Targeted Drug Therapy
Like chemotherapy, targeted therapies are drug therapies, but they are often given over a longer period of time.
These medicines are different from most chemotherapy drugs because they attack specific elements of the cancer cells and are less likely to harm normal cells.
There are five targeted therapy drugs publicly funded in New Zealand (see below).
Many targeted therapy drugs are given intravenously and you may have a special device called a port-a-cath inserted into your chest wall or a PICC line in your arm to help medical staff give these drugs easily on a regular basis. This will save a nurse having to find a vein in your arm or hand each time you need treatment.
New targeted therapies are being developed all the time and clinical trials are underway to investigate the effectiveness of these newer drugs. See below information about targeted therapies not yet funded in New Zealand and find out more about access to new medicines here.
Targeted therapies available in New Zealand
Herceptin (generic name: trastuzumab). This drug is used in women with HER2-positive breast cancer and works by blocking the chemical signals that tell this type of cancer cells to grow. Herceptin is a monoclonal antibody drug, designed specifically to target and block a particular molecule - in this case, the HER2 protein.
It is given by injection over a 12-month period and is now fully subsidised in New Zealand, thanks to a prolonged campaign by BCAC and others.
Side-effects: Herceptin is usually extremely well tolerated with any side effects being very rare. Very few women may experience flu-like symptoms, but these should become less severe as your treatment programme progresses.
In some cases, Herceptin can cause heart problems. This can range from very mild heart damage which results in no symptoms to more serious problems and in rare cases heart failure. Your doctor will discuss these issues with you and monitor your heart during your treatment programme. If you experience shortness of breath or heart palpitations let your doctor know immediately.
Biosimilar versions of Herceptin (trastuzumab) have now been developed as well. These molecules are not identical to Herceptin, but are designed to perform in the same way. They are not yet available in New Zealand, but because they are likely to be cheaper than the original drug, it is very likely that PHARMAC will soon tender for biosimilar trastuzumab to substitute for the original Roche product.
Tykerb (generic name: lapatinib) is a tyrosine kinase inhibitor fo the treatment of advanced HER2-positive breast cancer. This drug is given in pill form and fights HER2-positive breast cancer by attacking the HER2 protein at a different site from Herceptin. Clinical trials have shown lapatinib to be beneficial in advanced HER2-positive breast cancer and trials are now underway to see if, when combined with Herceptin, Tykerb could be of benefit in treating early breast cancer.
Tykerb is funded in New Zealand only for those with advanced HER2-positive breast cancer who have not already received trastuzumab (Herceptin) for their advanced disease (i.e. as a first-line treatment only). However, in other countries lapatinib is approved for later-line use for those whose advanced breast cancer has progressed on trastuzumab. This drug is not approved in New Zealand for the treatment of early stage HER2-positive breast cancer.
Side-effects: The most common side effects of Tykerb are diarrhoea, skin rash, vomiting and fatigue. Dosages can be adjusted and other medicines used to ease these problems. In rare cases Tykerb can result in minor heart damage.
Perjeta (generic name: pertuzumab). This monoclonal antibody drug is used in conjunction with Herceptin (trastuzumab) in patients with HER2-positive metastatic breast cancer who have not received prior therapies for their metastatic disease (i.e. as a "first-line treatment"). It works by inhibiting different proteins that cause HER2-positive breast cancers to grow. Results from the CLEOPATRA clinical trial reported in October 2014 showed an extraordinary survival benefit of 15.7 months for patients who received this drug. Perjeta is Medsafe registered and publicly funded in New Zealand for many HER2-positive metastatic breast cancer patients. The most common side-effects of Perjeta are diarrhoea, nausea, fatigue and rash.
Click here for a fact sheet on Perjeta.
Kadcyla (generic name: ado-trastuzumab emtansine or T-DM1). This drug is used in patients with HER2-positive advanced (or metastatic) breast cancer who have received prior trastuzumab and chemotherapy separately or together and either received prior therapy for metastatic disease or who relapsed within 6 months of completing adjuvant therapy. As it is used after earlier treatments for advanced disease it is known as a "second-line" strategy. Kadcyla is an antibody-conjugate drug that combines a chemotherapy drug (emtansine or T-DM1) that disrupts cell division, growth and functioning, with trastuzumab (Herceptin). Herceptin targets the T-DM1 to the HER-2-positive tumors, delivering the toxin directly to the tumour cells and reducing effects on other normal cells in the body. Results from the 2017 international clinical trial EMILIA showed patients receiving Kadcyla had a median overall survival benefit of 5.8 months (30.9 months vs. 25.1 months) compared to those given the combination of Xeloda (capecitabine) and Tykerb (lapatinib). This drug is approved by Medsafe and is publicly funded in New Zealand. Common side effects with Kadcyla may include tiredness, nausea and muscle/joint pain.
