Adding a second HER2-targeted agent, pertuzumab, to adjuvant trastuzumab plus chemotherapy had a modestly favorable effect on outcomes in women with early-stage, HER2-positive breast cancer. The phase 3 APHINITY trial of more than 4800 women showed that dual HER2-targeted therapy reduced the risk for invasive breast cancer by 19% compared with single-agent HER2-targeted therapy in this setting,1 said lead investigator Gunter von Minckwitz, MD, PhD, President of the German Breast Group in Neu-Isenburg, Germany, at the 2017 meeting of the American Society of Clinical Oncology (ASCO).
In APHINITY, at an early follow-up of 3 years, the rates of invasive disease-free survival (IDFS) were 93.2% in the trastuzumab alone arm compared with 94.1% in the pertuzumab plus trastuzumab arm, an absolute difference of approximately 1% (hazard ratio, 0.81; P = .045).
Although the results proved favorable, additional HER2-directed therapy comes at additional cost and, therefore, may not be appropriate for women at low risk for recurrence, experts suggest. In the overall APHINITY population, the number needed to treat to prevent 1 invasive disease relapse was 112.
APHINITY included 4805 women with adequately excised HER2-positive, pT1-3 early-stage breast cancer who were randomized to standard adjuvant therapy (1 year of trastuzumab plus chemotherapy) plus placebo or 1 year of standard adjuvant therapy plus pertuzumab. Eligible patients had either node-positive disease or node-negative disease (pN0) and a tumor size >1.0 cm. Patients with pN0, T1b tumors with high-risk features were initially eligible.
Overall, 63% of patients had node-positive disease and 36% had hormone receptor–positive disease, with a similar proportion of patients with either disease characteristic in the 2 treatment groups.
At a median follow-up of 45.4 months, 171 (7.1%) patients in the pertuzumab plus trastuzumab arm had developed invasive breast cancer, compared with 210 (8.7%) patients in the trastuzumab plus placebo arm.
The benefit from pertuzumab was slightly greater among patients with node-positive disease; in this group, the 3-year IDFS rate was 92% with pertuzumab plus trastuzumab versus 90.2% with trastuzumab plus placebo (P = .019). In patients with node-negative cancer, IDFS was not influenced by pertuzumab at the early analysis.
“These are very early results, but given that the absolute benefit from adding pertuzumab was modest, we should consider using it primarily in women with the highest risk—those with node-positive and hormone receptor–negative breast cancer,” said Dr von Minckwitz.
Development of heart failure plus a decline in left ventricular ejection fraction (LVEF) or heart-related death occurred in 0.7% of patients in the pertuzumab/trastuzumab group and in 0.3% of patients in the trastuzumab/placebo group. Three additional patients in the pertuzumab/trastuzumab group had an asymptomatic decline in LVEF compared with placebo (7 vs 4, respectively). Grade 3 diarrhea was more common with pertuzumab use, occurring in 9.8% of patients, compared with 3.7% of those who received placebo.
The optimal duration of adjuvant therapy is 1 question that remains after APHINITY, noted Dr von Minckwitz. “It is possible that patients may not need a full year of treatment after surgery; 6 months may be enough,” he said.
“It’s promising that some women in this study benefited more from treatment with two HER2-targeted therapies rather than one, but it’s clear this approach may not be advantageous for women with a low risk of recurrence,” said ASCO expert Harold J. Burstein, MD, PhD, Associate Professor of Medicine, Harvard Medical School, Boston, Massachusetts.
One year of adjuvant pertuzumab would increase the cost of standard trastuzumab plus chemotherapy from approximately $56,000 to $150,500, noted Carey K. Anders, MD, Associate Professor, Department of Medicine, University of North Carolina, Chapel Hill, an invited discussant at ASCO 2017. “The cost implications are quite substantial,” she said.
1. Von Minckwitz G, Procter MJ, De Azambuja E, et al. APHINITY trial (BIG 4-11): a randomized comparison of chemotherapy (C) plus trastuzumab (T) plus placebo (Pla) versus chemotherapy plus trastuzumab (T) plus pertuzumab (P) as adjuvant therapy in patients (pts) with HER2-positive early breast cancer (EBC). J Clin Oncol. 2017;35 (suppl):Abstract LBA500.