Data from a 6-year analysis of the APHINITY trial showed that adding pertuzumab to the previous standard of trastuzumab plus chemotherapy after surgery continued to reduce the risk of recurrence and death in patients with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer. There were fewer deaths in patients treated with pertuzumab, although the survival benefit was not statistically significant at this time.
In its primary analysis, the APHINITY trial demonstrated that pertuzumab when added to adjuvant trastuzumab and chemotherapy statistically significantly (although modestly) improved invasive disease-free survival (iDFS) among patients with HER2-positive, operable breast cancer . Between November 2011 and August 2013, a total of 2,400 patients were randomly assigned to receive pertuzumab whilst 2,404 patients received placebo . The median follow-up was 45.4 months. In the intention-to-treat (ITT) population, the estimates of the 3-year iDFS rates were 94.1% for patients in the pertuzumab group and 93.2% for patients in the placebo group (HR 0.81; 95% CI 0.66-1.00; P=0.045). Patients with node-positive disease seemed to have a more pronounced benefit (HR 0.77; 95% CI 0.62-0.96) as was the case in patients with hormone receptor (HR)-negative disease (HR 0.76; 95% CI 0.56-1.04).
The second interim analysis of overall survival (OS) was conducted 2.5 years after the primary analysis when 50% of target events were anticipated. Median follow-up was 74.1 months; there were 272 deaths, which is 103 more than at the time of the primary analysis. Updated descriptive analyses of iDFS and cardiac safety were also performed and it was shown that there were 508 patients with an iDFS event (221 for pertuzumab-treated patients and 287 for placebo-treated patients), which is 127 more than at the time of the primary analysis.
Among the overall population, the OS was 94.8% for those receiving pertuzumab and 93.9% for those receiving placebo (HR 0.85; 95% CI 0.67-1.07; P=0.170). The time to a first iDFS event at 6 years was 90.6% and 87.8%, respectively (HR 0.76; 95% CI 0.64-0.91). The 6-year updated analysis further showed that among patients with node-positive disease, iDFS in the pertuzumab arm was 87.9% versus 83.4% in the placebo arm (HR 0.72; 95% CI 0.59-0.87), resulting in a 4.5% improvement. For node-negative patients, this was 95.0% versus 94.9%, respectively (HR 1.02; 95% CI 0.69-1.53). The treatment benefit of pertuzumab was also observed in the HR-positive cohort.
With regard to safety, it was show that diarrhoea (grade 3 or higher) occurred more frequently within the patients receiving pertuzumab (9.8%) versus patients in the placebo group (3.7%). No new cardiac safety issues emerged in this 74.1 months median follow-up: 0.8% of patients treated with pertuzumab experienced a primary cardiac event versus 0.3% of those treated with placebo. A secondary cardiac event occurred in 2.7% and 2.8% of patients, respectively. There were fewer deaths in the pertuzumab cohort than in the placebo cohort.
Researchers emphasise that follow-up is very important to determine the OS benefit of pertuzumab. They also stated that – according to these results – the benefit of pertuzumab in HER2-positive early breast cancer is maintained, with the greatest benefit continuing to be observed in the node-positive population. With longer follow-up, the benefit of pertuzumab no longer appears to depend on HR-status. Continued follow-up of patients will be conducted to determine a possible benefit for OS. A calendar-driven third interim OS analysis is planned in 2.5 years, and the event-driven final OS analysis is planned when 640 deaths have occurred.
1. Von Minckwitz G, et al. N Engl J Med. 2017;377:122-131.
2. Piccart M, et al. GS1-04. SABCS 2019.
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Table of Contents: SABCS 2019
Screening, Detection, and Diagnosis
Phase 2 Trial Update
Phase 3 Trial Update
Long-Term Study Results
Triple-Negative Breast Cancer
HER2-Positive Breast Cancer
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