The addition of a second HER2-targeting treatment, pertuzumab, to trastuzumab and chemotherapy improved invasive disease–free survival compared with placebo in patients with HER2-positive early breast cancer who have undergone surgery, according to the results of the APHINITY trial (abstract LBA500) presented at the 2017 American Society of Clinical Oncology (ASCO) Annual Meeting, held June 2–6.
“The treatment effect was homogeneous throughout all subgroups; however, the node-positive and hormone receptor–negative cohorts appeared to derive the most benefit at the current point of time, but, of course, this might change with longer follow-up,” said researcher Gunter von Minckwitz, MD, PhD, president of the German Breast Group in Neu-Isenburg, Germany.
The trial included 4,805 patients who had undergone lumpectomy and randomly assigned them to standard adjuvant chemotherapy plus 1 year of either trastuzumab plus pertuzumab or trastuzumab plus placebo.
The addition of pertuzumab to chemotherapy and trastuzumab resulted in a 19% reduction in risk for invasive progression (hazard ratio [HR], 0.81; 95% CI, 0.68–1.00; P = .045) compared with trastuzumab alone. The estimated invasive disease–free survival at 3 years was 94.1% for pertuzumab compared with 93.2% for the control arm.
According to von Minckwitz, the benefit of adding pertuzumab was slightly greater in patients with node-positive disease, which was about two-thirds of patients enrolled. In this group, there was a relative risk reduction of invasive progression of 23% (HR, 0.77; 95% CI, 0.62–0.96; P = .019). The 3-year invasive disease–free survival rate was 92.0% for patients assigned pertuzumab compared with 90.2% for trastuzumab alone. The addition of pertuzumab had no influence on disease-free survival in patients with node-negative disease.
In women with hormone receptor–negative disease, there was a risk reduction of 24% (HR, 0.76; 95% CI, 0.56–1.04). At 2 years, the rate of invasive disease–free survival was 91.0% for pertuzumab compared with 88.7% for trastuzumab/placebo.
The researchers established a combined primary cardiac endpoint of severe heart failure and cardiac death; 17 patients assigned pertuzumab experienced this endpoint compared with 8 patients in the placebo group. Most of the grade 3 or higher adverse events were hematologic, including neutropenia, febrile neutropenia, and anemia. More patients assigned pertuzumab experienced grade 3 or worse diarrhea (9.8%) compared with patients assigned placebo (3.7%).
“Continued follow-up is planned for up to 10 years and is important for overall survival, longer-term invasive disease–free survival, and safety analyses,” von Minckwitz noted.
Commenting on the study, ASCO Expert Harold J. Burstein, MD, PhD, FASCO, said that these results are clinically meaningful for patients with HER2-positive breast cancer. “APHINITY is a step forward in the treatment of HER2-positive breast cancer and the relatively narrow benefit seen in numerical terms reflects the overall good prognosis of these patients,” he said.