APHINITY trial hints at modest benefit of adding pertuzumab to standard-of-care for HER2-positive breast cancer
The addition of pertuzumab to standard-of-care therapy may convey a positive, albeit modest, effect for women with HER2-positive breast cancer, according to findings from the APHINITY* trial presented at the annual meeting of the American Society of Clinical Oncology (ASCO 2017) held in Chicago, Illinois, US.
“[The] advent of HER2-targeted therapy changed the outlook for [women with HER2-positive breast cancer],” said lead author Dr Gunter von Minckwitz, president of the German Breast Group, Neu-Isenburg, Germany. “Our early findings suggest that we may be able to further improve outcomes for some women by adding a second HER2-targeted treatment, without increasing risk for serious side effects.”
Within 8 weeks of undergoing surgery, 4,805 women with HER2-positive primary breast cancer were randomized to undergo chemotherapy (both anthracycline and non-anthracycline regimens were allowed) for 18 weeks plus trastuzumab in addition to either pertuzumab (n=2,400) or placebo (n=2,405) for 52 weeks.
The incidence of invasive breast cancer was lower among patients on pertuzumab plus trastuzumab vs trastuzumab only (7.1 percent vs 8.7 percent, hazard ratio [HR], 0.81, 95 percent confidence interval [CI], 0.66–1.00; p=0.045) after a median follow-up of almost 4 years. [ASCO 2017, abstract LBA500]
At 3 years, the estimated rate of invasive disease-free survival was 94.1 and 93.2 percent in the trastuzumab plus pertuzumab and trastuzumab only groups, respectively.
Patients with node-positive disease appeared to incur better outcomes with the addition of pertuzumab with 92 percent being disease-free at 3 years compared with 90.2 percent of patients on trastuzumab only (HR, 0.77, 95 percent CI, 0.62–0.96; p=0.019). In contrast, there was little effect on disease-free survival among those with node-negative disease at 3 years (97.5 percent vs 98.4 among patients on pertuzumab plus trastuzumab vs trastuzumab only, HR, 1.13, 95 percent CI, 0.68–1.86; p=0.64).
Women who were hormone receptor-negative and given pertuzumab also had a borderline significant benefit in terms of disease-free survival over women on trastuzumab only (92.8 percent vs 91.2 percent, HR, 0.76, 95 percent CI, 0.56–1.04; p=0.085).
The incidence of cardiac endpoints was similar between both groups (0.7 percent vs 0.3 percent in patients on pertuzumab plus trastuzumab vs trastuzumab only), while incidence of grade ≥3 diarrhoea was more common among patients on pertuzumab plus trastuzumab compared with trastuzumab only (9.8 percent vs 3.7 percent).
“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 von Minckwitz.
“Continuous follow-up is crucial for this study and is pre-planned for up to 10 years. The next analysis will be time-driven in 2.5 years,” he said.
“We learned from the CLEOPATRA** study that the addition of pertuzumab to chemotherapy and trastuzumab improved survival [in the metastatic setting],” said discussant Dr Carey Anders from the University of North Carolina at Chapel Hill, North Carolina, US.
One can consider the addition of pertuzumab in high-risk HER2-positive patients, specifically those with lymph node-positive disease or hormone receptor-negative disease, she said.
“To be clear, APHINITY is a positive trial. To be equally clear, as compared with results of studies of pertuzumab in the context of metastatic disease and neoadjuvant therapy, APHINITY is a disappointment,” said Dr Kathy D. Miller from the Indiana University School of Medicine in Indiana, US, in a commentary. [N Engl J Med 2017;doi:10.156/NEJMe1706150]
“[The] potential increase in cardiac toxic effects, with their attendant long-term consequences requires greater attention,” she said, stressing that the APHINITY trial should be the last of its generation due to the infeasibility of adding therapies for all HER2-positive patient on the “basis of anatomy”.