APHINITY empowers pertuzumab’s use in adjuvant setting
The use of pertuzumab in the adjuvant setting significantly increases the rate of invasive-disease-free survival (IDFS) of persons with HER2+ early breast cancer (eBC).
The APHINITY trial provided concrete evidence for pertuzumab’s use in the adjuvant setting as patients in the pertuzumab arm exhibited significantly improved rates of IDFS among patients with HER2-positive
APHINITY was a multicenter, randomized, double-blinded, placebo-control trial which recruited patients with HER2-positive eBC who had their primary tumour surgically removed prior to randomization. Within 8 weeks of undergoing surgery, 4,805 women with HER2-positive primary breast cancer were randomized to undergo chemotherapy (both anthracycline and non-anthracycline regimens were allowed) for 18 weeks plus trastuzumab in addition to either pertuzumab (n=2,400) or placebo (n=2,405) for 52 weeks.
The primary outcome was IDFS (defined as the time from randomization to first occurrence of ipsilateral local or regional invasive breast cancer recurrence, distance recurrence, contralateral invasive breast cancer, or death from any cause. With a follow-up period of only 45 months, patients with high risk of recurrence, defined as those with lymph node-positive or hormone receptor-negative disease, derive the strongest benefit, with almost 25 percent reduction in risk of recurrence or death.
The incidence of invasive breast cancer was lower among patients on pertuzumab plus trastuzumab versus trastuzumab only (7.1 percent vs 8.7 percent, hazard ratio [HR], 0.81, 95% confidence interval [CI], 0.66–1.00; p=0.045) after a median follow-up of almost 4 years.
Glimpses of pertuzumab’s potential was already discussed in ASCO 2017, where lead author Dr Gunter von Minchwitz, president of the German Breast Group, Neu-Isenberg, Germany, was quoted as saying: “The advent of HER2-targeted therapy changed the outlook for women with HER2-positive breast cancer. Our early findings [in APHINITY] suggest that we may be able to further improve outcomes for some women by adding a second HER2-targeted treatment, without increasing risk of serious side effects.”
With evidence from APHINITY, various international expert groups have come out with new recommendations and guidelines to reflect the new evidence. The St. Galen Expert Consensus recommends dual blockage with pertuzumab and trastuzumab in patients who are at high risk of relapse due to lymph node involvement or hormone receptor negativity as it improves outcomes in these patients. The American Society of Clinical Oncology (ASCO) guidelines say clinicians may add 1-year adjuvant pertuzumab to trastuzumab-based combination chemotherapy in patients with high-risk, early stage, HER2-positive breast cancer. The German association of gynaecology and oncology (AGO) also recommends adjuvant trastuzumab and pertuzumab in HER2-positive early breast cancer in patients with node positive or hormone receptor negative disease.
In the US, pertuzumab received approval for use in the adjuvant setting in combination with trastuzumab and chemotherapy in patients with HER2-positive eBC and at high risk of recurrence in late 2017. Malaysia is due to receive the updated indication of pertuzumab’s use in the adjuvant setting in end December 2018.
The aim is to cure
The call for timely diagnosis and treatment in early breast cancer is to facilitate a cure. Hence, patients should be given the most efficacious treatment. However, one-in-four patients treated for HER2-positive eBC still go on to develop metastatic breast cancer and up to 78 percent of HER2-positive metastatic BD are due to eBC relapse.
There is currently no cure for HER2-positive metastatic breast cancer, extended treatment and disease burden translating into major economic implications. [Breast Cancer Res Treat 2012; 134:815–822] Although most patients will benefit from trastuzumab treatment, one-in-four will still experience recurrence or death despite 1 year of adjuvant therapy. Thus, the addition of pertuzumab into the adjuvant setting represents a significant improvement over existing treatment options.
*APHINITY: A study of pertuzumab in addition to chemotherapy and trastuzumab as adjuvant therapy in participants with HER2-positive primary breast cancer