As reported in the Journal of Clinical Oncology by Martine Piccart, MD, PhD, and colleagues, the preplanned second interim analysis of overall survival in the phase III APHINITY trial showed no significant benefit of the addition of adjuvant pertuzumab to chemotherapy plus trastuzumab after a median follow-up of 6 years in patients with early HER2-positive breast cancer. The invasive disease–free survival benefit observed with pertuzumab at the previously reported primary analysis persisted after long-term follow-up.
In the primary analysis, at a median follow-up of 45 months, the addition of pertuzumab to adjuvant trastuzumab and chemotherapy significantly improved invasive disease–free survival (hazard ratio [HR] = 0.81, P = .045), specifically in patients with node-positive or hormone receptor–negative disease.
Study Details
In the double-blind trial, 4,805 patients with node-positive or high-risk node-negative disease were randomly assigned to either 1 year of pertuzumab (n = 2,400) or placebo (n = 2,405) plus standard adjuvant chemotherapy and 1 year of trastuzumab. Chemotherapy consisted of either a sequential anthracycline/taxane regimen or docetaxel plus carboplatin for six cycles.
This analysis confirms the invasive disease–free survival benefit from adding pertuzumab to standard adjuvant therapy for patients with node-positive HER2-positive early breast cancer. Longer follow-up is needed to fully assess overall survival benefit.— Martine Piccart, MD, PhD, and colleagues
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Key Findings
Median follow-up was 74 months.
The second interim analysis of overall survival showed improvement with the addition of pertuzumab that did not reach the P = .0012 level required for statistical significance (HR = 0.85, P = .17). Rates at 6 years were 95% (125 deaths, 5.2%) in the pertuzumab group vs 94% (147 deaths, 6.1%) in the control group. The first interim analysis at the time of primary invasive disease–free survival analysis (median follow-up of 45 months) showed a hazard ratio of 0.89 (P = .47).
An updated invasive disease–free survival analysis yielded a hazard ratio of 0.76 (95% confidence interval [CI] = 0.64–0.91), with 6-year rates of 91% vs 88%.
In the updated analysis, the node-positive cohort (68% of all patients) continued to exhibit an invasive disease–free survival benefit from pertuzumab (HR = 0.72, 95% CI = 0.59–0.87), with 6-year rates of 88% vs 83%. No benefit was apparent in the node-negative cohort (HR = 1.02, 95% CI = 0.69–1.53), with 6-year rates of 95% in both groups.
In the updated analysis, hazard ratios for invasive disease–free survival favored the addition of pertuzumab: 0.83 (95% CI = 0.63–1.10) among patients with hormone receptor–negative disease (38% of all patients) and 0.73 (95% CI = 0.59–0.92) among those with hormone receptor–positive disease.
With the 2.5 additional years of follow-up since primary analysis, one additional primary cardiac event (heart failure) was observed in the pertuzumab group, and one additional secondary cardiac event was observed in each group. The rates of primary and secondary cardiac events during the entire follow-up in the pertuzumab vs control groups were 0.8% vs 0.3% and 2.7% vs 2.8%.
No new safety signals were identified.
The investigators concluded, “This analysis confirms the invasive disease–free survival benefit from adding pertuzumab to standard adjuvant therapy for patients with node-positive HER2-positive early breast cancer. Longer follow-up is needed to fully assess overall survival benefit.”
Dr. Piccart, of Institut Jules Bordet and L’Université Libre de Bruxelles, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by F. Hoffmann-La Roche Ltd/Genentech. For full disclosures of the study authors, visit ascopubs.org.
