Two to three out of 10 breast cancer patients are positive for HER-2 (human epidermal growth factor receptor-2, which promotes cancer cell proliferation and increases tumor aggressiveness). Such patients have a more aggressive disease, are prone to recurrence and metastasis, have a short survival, and have a poor prognosis.
But the advent of HER-2 targeted therapy has greatly improved the long-term survival rate of HER-2-positive patients, and the drug can be used to treat both surgical and inoperable patients.
What are the HER-2-targeting drugs? How do they work?
Current HER-2-targeted drugs include the following categories:
- Monoclonal antibodies: such as trastuzumab, patuximab
- Small molecule inhibitors: e.g. lapatinib, pyrrolitinib;
- Antibody drug coupling agents: such as the new drug trastuzumab-metanephrine coupling T-DM1.
Trastuzumab is still the most clinically used. Trastuzumab, the “oldest” anti-HER-2 targeting agent, targets the HER-2 protein on tumor cells and inhibits tumor cell proliferation.
The current range of approved HER-2 targeting drugs is shown below.
Pre-operative neoadjuvant therapy
Preoperative neoadjuvant therapy with trastuzumab in combination with chemotherapy resulted in increased surgical success, reduced postoperative recurrence, and significantly longer patient survival compared with chemotherapy alone. Further studies also found that trastuzumab + pertuzumab combined with docetaxel, a chemotherapy agent, was more effective.
Postoperative adjuvant therapy
Postoperative adjuvant therapy with trastuzumab or patuximab in patients with HER-2-positive breast cancer reduces the relative risk of recurrence by 46% to 52% and the relative risk of death by about 33%. And the efficacy is better if trastuzumab combined with pertuzumab is used. Current guidelines in China recommend trastuzumab as the standard adjuvant therapy after surgery with a 1-year dosing cycle, and foreign guidelines recommend both drugs.
Late stage treatment
- Advanced first-line: a combination of trastuzumab and pertuzumab dual-target combination chemotherapy (docetaxel, paclitaxel, vincristine, capecitabine, etc.) is recommended; trastuzumab single-target combination chemotherapy is available if patients are unable to use pertuzumab because of the high price.
- Late second line: Results from two previous large clinical trials (EGF100151 and GBG26 studies) confirm that trastuzumab has a “reuse-effective” profile – Patients who were refractory to first-line trastuzumab were significantly prolonged in second-line refill with trastuzumab + chemotherapy, and second-line lapatinib (another HER-2 targeting agent) + chemotherapy was effective after refractory treatment.
- Post-resistance: lapatinib or pyrrolizumab in combination with capecitabine, and trastuzumab-metanephrine coupling T-DM1 monotherapy regimens are available in patients who have failed or are resistant to trastuzumab therapy.
How long do I need to use it?
Patients and families are concerned about the duration of HER-2-targeted drugs, considering relapse on the one hand, and the toxicity and resistance of the drugs on the other.
The duration of trastuzumab recommended by the Chinese Society of Clinical Oncology Breast Cancer (CSCO BC) guidelines:
- When patients receive trastuzumab in combination with chemotherapy before surgery, effective chemotherapy should last at least 6-8 weeks, and the duration of chemotherapy depends on both the tumor efficacy and the patient’s tolerance to chemotherapy.
- After surgery, the recommended standard duration of adjuvant trastuzumab therapy for patients with HER-2-positive breast cancer is 1 year.
- If patients achieve complete remission, the duration of HER-2-targeted therapy should be weighed against treatment toxicity, financial burden, and, in some patients, the possibility of suspending anti-HER-2 therapy for several years after complete remission and resuming treatment with previously beneficial anti-HER-2 agents after disease has progressed again.
- For patients who relapse after trastuzumab resistance, priority is given to continuing trastuzumab and switching to another chemotherapy agent if previous therapy was effective and discontinued for toxicity or financial reasons, or to switching to an anti-HER-2 agent if the patient progresses in therapy.
With the exception of trastuzumab, which has a standard duration of therapy, targeted agents used in multiple lines of therapy are generally used until the patient’s disease progresses or until an intolerable toxic reaction occurs.