SAN ANTONIO — Adjuvant paclitaxel and trastuzumab appears to be a reasonable treatment approach for stage I HER-2–positive breast cancer, according to results of a non-randomized, single-arm study presented at the San Antonio Breast Cancer Symposium.
Sara M. Tolaney, MD, MPH, instructor in medicine at Harvard Medical School, and colleagues enrolled 406 patients aged 24 to 85 years with tumors ≤3 cm. Although initial eligibility requirements included node-negative disease, researchers enrolled six patients with one lymph node micrometastasis that had a negative axillary dissection.
Sara M. Tolaney
Fifty percent of the tumors were ≤1 cm, 42% were >1 cm and ≤2 cm, and 9% were >2 cm and ≤3 cm. Fifty-six percent of patients had histologic grade 3 tumors.
“Many, if not the majority of patients with stage I HER-2–positive disease have a sufficiently high enough risk of recurrence to justify the administration of adjuvant therapy, but these patients will derive a smaller absolute benefit from therapy than those who have a higher disease burden,” Tolaney said during a presentation. “In balancing the risks and benefits of treatment, alternative regimens with lower degrees of toxicity are important in this patient population.”
Patients received 80 mg/m2 paclitaxel plus 2 mg/kg trastuzumab (Herceptin, Genentech) for 12 weeks. For 40 weeks thereafter, patients received trastuzumab in 6-mg/kg doses every 3 weeks or 2 mg/kg weekly.
Median follow-up was 3.6 years, or 1,435 patient-years.
Ten DFS events occurred during this time. Four of these events were local or regional recurrences, three were HER-2–negative new contralateral primary breast cancers, two were distant recurrences and one was death from primary ovarian cancer diagnosed during the study.
Researchers calculated a 3-year DFS rate of 98.7% (95% CI, 97.6-99.8).
After stratifying results by tumor size, researchers found that 3-year DFS was 98% (95% CI, 96 to >99.9) for tumors >1 cm and 99.5% (95% CI, 98.4 to >99.9) for tumors ≤1 cm.
The 3-year DFS rate for ER/PR–positive tumors was 98.5% (95% CI, 97 to >99.9%) and 99.2% (95% CI, 97.7 to >99.9) for ER/PR–negative tumors.
The 3-year recurrence-free survival rate was 99.2% (95% CI, 98.3 to >99.9).
The most common adverse events were fatigue (22%), diarrhea (13%) and neuropathy (13%). Fourteen patients experienced grade 3 neuropathy, and no patients experienced grade 4 neuropathy.
Symptomatic congestive heart failure occurred in two patients (0.5%; 95% CI, 0.1-18), although researchers said these patients experienced normalization of left ventricular ejection fraction after treatment a brief interruption in trastuzumab.
Thirteen patients (3.2%; 95% CI, 1.7-5.4) experienced asymptomatic declines in left ventricular ejection fraction, although 11 of these patients resumed treatment after discontinuation.
“We believe paclitaxel and trastuzumab can be considered a reasonable and appealing approach for the majority of patients with stage I HER-2–positive breast cancer,” Tolaney said. “That said, not all patients require adjuvant trastuzumab-based chemotherapy, particularly those patients with T1a tumors.”
For more information:
Tolaney SM. Abstract #S1-04. Presented at: San Antonio Breast Cancer Symposium; Dec. 10-14, 2013; San Antonio.
: The researchers report contract research with and research funding from Genentech and Roche.