SABCS 2017: SOLD Trial Data Support Current Standard 12-Month Adjuvant Trastuzumab for HER2-Positive Breast Cancer
Disease-free survival after 9 weeks of adjuvant trastuzumab (Herceptin) and standard chemotherapy was not comparable to disease-free survival after 12 months of adjuvant trastuzumab and standard chemotherapy for women with early-stage HER2-positive breast cancer, supporting the current practice of extended trastuzumab treatment, according to data from the phase III Synergism or Long Duration (SOLD) clinical trial, presented by Joensuu et al at the 2017 San Antonio Breast Cancer Symposium (Abstract GS3-04).
The study, however, found no substantial difference in the secondary endpoints of distant disease–free survival and overall survival between the 12-month trastuzumab arm and the 9-week trastuzumab arm.
“The choice for 1-year duration of trastuzumab administration in patients with HER2-positive breast cancer was arbitrary and not based on research data,” said Heikki Joensuu, MD, Professor in the Department of Oncology at the Helsinki University Hospital and University of Helsinki in Finland.
Current Standard of Care
In all four large randomized trials that established the current standard treatment (chemotherapy plus trastuzumab), trastuzumab was given for 1 year and, therefore, the 1-year duration became the standard, Dr. Joensuu explained. In two randomized trials with relatively limited statistical power, there was no statistical difference in disease-free or overall survival between those who received 9 weeks vs 12 months of trastuzumab.
“The current standard treatment is lengthy, costly, and occasionally associated with cardiac adverse events,” Dr. Joensuu said. Although trastuzumab is well tolerated in general, the most important adverse effect is congestive heart failure, which occurred in less than 3% of patients treated in the pivotal clinical trials. However, the risk for trastuzumab-related congestive heart failure is likely higher in elderly patients who have a preexisting risk for [the condition], he added.
SOLD Trial
Dr. Joensuu and colleagues studied whether it is sufficient to administer trastuzumab with chemotherapy only for a brief period of time (9 weeks) instead of the standard practice of administering trastuzumab both during chemotherapy (for 9 weeks) and then as a single agent after stopping chemotherapy (for 12 months).
“We could not demonstrate that the experimental treatment [9 weeks of trastuzumab] is similar in efficacy to the standard treatment [12 months of trastuzumab] in terms of disease-free survival,” said Dr. Joensuu. “There was, however, not much difference between the groups in two other important clinical endpoints, distant disease–free survival and overall survival, which were secondary [endpoints] of the study.”
In SOLD, the investigators randomly assigned (1:1) 2,176 patients with early-stage HER2-positive breast cancer to the 9-week trastuzumab arm or the 12-month trastuzumab arm.
Patients in both arms received three cycles of docetaxel (80 mg/m2 or 100 mg/m2) and trastuzumab three times a week, followed by three cycles of chemotherapy. Patients in the 9-week arm received no further treatment, whereas those in the 12-month arm received trastuzumab every 3 weeks for 14 cycles. Patients with estrogen receptor–positive cancer received appropriate endocrine treatment and radiation therapy per guidelines.
Major Findings
In the 12-month arm, the disease-free survival rate was 90.5%, compared with 88% in the 9-week arm. There was no substantial difference in distant disease–free survival and overall survival between the two arms: 5-year distant disease–free survival was 93.2% in the 9-week arm and 94.2% in the 12-month arm; 5-year overal survival was 94.7% in the 9-week arm and 95.9% in the 12-month arm.
“Interestingly, we detected a significant interaction between the dose of docetaxel given concomitantly with trastuzumab in preplanned subgroup analyses,” noted Dr. Joensuu.
Among patients who received docetaxel at 100 mg/m2, disease-free survival was similar in the 9-week and 12-month arms, but among those who received docetaxel at 80 mg/m2, 12 months of trastuzumab yielded disease-free survival that was superior to that seen with 9 weeks, suggesting that the dose of docetaxel administered with trastuzumab may influence survival outcomes. “This, and brief dual inhibition of HER2 with trastuzumab and pertuzumab (Perjeta), each given with an adequate dose of a taxane, warrant further studies,” he said.
“The shorter trastuzumab treatment was safer to the heart than the longer treatment,” added Dr. Joensuu. Cardiac failure occurred in 3% and 2% of patients in the 12-month and 9-week arms, respectively. Patients in the 9-week arm had significantly higher cardiac left-ventricular ejection fractions than patients in the 12-month arm, but the absolute differences were small, and the ejection fractions mostly returned to the baseline level within 3 years after the date of randomization, Dr. Joensuu said.
A limitation of the study is that because of cancer characteristics and some logistical issues, including not being able to reach the planned number of disease-free survival events within a reasonable time frame, the study had lower statistical power than planned.
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