Adjuvant Paclitaxel/Trastuzumab Tolerable, Benefits Women With Stage I HER2-Positive, Node-Negative Breast Cancer


Key Points

  • Combination trastuzumab and paclitaxel, followed by trastuzumab alone, was well tolerated by women with HER2-positive, node-negative breast cancer < 3 cm.
  • At 3-years follow-up, disease-free survival was 98.7% (P < 0.0001); recurrence or death occurred in 2.5%.
  • This adjuvant regimen should be considered a standard strategy to prevent recurrence in stage I HER2-positive, node-negative breast cancer.

There may be a benefit for treating small HER2-positive tumors and this can be done with little toxicity, according to a multicenter study presented at the 2013 San Antonio Breast Cancer Symposium (Abstract S1-04).

Previous studies of chemotherapy plus anti-HER2 treatment for node-negative patients have included few subjects with tumors < 3 cm and virtually none with tumors ≤ 1 cm, a group for whom treatment has been debated. The findings of the current study offer, for the first time, adjuvant treatment guidelines for recurrence prevention in this group of patients, according to the authors of the study, whose senior author was Eric Winer, MD, Chief of the Division of Women’s Cancers in the Susan F. Smith Center for Women’s Cancers at Dana-Farber Cancer Institute, Boston.

“Smaller, HER2-positive, node-negative breast cancers are thought to have a high enough chance of recurring that many doctors have offered patients a combination of chemotherapy and trastuzumab [Herceptin] to reduce that risk,” Dr. Winer said. “But, as this approach had not been tested in many women with smaller tumors, we have lacked a standard approach to preventing recurrence in this group.”

APT Trial in Women With Small Tumors

The APT study of 406 women with HER2-positive, node-negative tumors < 3 cm was presented in San Antonio by Sara Tolaney, MD, of Dana-Faber, who explained the need to balance risks and benefits in a group of patients who will likely derive a small absolute treatment benefit.

“In balancing the risks and benefits of treatment, the development of regimens with lower degrees of toxicity is particularly important for this patient population,” she said.

The investigators designed a chemotherapy regimen that would be more tolerable than is often given. Patients received paclitaxel 80 mg/m2 plus trastuzumab 2 mg/kg for 12 weeks, followed by 9 months of trastuzumab alone at a dose of 6 mg/kg every 3 weeks. The study was a nonrandomized prospective trial to define the outcomes in a uniformly treated cohort, she said, based on the rationale that “a prospective randomized trial of trastuzumab-based therapy would have been difficult.”

Few Recurrences Observed

After a median follow-up of 3.6 years, 10 of 406 patients experienced a recurrence or death, accounting for 2.5% of the population. There were four recurrences (0.9%), Dr. Tolaney reported.

There were no new contralateral primary breast cancers in the HER2-positive group and three in the HER2-negative group. Distant recurrences were observed in two patients (0.5%). Disease-free survival at 3 years was 98.7% (P < 0.0001); this included 98% of patients with tumors > 1 cm and 99.5% of those with tumors ≤ 1 cm. By hormone receptor status, disease-free survival rates were 98.5% in receptor-positive patients and 99.2% in receptor-negative patients. 

Two patients developed symptomatic congestive heart failure. Few other adverse events were noted.

Dr. Tolaney acknowledged that the study has limitations. It was a single-arm, nonrandomized trial, and about 20% of its patients had T1a tumors that are already associated with a very favorable prognosis. Also, two-thirds had hormone receptor–positive tumors, and recurrences with these tumors may be delayed beyond the time from of this study. Nevertheless, she suggested that paclitaxel plus trastuzumab can be considered “a reasonable and appealing approach for the majority of patients with stage I HER2-positive breast cancer.”

Dr. Winer added that for this population, the paclitaxel/trastuzumab doublet “should be considered one of the standard strategies for recurrence prevention.”

The study was funded by Genentech.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.