6 Years Follow-Up of Patients with Breast Cancer in the APHINITY Study
The primary analysis of results from the APHINITY clinical trial supported the combined anti-HER2 treatment with trastuzumab and pertuzumab in combination with chemotherapy in patients with early HER2-positive breast cancer. At the end of last year, efficacy and safety results of this treatment after more than 6 years of follow-up were presented.
Early Breast Cancer and Dual Targeting of HER2 Receptor
From November 2011 to August 2013, women with HER2-positive early operable breast cancer were enrolled in the APHINITY study. In the double-blind controlled study, they were randomized to either chemotherapy combined with trastuzumab and pertuzumab (2400 women) or chemotherapy combined with trastuzumab and placebo (2405 women). Patients were further stratified into arms based on the presence of disease in regional lymph nodes, hormone receptor expression, chemotherapy regimen, and geographical region of treatment.
Primary analysis results were published in the New England Journal of Medicine in 2017, leading to the approval of this combined anti-HER2 targeted treatment in patients with high recurrence risk with early-stage disease. It was found that patients with positive findings in regional lymph nodes derived significant benefit from the combination treatment (hazard ratio [HR] for achieving 3-year invasive disease-free survival [IDFS] 0.77; 95% confidence interval [CI] 0.62−0.96). At the time of the primary analysis, there were not enough data to validly assess overall survival. A preliminary analysis showed that mortality was similar in both treatment arms, and patients were continued to be monitored.
Effectiveness Results of the Combined Treatment
In mid-2019, after a median follow-up of 74.1 months, a planned interim data analysis was conducted. The number of deaths in both treatment arms did not significantly differ (5.2% for the pertuzumab arm vs. 6.1% for the placebo arm), with 6-year overall survival reaching 94.8% of women treated with pertuzumab and 93.9% of women receiving the combination with placebo.
There was a significant difference in the probability of IDFS – 6-year IDFS was achieved by 90.6% of women treated with pertuzumab and 87.8% receiving the combination with placebo (HR 0.76; 95% CI 0.64−0.91). Pertuzumab treatment reduced the occurrence of distant (5.9% vs. 7.7%) and locoregional (1.2% vs. 2.0%) recurrences of cancer.
The benefit of adding pertuzumab in patients with positive findings in regional lymph nodes was also confirmed. 6-year IDFS was achieved by 87.9% of women with positive findings and 83.4% with negative findings (HR for IDFS 0.72; 95% CI 0.59−0.87). Contrary to the primary analysis results, a clinical benefit also emerged in patients with hormone receptor expression positivity (HR for IDFS 0.73; 95% CI 0.59−0.92).
Safety of Dual Anti-HER2 Therapy
No new safety signals have been identified in the patient cohort since the primary analysis. A total of 18 primary cardiac events occurred in the pertuzumab-treated group and 8 events in the placebo group in the treatment combination. Primary events included heart failure (New York Heart Association [NYHA] III or IV), a 10-point drop in ejection fraction from study entry and simultaneously below 50%, or death from cardiac causes (heart failure, myocardial infarction, or primary arrhythmia). Secondary cardiac events were similarly frequent in both arms: 65 vs. 68 events. Secondary events were defined as asymptomatic or mildly symptomatic (NYHA II) reduction in ejection fraction confirmed by follow-up examination within 3 weeks.
Conclusion
Data obtained during the follow-up phase of the study confirm that adding pertuzumab to trastuzumab and chemotherapy is suitable for women with early HER2-positive breast cancer with the presence of tumor cells in regional lymph nodes. With increasing follow-up duration, it appears that the clinical benefit is not dependent on the presence or absence of hormone receptors. Another interim analysis is planned for the end of 2021.
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Source: Piccart M., Procter M, Fumagalli D. et al. Interim overall survival analysis of APHINITY (BIG 4-11): a randomized multicenter, double-blind, placebo-controlled trial comparing chemotherapy plus trastuzumab plus pertuzumab versus chemotherapy plus trastuzumab plus placebo as adjuvant therapy in patients with operable HER2-positive early breast cancer. San Antonio Breast Cancer Symposium, 10.‒12. 12. 2019. Available at: www.abstractsonline.com/pp8/#!/7946/presentation/2040
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