is possible with longer follow-up that we will also see a bigger treatment effect in the hormone receptor-positive subgroup, but clearly this trial provides further evidence that HER-2–positive, hormone receptor-negative and HER-2–positive, hormone receptor-positive subgroups are two different diseases.”
For more information:
Piccart-Gebhart M. Abstract #S1-01. Presented at: San Antonio Breast Cancer Symposium; Dec. 10-14, 2013; San Antonio.
Disclosure: The study was supported by GlaxoSmithKline. Piccart-Gebhart reports consultant fees from Roche. Her institution received research funding from GlaxoSmithKline.
Perspective
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Clifford A Hudis, MD
In this study, we see two things that are important.
First, the combination of lapatinib and trastuzumab increased the in-breast response rate, and that echoes what has been seen in some prior reports — for example, the CALGB 40601 trial.
In addition, we see a strengthening of the association between obtaining a pathologic complete response (pCR) and long-term EFS or OS. The big issue that faces us still is the demonstration of a threshold effect, or a delta. That is, how much of an improvement in pCR predicts a measurable improvement in DFS or OS?
That really speaks to the role of pCR as a surrogate — a key issue, as we are developing so many drugs in this setting.
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