Dr. Gunter von Minckwitz presents LBA500.
The APHINITY study randomly assigned 4,805 patients post-surgery with confirmed HER2-positive, early-stage breast cancer to standard adjuvant chemotherapy and trastuzumab plus placebo (2,405 patients) or pertuzumab (2,400 patients). In this study, the IDFS definition differed from the standardized definitions for efficacy endpoints (STEEP) in that it excluded second primary nonbreast cancers as an event, but the investigators used STEEP as a secondary endpoint, Dr. von Minckwitz said.
Overall, the 3-year rate of IDFS was 94.1% in the pertuzumab group and 93.2% in the placebo group, which was much higher than anticipated, Dr. von Minckwitz said.
“Treatment effect was homogenous throughout all subgroups; however, the node-positive and hormone receptor–negative cohorts appeared to derive the most benefit at the current point of time,” he said, “with a relative risk reduction of 23% and 24%, respectively, and a 3-year IDFS absolute increase of 1.8% and 1.6%, respectively.”
Preplanned subgroup analysis showed the number of invasive-disease events was low among patients with node-negative disease and no treatment effect was detectable (hazard ratio [HR] 1.13, 95% CI [0.68, 1.86]; p = 0.644).
In patients with node-positive disease, 139 patients (9.2%) in the pertuzumab group and 181 patients (12.1%) in the placebo group had invasive-disease events; the 3-year rate of IDFS was 92.0% in the pertuzumab group and 90.2% in the placebo group (HR for an invasive-disease event 0.77, 95% CI [0.62, 0.96]; p = 0.019).
In the cohort of patients with hormone receptor–negative tumors, 71 patients (8.2%) in the pertuzumab group and 91 patients (10.6%) in the placebo group had invasive-disease events (HR 0.76, 95% CI [0.56, 1.04]; p = 0.085); the 3-year rate of IDFS was 92.8% in the pertuzumab group and 91.2% in the placebo group.
In patients with hormone receptor–positive disease, 100 patients (6.5%) in the pertuzumab group and 119 patients (7.7%) in the placebo group had invasive-disease events (HR 0.86, 95% CI [0.66, 1.13]; p = 0.277); the 3-year rate of IDFS was 94.8% in the pertuzumab group and 94.4% in the placebo group.
Cardiac toxicity was low and not statistically significant. The largest adverse event was diarrhea (9.8% with pertuzumab and 3.7% with placebo), but this occurred most often with docetaxel, carboplatin, and trastuzumab. There was no difference in quality of life between the two groups. The next time-driven analysis will be in 2.5 years, Dr. von Minckwitz said.
Is More Better?
The HR “illustrates a 20% reduction in disease recurrence, with an absolute benefit of 1.7% at 4 years of follow-up,” discussant Carey K. Anders, MD, of the University of North Carolina at Chapel Hill Lineberger Comprehensive Cancer Center, said. From a financial perspective, she said 1 year of trastuzumab is about $55,000 (based on Medicare estimates).
“The addition of pertuzumab is an excess of nearly $100,000,” she said. “For our higher-risk, node-positive or node-negative patients, we may consider dual HER2-targeted therapy in combination with chemotherapy.”
During a question-and-answer period, a session attendee stated that the cost of adding pertuzumab in 100 patients would equate to $1 million, yet only two patients would be likely to benefit. Calling this an “insightful and realistic” interpretation of the data, Dr. Anders said the next step should be to determine “if we’re really seeing these incremental improvements in the patients with very high-risk disease. ‘Consideration’ is not an absolute term; I think we’re all struggling with this.”
Biomarker development should be able to help clinicians more accurately determine which patients, if any, would benefit most from additional therapy.
–Michelle Dalton, ELS