Intro text: 

A randomised, multicenter, double-blind, placebo-controlled comparison of chemotherapy plus trastuzumab plus placebo versus chemotherapy plus trastuzumab plus pertuzumab as adjuvant therapy in patients with operable HER2-positive primary breast cancer.

APHINITY has been testing whether adding a drug called pertuzumab to the standard adjuvant treatment (trastuzumab and chemotherapy) in patients with operable HER2-positive (HER+) primary breast cancer improves the outcome of patients with the disease.

Previous studies have shown that the use of the drug trastuzumab (Herceptin®) improves the chances of disease-free survival of patients with HER2+ breast cancer. This drug has been approved and licensed. It is now the standard of care to give trastuzumab along with chemotherapy after surgery for patients with HER2+ breast cancer.

However, up to 40% of patients with HER2+ breast cancer may become resistant to trastuzumab.

The aim of APHINITY is to investigate a new drug called pertuzumab, which also acts on the HER2 marker, but in a different way than trastuzumab, and to combine it with the current standard of care (chemotherapy and trastuzumab). This dual anti-HER2 therapy uses drugs that work in a complementary way and may improve treatment of this specific breast cancer subtype. The hope is that this strategy can overcome the resistance to treatment that occurs in some patients when a single drug is used.

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 the 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.

Patients aged 18 and older, with known hormone receptor status (estrogen receptor [ER] and progesterone receptor [PgR]), and confirmed HER2+ breast cancer. This means that the cells have been tested positive for a protein called HER2.
A total of 4,805 patients were recruited.

This study is conducted by BIG Headquarters, in collaboration with the Institut Jules Bordet – Clinical Trials Support Unit (IJB/CTSU) and Frontier Science Scotland (FSS), which serve respectively as independent data and statistical centres.

Pharmaceutical partner: Roche

24 research groups from the BIG network are participating in this trial.

Patients enrolled in APHINITY were randomly assigned to one of the following treatments:  
- Chemotherapy and trastuzumab combined with pertuzumab,
- Chemotherapy and trastuzumab with placebo.

The patients were treated for one year. The study will compare results between the two treatments, looking at the invasive disease free survival, overall survival, and safety.

During the trial, samples (blood and tumour tissue) have been collected from all participating patients and stored in the study biorepository for future research.

This will help us identify biomarkers, which can help to:
- predict response or toxicity (side effects) of the dual anti-HER treatment
- better understand the biology of HER2+ tumours
- develop and validate diagnostic tests

The last patient was recruited in August 2013.
All patients completed their one year of treatment and will be followed up for 10 years after the date the last patient was enrolled.

The trial is being conducted in 42 countries, with a total of 563 hospitals worldwide.  
290 of the participating hospitals are affiliated with the 24 participating BIG groups.

The trial is fully funded by Roche (sponsor). It was designed and conducted following BIG's Principles of Research Conduct.

ClinicalTrials.gov identifier: NCT01358877