SOLD: 9-Week's of Trastuzumab Falls Short in HER2-Positive Breast Cancer

Heikki Joensuu, MD, presenting the results. Photo by © MedMeetingImages/Todd Buchanan 2017

Disease-free survival after 9 weeks of adjuvant trastuzumab and standard chemotherapy was not comparable to disease-free survival after 1 year of adjuvant trastuzumab and standard chemotherapy for women with early-stage HER2-positive breast cancer, according to data from the phase III SOLD trial presented at the 2017 San Antonio Breast Cancer Symposium (SABCS), held December 5–9.

These results support the current practice of extended trastuzumab treatment, according to Heikki Joensuu, MD, PhD, professor in the department of oncology at the Helsinki University Hospital and University of Helsinki in Finland, who presented the results.

According to Joensuu, the 1-year duration of trastuzumab in patients with HER2-positive breast cancer is arbitrary. In four randomized trials that established this standard, trastuzumab was given for 1 year. However, in two other clinical trials with limited statistical power, no difference in disease-free or overall survival was found between patients who received 9 weeks compared with 12 months of trastuzumab.

Therefore, in the SOLD trial, Joensuu and colleagues studies whether 9 weeks of trastuzumab with chemotherapy was noninferior to 1 year of treatment.

The trial included 2,176 patients with early-stage HER2-positive breast cancer and randomly assigned them to 9-weeks trastuzumab or 12-months trastuzumab. Patients received 3 cycles of docetaxel at either 80 mg/m² or 100 mg/m² and trastuzumab three times a week followed by 3 cycles of chemotherapy. Patients in the 9-week arm received no further treatment while those in the 12-month arm received trastuzumab every 3 weeks for 14 cycles.

The median follow-up was 5.2 years. The disease-free survival was 90.5% in the 12-month arm compared with 88% in the 9-week arm (HR, 1.39; 90% CI, 1.12–1.72). However, there was no significant difference in distant disease-free survival (DDFS) or overall survival between the two arms. Five-year DDFS was 93.2% in the 9-week arm and 94.2% in the 12-month arm; five-year overall survival was 94.7% in the 9-week arm and 95.9% in the 12-month arm.

“In all the subgroups we tested the longer arm tended to be better than the shorter one, but we did detect an interaction between docetaxel dose and disease-free survival,” Joensuu said.

Disease-free survival was similar in the 9-week and 12-month arms among those patients who received 100 mg/m² docetaxel. In contrast, among those who received 80 mg/m² docetaxel, 12 months of trastuzumab had superior disease-free survival. According to Joensuu, this suggested that the dose of docetaxel administered with trastuzumab may influence survival outcomes.

Cardiac function was significantly better in the shorter duration arm. Cardiac failure occurred in 3% and 2% of patients in the 12-month and 9-week arms, respectively.

Based on the results of this study, “chemotherapy plus 1 year of anti-HER2 therapy should probably remain the standard treatment,” Joensuu said.