A subgroup analysis of Short-HER looked at the differences in 5-year DFS rates for 9 weeks vs 1 year of trastuzumab for HER2+ breast cancer patients.
A subgroup analysis of the Short-HER study showed no differences in 5-year disease-free survival (DFS) rates between 9 weeks and 1 year of trastuzumab treatment for certain low-risk patients with HER2-positive breast cancer, while high-risk patients do derive substantial benefit from the longer duration. The substantially reduced cardiotoxicity with the shorter duration of therapy suggests this could be an important option for some patients.
The full results of the Short-HER study were recently reported; the trial failed to show noninferiority of 9 weeks of trastuzumab in a full cohort of 1,254 patients, though an analysis suggested an 80% probability that the short duration of therapy would be noninferior to the full year. The new subgroup analysis was presented by Pierfranco Conte, MD, of the University of Padua in Italy, at the European Society for Medical Oncology (ESMO) 2018 Congress, held in Munich.
The researchers broke the full cohort down into three risk groups based on pathologic tumor size and nodal status. The low-risk group included pT of 2 cm or less and N0 nodal status; intermediate-risk patients had pT of 2 cm or less and any N category or a tumor larger than 2 cm and N 0–3; high-risk patients had tumors larger than 2 cm and N 4+. These three groups represented 37.5%, 51.9%, and 10.5% of the cohort, respectively.
In the low-risk patients, the 5-year DFS rate was 91% with 1 year of trastuzumab treatment, compared with 92% with 9 weeks of therapy, for a hazard ratio (HR) of 0.96 (95% CI, 0.56–1.66). In intermediate-risk patients, the results were again similar, at 87% and 86%, respectively, for an HR of 1.05 (95% CI, 0.71–1.54). The longer duration of therapy was still clearly beneficial in the high-risk patients, with a 5-year DFS rate of 80% compared with 60% with 9 weeks of therapy, for an HR of 1.94 (95% CI, 1.07–3.53).
Conte stressed that the study was not powered to firmly conclude that the shorter duration of therapy is noninferior to the longer duration.
There were clear differences, however, with regard to cardiac toxicity. In the 1-year trastuzumab patients, 14.6% of low-risk patients had a grade 2 or higher cardiac event, compared with 5.1% with 9 weeks of treatment, for a relative risk (RR) of 2.85 (95% CI, 1.51–5.36). In intermediate-risk patients, these rates were 11.6% and 3.9%, for an RR of 2.9 (95% CI, 1.57–5.35), and in the high-risk group they were 14.1% and 3.3%, for an RR of 4.22 (95% CI, 0.96–18.5).
“Physicians can stop trastuzumab before 1 year in patients who develop a cardiac event during treatment without compromising efficacy and can consider shorter-duration trastuzumab treatment in patients at risk of cardiac toxicity and a low or intermediate risk of breast cancer relapse,” Conte said, according to a press release.
Nadia Harbeck, MD, of the University of Munich, commented on the study for ESMO, and stressed the clear benefit with longer-duration trastuzumab in the high-risk group. “The results may impact on clinical decision making, although it is an exploratory analysis of a negative trial so does not meet the criteria to be practice changing,” she said. “I think it will influence clinicians and patients in that if patients cannot complete 1 year of trastuzumab, those patients with low tumor burden can feel reassured that they have not lost out on efficacy.”