APHINITY

Overcoming resistance to treatment and reducing the risk of invasive breast cancer returning.

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The APHINITY trial found that adjuvant pertuzumab in combination with trastuzumab and chemotherapy in patients significantly improved the rates of invasive-disease-free survival among patients with HER2-positive, operable breast cancer when it was added to trastuzumab and chemotherapy.

The APHINITY trial – involving 4,805 patients from 42 countries, recruited in 563 hospitals of which more than half were linked to 24 member groups– tested whether adding pertuzumab to the standard adjuvant treatment (trastuzumab and chemotherapy) in patients with operable HER2-positive primary breast cancer improved the outcome of patients with the disease. Indeed, previous studies including HERA, had shown that trastuzumab combined with chemotherapy improved the chances of disease-free survival for this category of patients, and is now the standard of care. However, 40% of patients with this subtype of breast cancer may become resistant to trastuzumab.

APHINITY analysed whether adjuvant pertuzumab – which also acts on the HER2 marker – in combination with trastuzumab and chemotherapy in patients was better than standard treatment. The study’s first results, presented at American Society of Clinical Oncology Annual Meeting 2017 and published in the New England Journal of Medicine that same year, found that this new dual anti-HER2 therapy regimen reduced the risk of breast cancer recurrence or death by 19% compared to trastuzumab and chemotherapy alone. At three years, 94,1% of patients treated with pertuzumab in combination with trastuzumab and chemotherapy did not see a breast cancer recurrence, compared to 93,2% of patients treated with trastuzumab and chemotherapy alone.

The first results of the APHINITY trial therefore showed a modest benefit from adding pertuzumab to trastuzumab, in itself an important step in advancing cancer care for patients – especially for women with the highest risk – those with node-positive and hormone-receptor negative breast cancer.

The updated results, presented at the San Antonio Breast Cancer Symposium 2019 and published in the Journal of Clinical Oncology in 2021, showed that, after six years of follow-up, the greatest benefit remained in patients at high risk of recurrence, such as those with lymph node-positive disease, but regardless of hormone receptor status. Although fewer deaths were seen among the patients who received treatment with pertuzumab, the data are still immature and have not shown definitive improvement in overall survival, which will be reviewed again at a next interim analysis.Over the course of the clinical trial, samples were collected from all participating patients for future research. These samples will help identify biomarkers, which can help to predict response or toxicity of the dual anti-HER treatment, and better understand the biology of HER2+ tumours as well as develop and validate diagnostic tests.

This trial, which completed recruitment and reported results much more quickly than planned despite its global reach and complexity, is an example of what can be achieved when BIG groups and their partners work together.  The trial is led by BIG and the Institut Jules Bordet – Clinical Trials Support Unit in collaboration with Roche.