Can Trastuzumab Duration Be Shortened in HER2-Positive Breast Cancer?

October 1, 2018

The Short-HER study was unable to show noninferiority of 9 weeks of trastuzumab compared with the standard 1 year in women with HER2-positive breast cancer.

Adding to a growing list of similar results, the Short-HER study was unable to show noninferiority of 9 weeks of trastuzumab compared with the standard 1 year when given along with chemotherapy in women with HER2-positive breast cancer. Shorter administration does, however, reduce the risk of cardiotoxicity.

“Adjuvant pivotal trials with 1-year trastuzumab have significantly improved the prognosis of HER2-positive early breast cancer,” wrote study authors led by Pierfranco Conte, MD, of the Istituto Oncologico Veneto in Italy. Several studies have attempted to reduce the duration of trastuzumab, though most have failed to show noninferiority.

The Short-HER study included a total of 1,254 patients (one was excluded after randomization) from 82 centers with HER2-positive breast cancer; they were randomized to receive either chemotherapy plus 1 year of trastuzumab (Arm A, 627 patients) or 9 weeks of trastuzumab (Arm B, 627 patients). Patients were a mean age of 55 years, 54% had node-negative disease, and 68% had hormone receptor–positive tumors; they were followed for a median of 6 years, and the results were published in Annals of Oncology.

The 5-year disease-free survival rate was 88% with the longer administration and 85% with the shorter administration, for a hazard ratio (HR) of 1.13 (95% CI, 0.89–1.42); this crossed the noninferiority margin set at 1.29. The 5-year overall survival rate was 95.2% in Arm A and 95.0% in Arm B, for an HR of 1.07 (95% CI, 0.74–1.56).

A total of 27 patients in the short administration group (4.3%) experienced a grade 2 or worse cardiac adverse event, compared with 82 patients (13.1%) in the long administration arm, for a risk ratio of 0.33 (95% CI, 0.22–0.50; P < .001). Permanent discontinuation of trastuzumab was required in 8.5% of patients in the long administration group and in 3.4% of those in the short administration group.

“The noninferiority of 9 weeks trastuzumab cannot be claimed,” the authors concluded. “However, a shorter trastuzumab administration could be an option for those patients who experience cardiac events and for those with a low risk of relapse.”

Sara A. Hurvitz, MD, of the UCLA Medical Center, who was not involved with the study, noted that four of five studies have now failed to show the noninferiority of a shorter trastuzumab regimen. “There are patients who probably don’t require a full year of trastuzumab,” she said, “but none of these studies have been very good at defining who those patients are.” The studies have included mixed populations of patients, and most have been using anthracycline-based chemotherapy, which can make the toxicity profile appear worse.

Hurvitz said that the patients she would feel most comfortable reducing trastuzumab duration in are those who are low-risk-lymph node–negative, estrogen receptor–positive, without high-grade tumors. Physicians might also be more willing to use a non–anthracycline-based chemotherapy regimen in these patients.

“If I was going to be de-escalating therapy, I’d probably use that type of regimen, rather than reducing the amount of the very important HER2-targeted therapy that is really not associated with much toxicity, if you’re avoiding an anthracycline,” she said in an interview. She noted, though, that the idea of using a reduced course of trastuzumab may be most relevant in parts of the world where the agent is difficult to find or afford.