A randomized trial failed to show non-inferiority of 6 months of adjuvant trastuzumab compared with the standard 12 months for HER2-positive breast cancer.
A randomized trial failed to show non-inferiority of 6 months of adjuvant trastuzumab compared with the standard 12 months in women with early-stage HER2-positive breast cancer. The results support the 12-month duration as the continued standard of care.
Though several large trials have shown significant benefit with the anti-HER2 monoclonal antibody trastuzumab along with chemotherapy, “the choice of 12-month treatment duration for trastuzumab was mostly arbitrary, rather than based on pre-existing evidence,” wrote study authors led by Dimitrios Mavroudis, MD, PhD, of the University Hospital of Heraklion in Greece. “A shorter period of trastuzumab treatment would be an attractive option for obvious reasons, like reduced toxicity, convenience to patients, and costs.”
The new trial, conducted by the Hellenic Oncology Research Group, randomized women with axillary node-positive or high-risk node-negative, HER2-positive early breast cancer to either 12 months (241 patients) or 6 months (240 patients) of trastuzumab. All patients also underwent chemotherapy, which was completed in 99% and 98% of patients in each of the two groups. The results were published online ahead of print on May 1 in Annals of Oncology.
After 47 months of follow-up in the 12-month group there were 17 (7.1%) disease relapses; after 51 months of follow-up in the 6-month group, there were 28 (11.7%) relapses (P = .08). Though the difference did not reach significance, the 3-year disease-free survival (DFS) rate was 95.7% in the 12-month patients and 93.3% in the 6-month group, for a hazard ratio of 1.57 (95% CI, 0.86–2.10; P = .137). The median DFS had not yet been reached, and there was also no difference between the groups with regard to overall survival (P = .436).
Toxicity was similar between the groups as well; two patients in the 6-month group stopped trastuzumab due to toxicity (atrial fibrillation and decreased left ventricular ejection fraction [LVEF]); no patients in the 12-month group stopped due to toxicity. There were no toxic deaths in the study.
“Our study failed to demonstrate non-inferiority for the 6-months of adjuvant trastuzumab versus the standard 12-months administration,” the authors wrote. “On the other hand, the 6-months regimen was not proven to be inferior compared to the longer regimen either and therefore the study is inconclusive on the primary endpoint.”
The study did suggest some DFS benefit, however, supporting the current standard of care. This is a similar result to other recent trials on this topic. The authors did note that certain early-stage HER2-positive breast cancers with favorable prognosis may still benefit from the shorter duration of trastuzumab. In other studies, it has appeared that women with small, node-negative tumors may be good candidates for 6-month therapy.