Trastuzumab for 9 Weeks Fails to Show Noninferiority in HER2-Positive Breast Cancer

Get Permission

ANOTHER TRIAL has validated that 1 year of adjuvant trastuzumab (Herceptin) remains the standard in HER2-positive breast cancer, but the margin of difference, compared with just 9 weeks of the drug, was slim, based on the findings of the phase III SOLD trial reported at the 2017 San Antonio Breast Cancer Symposium.

Although the outcomes favored 1 year of adjuvant trastuzumab, the differences were in the range of 1% to 2%, and the longer duration was associated with significantly more cardiac toxicity, the study’s lead investigator Heikki Joensuu, MD, Professor of Oncology at the University of Helsinki and Research Director at the Comprehensive Cancer Center, Helsinki University Hospital in Finland, acknowledged. 

Heikki Joensuu, MD

Heikki Joensuu, MD

“The difference in 5-year distant disease–free survival is just one percentage point—so a shorter treatment may be an option for some patients. But we could not show that 9 weeks of trastuzumab plus docetaxel was noninferior to the standard treatment in terms of disease-free survival [the primary endpoint],” Dr. Joensuu said. “Overall, the results speak in favor of longer treatment. Chemotherapy plus 1 year of anti-HER2 therapy should remain the standard.” 

SOLD Trial Details 

THE PREVIOUS FinHer study, reported in 2006 and also led by Dr. Joensuu, evaluated 9 weeks of adjuvant trastuzumab (vs observation) in 232 women and found this short duration of anti-HER2 therapy reduced the risk of recurrence or death by 58% (P = .01).2 “It showed a benefit, but the size was small, and the docetaxel dose was 100 mg/m2 in about a half. Many patients now get a smaller dose. FinHer was a starting point, but we needed a much larger study of 9 weeks of trastuzumab,” he said at a press briefing.

The phase III SOLD trial enrolled 2,176 patients with early-stage HER2-positive breast cancer treated at 65 centers in Finland, Sweden, the United Kingdom, Belgium, New Zealand, Iceland, and Serbia. Patients had node-negative (60%) or node-positive (40%) disease; patients with node-negative disease were required to have a primary tumor > 5 mm. 

The study compared the outcomes for 9 weeks of trastuzumab given as part of adjuvant chemotherapy (three cycles of docetaxel [80 or 100 mg/m2] plus trastuzumab followed by fluorouracil, epirubicin, cyclophosphamide [FEC]), vs the same regimen with trastuzumab continued for a total of 1 year. Patients in the 9-week arm received no further trastuzumab after stopping chemotherapy. In both groups, locoregional radiotherapy was given according to institutional practice, and women with hormone receptor–positive disease received at least 5 years of endocrine therapy. 


  • In the phase III SOLD trial, investigators compared outcomes for 9 weeks vs 1 year of adjuvant trastuzumab in 2,176 patients with early HER2-positive breast cancer in 7 countries.
  • The noninferiority trial did not show 9 weeks of the drug was as good as 1 year of trastuzumab, although the differences in benefit were small.
  • The primary outcome, disease-free survival at 5 years, was 90.5% for the 1-year arm vs 88.0% for the 9-week arm. Overall survival was 95.9% and 94.7%, respectively, and distant disease–free survival was 94.2% and 93.2%, respectively.
  • The longer treatment duration resulted in greater cardiac toxicity.

The study was revised to have a noninferiority design, based on the belief that initial assumptions for disease-free survival were too low. The final assumption was that 5-year disease-free survival would be 85%; the noninferiority margin was 1.3. 

Noninferiority Not Shown 

AFTER A MEDIAN follow-up of 5.2 years, the primary endpoint, disease-free survival, was 90.5% for the 1-year arm vs 88.0% for the 9-week arm (hazard ratio [HR] = 1.39). Overall survival was high in both arms: 95.9% for the 1-year arm and 94.7% for the 9-week arm (HR = 1.36), also favoring the longer treatment. Distant disease–free survival at 5 years was 94.2% and 93.2%, respectively (HR = 1.24). 

“There was not much difference between the groups in two other important clinical endpoints, distant disease–free survival and overall survival,” Dr. Joensuu commented. 

The docetaxel dose was either 80 or 100 mg/m2, by physician’s choice, which may have influenced the outcome, he suggested. Among patients receiving the lower dose, 1 year of trastuzumab yielded better disease-free survival than 9 weeks of the drug, but this was not seen in patients receiving 100 mg/m2 of docetaxel. 

For patients receiving docetaxel at 80 mg/m2, the disease-free survival was 91.3% with 1 year and 86.8% with 9 weeks (HR = 1.66). For patients receiving 100 mg/m2, the disease-free survival was 87.8% with 1 year vs 92.2% with 9 weeks (HR = 0.71). The P value for interaction between docetaxel dose and disease-free survival was statistically significant (P = .007). 

Cardiac Safety 

A CLEAR ADVANTAGE was seen for the shorter duration in terms of cardiac safety. Patients treated with 9 weeks of trastuzumab had better maintenance of left-ventricular ejection fraction (P < .001) and fewer cardiac events. In the 9-week arm, there were 22 (2.0%) protocol-defined cardiac adverse events compared with 42 (3.9%) in the 1-year arm (P = .012), and congestive heart failure was observed in 21 (1.9%) and 36 (3.3%) patients, respectively (P = .046), he reported. 

For women with heart disease, and when the cost of the drug is a limiting factor, “9 weeks of trastuzumab is better than nothing,” shared Dr. Joensuu, but other patients should be afforded 1 year of treatment when possible. ■

DISCLOSURE: Dr. Joensuu is an advisor for Neutron Therapeutics; has received consultation fees from Orion Pharma; has Orion Pharma, Faron Pharmaceuticals, and Sartar Therapeutics stock ownership interest; and has a coappointment with Orion Pharma. 


1. Joensuu H, et al: 2017 San Antonio Breast Cancer Symposium. Abstract GS3- 04. Presented December 7, 2017. 

2. Joensuu H, et al: N Engl J Med 354:809-820, 2006.