To understand anti-HER2-targeted therapy for breast cancer, it is important to first understand what HER2 is, and what a positive HER2 means.
HER2 is a growth factor receptor on cells, the full name is called human epidermal growth factor receptor 2. It receives stimulatory messages from the body that accelerate tumor cell growth and division. HER2 positive means that breast cancer is more malignant and patients have a relatively poor prognosis. HER2 positive breast cancer accounts for about 20% of all breast cancers.
Trastuzumab, a targeted agent specifically for HER2, has been shown to significantly reduce the risk of death in HER2 positive breast cancer, providing a survival benefit to patients.
In recent years, multiple mechanisms of anti HER2 targeted drugs have emerged, and most clinical studies of new drugs in combination with trastuzumab have attempted to eliminate HER2 positive breast cancer cells through a “cascade of killers.
Pertuzumab is the successor to trastuzumab as an anti-HER2 target, and the National Comprehensive Cancer Network (NCCN) breast cancer guidelines state that the so-called “dual-targeted” therapy of pertuzumab in combination with trastuzumab is more effective than trastuzumab alone.
Why does pertuzumab work against cancer?
Pattuzumab is a monoclonal antibody that binds to HER2 at a different site than trastuzumab. Patuximab inhibits HER2 from heterodimerizing with other members of the HER family and is therefore more resistant to HER2.
Adjuvant therapy with patuximab improves disease-free survival by a small margin
The “dual-targeted” regimen of trastuzumab + patuximab has been a breakthrough in both postoperative treatment of HER2-positive advanced breast cancer and preoperative treatment of HER2-positive breast cancer. Can the combination continue to improve the long-term survival rate of postoperative breast cancer patients?
The APHINITY study sought to answer this question. This phase III study enrolled 4805 patients with HER2 positive breast cancer, half of whom received postoperative adjuvant therapy with pertuzumab + trastuzumab + chemotherapy.
The results showed that:
- Dual-targeted patients experienced disease recurrence in 7.1% of patients treated with dual-targeted therapy; compared with 8.7% of patients treated with single-targeted trastuzumab. Although the difference seems small, a scientific analysis found that patients treated with pertuzumab in combination with trastuzumab had a 19% lower risk of recurrence or death.
- At 3 years, 94.1% of patients treated with pertuzumab-based therapy did not experience breast cancer recurrence, compared with 93.2% of patients treated with trastuzumab in combination with chemotherapy.
- For lymph node-positive breast cancer, adding treatment with pertuzumab reduced the patient’s risk of recurrence or death by 23%. Because lymph node positivity is a high-risk factor, dual-targeted therapy has the potential to provide additional survival benefit for high-risk patients.
On December 2017 20 the United States approved patuximab for the adjuvant treatment of HER2 positive early-stage breast cancer.
How safe is patuximab?
In the APHINITY study, patients had a somewhat higher rate of moderate or higher adverse events during treatment with pertuzumab in combination with trastuzumab, with diarrhea, anemia, and neutropenia being the most common.
Compared with trastuzumab monotherapy, dual-targeted therapy did not significantly increase cardiotoxicity in patients, but the risk of other side effects, such as diarrhea, was slightly higher.
Pattuzumab in China
In 2018 January 2018, a marketing application for patuximab was submitted in China, but it has not yet been approved.
Currently, there are several clinical studies of pertuzumab for breast cancer underway in China (No. CTR20160366, CTR20131049, CTR20130952, CTR20150679, CTR20131487, etc.). We look forward to landing patuximab soon to provide more treatment options for breast cancer patients.
Summary
- For early stage HER2 positive breast cancer, trastuzumab monotargeted therapy combined with chemotherapy is effective. However, dual-targeted therapy with the addition of patuximab can further reduce the risk of recurrence and death in patients compared with monotargeted therapy.
- The dual-targeted regimen of patuximab + trastuzumab did not significantly increase cardiotoxicity in patients, but there was an increase in other side effects such as diarrhea and a slight increase in hematologic toxicity. It should be chosen with caution in patients with particularly poor health status.
- Targeted drugs are expensive, and the combination of two targeted drugs will increase the financial burden on patients.
Treatment of breast cancer has gotten better over the past decade or so, and anti-HER2 targeted therapy has been responsible for this. The imminent arrival of patuximab holds promise for continuing the treatment saga of trastuzumab in breast cancer.