After almost 7 years of follow-up, a large phase II study of patients with small HER2-positive breast cancer found excellent outcomes with the combination of trastuzumab and paclitaxel.
“Retrospective data suggest that patients with small, node-negative HER2-positive tumors have recurrence rates that range from 5% to 30%,” wrote study authors led by Sara M. Tolaney, MD, MPH, of the Dana-Farber Cancer Institute in Boston. “However, randomized trials of adjuvant trastuzumab included a limited number of patients with stage I disease.”
The Adjuvant Paclitaxel and Trastuzumab (APT) trial was the first to specifically address treatment approaches for patients with small, node-negative HER2-positive breast cancer. In its first report in 2015, there was a very high rate of 3-year invasive disease–free survival (98.7%) and low rates of serious adverse events. Most patients in the trial had hormone receptor (HR)-positive, HER2-positive cancer, and these tumors are believed to be associated with later recurrences; to address this issue, the authors now report the 7-year follow-up, published in the Journal of Clinical Oncology.
The study included a total of 410 patients with HER2-positive disease and tumors 3 cm or smaller and negative nodes. It was a single-arm study, since the available retrospective data suggested more than a minimal risk of recurrence; all patients received paclitaxel with trastuzumab for 12 weeks, followed by trastuzumab for a further 9 months.
The median age at enrollment was 55 years, and 67% of the cohort had HR-positive disease. Half the cohort had tumors 1 cm or smaller, and 9% had tumors between 2 and 3 cm in size. The median follow-up period was 6.5 years, covering a total of 2,390 patient-years of follow-up.
There were a total of 23 disease-free survival (DFS) events, including 5 locoregional recurrences (1.2%), 4 distant recurrences (1%), 6 new contralateral breast cancers (1.5%), and 8 deaths without a documented recurrence (2%). The 7-year DFS rate was 93.3% for the full cohort; for just those with HR-positive breast cancer, the 7-year DFS rate was 94.6%, compared with 90.7% in HR-negative patients.
The 7-year recurrence-free interval, which includes distant recurrence, death from breast cancer, and invasive locoregional recurrence, was 97.5%. The 7-year rate of breast cancer–specific survival was 98.6%, and the 7-year overall survival rate was 95.0%.
The new report also included PAM50 gene expression profiling data for 278 patients. Most tumors were classified as HER2 enriched (65.5%); 13.7% were luminal B tumors, 12.6% were luminal A tumors, and 7.9% were basal-like tumors. The authors noted that the low event rate in the trial prevents any meaningful inferences based on molecular subtypes.
Among 230 patients with evaluable genetic data, there were 24 cases (10.4%) of grade 2 or higher paclitaxel-induced peripheral neuropathy, considered among the more burdensome long-term effects of regimens containing paclitaxel. There were no cases of grade 4 neurotoxicity reported. One single-nucleotide polymorphism, rs3012437, was found to be associated with an increased risk of paclitaxel-induced peripheral neuropathy.
“This regimen represents an important step forward in de-escalating therapy to preserve quality of life while achieving excellent outcomes for patients with HER2-positive breast cancer,” the authors concluded.
Mohammad Jahanzeb, MD, of the University of Miami’s Miller School of Medicine, who was not involved in the study, said the researchers “should be congratulated and thanked for this valuable contribution to the body of literature that has resulted in saving thousands of women from overtreatment.” He added that he has treated many patients with the trastuzumab-paclitaxel regimen. “As the efficacy of our treatments improves beyond a certain point, we should not lose sight of the attendant toxicities and find ways to select subgroups where we can de-escalate the treatment in those who will do just as well with less aggressive, better tolerated treatments.”