Recent data from the KATHERINE international clinical trial has shown that Kadcyla can also significantly reduce the risk of recurrence of invasive breast cancer (and death) when given to patients with early HER2-positive breast cancer whose tumours have not responded completely to neo-adjuvant (pre-surgery) chemotherapy and Herceptin treatment. Kadcyla is not funded for this use in New Zealand, but an application for this purpose from supplier Roche is currently being considered by PHARMAC (June 2020).
Click here to read a fact sheet on Kadcyla.
Ibrance® (generic name: palbociclib). This drug is one of a group called CDK 4/6 inhibitors - others are Kisqali® (generic name: ribociclib) and Verzenio® (generic name: abemaciclib). These drugs work by inhibiting particular enzymes that are needed for tumour cells to divide; they interrupt the ‘cell cycle’ and stop the tumours from growing. Ibrance is used for treating advanced (metastatic) oestrogen- receptor-positive, HER2-negative breast cancer. In New Zealand Ibrance is funded for first-, second- or later-line use in these patients. The PALOMA-3 clinical trial showed that adding Ibrance to Faslodex (fulvestrant) as a second-line treatment for patients who had previously responded to endocrine therapy prolonged overall survival by 6.9 months. This second- or later-line combination of Ibrance with Faslodex is funded for suitable patients in New Zealand. Ibrance comes in pill form. Common side effects include anaemia, fatigue, nausea, diarrhoea, vomiting, mouth sores and hair thinning.
Click here to read a fact sheet on Ibrance.
This group of drugs has shown promising results in trials with women who have triple-negative breast cancer and/or hereditary breast cancer caused by mutations to the BRCA1 and BRCA2 genes. PARP inhibitors are also useful for some types of ovarian cancer which are associated with BRCA gene mutations. Some examples of PARP inhibitors are: niraparib (Zeluja®), olaparib (Lynparza®), rucaparib (Rubraca®), talazoparib (Talzenna®) and veliparib.
A PARP is an enzyme which repairs everyday damage done to our DNA, but it also repairs cancer cells damaged by chemotherapy drugs. PARP inhibitors stop the PARP enzyme from repairing damaged cancer cells and thus allow chemotherapy drugs to work more effectively.
Several PARP inhibitors are being tested in clinical trials, but so far only olaparib (Lynparza) and talazoparib (Talzenna) have been commercialised for use against advanced HER2-negative breast cancer in women with BRCA mutations. In New Zealand, Lynparza is funded for treatment of ovarian cancer but not breast cancer.
AKT, mTOR and PI3K are three enzymes that interact in a signalling pathway that is vital for regulating normal cell proliferation. However, in many cancers this pathway is overactive leading to uncontrolled cell growth. Inhibitors of AKT, mTOR and PI3K can therefore be useful in treating cancer by bringing this process under control.
Most of the medicines in this group are currently in the clinical trial phase for the treatment of breast cancer. An exception is everolimus (Afinitor®), an mTOR inhibitor used overseas for treating hormone receptor positive, HER2-negative advanced breast cancer. BCAC applied to PHARMAC for funding for everolimus in 2018 but this was declined in 2019.
Current clinical trials include:
CAPTURE: A Phase II Australian study using alpelisib (PI3K inhibitor) as a later-line treatment for hormone receptor positive, HER2-negative advanced breast cancer that has returned after treatment with a CDK 4/6 inhibitor in patients who test positive for the PIK3CA mutation in a blood test (circulating tumour (ct) DNA test).
BYLieve: Phase II American trial of alpelisib with fulvestrant or letrozole for the treatment of PIK3CA mutant, hormone receptor positive, HER2-negative advanced breast cancer that has progressed on CDK 4/6 inhibitor therapy.
LOTUS: Final results from this Phase II international trial using ipatasertib (an AKT inhibitor) and paclitaxel for the treatment of metastatic triple negative breast cancer were presented in May 2020. Those receiving ipatasertib had median overall survival of 25.8 months compared to 16.9 months for those receiving only paclitaxel.
IPATunity170: Phase III follow-up to LOTUS, investigating ipatasertib plus the immunotherapy drug atezolizumab (Tecentriq®) plus paclitaxel for metastatic triple negative breast cancer.
INAVO120: Phase III trial of a PI3K inhibitor (GDC-0077) plus palbociclib plus fulvestrant for PIK3CA mutant, hormone receptor positive, HER2-negative locally advanced or metastatic breast cancer.
These drugs are synthesised monoclonal antibodies designed to lock on to specific molecular targets in our bodies. For example, atezolizumab (Tecentriq®) attaches to a protein called PD-L1, which normally acts as a ‘brake’ or ‘checkpoint’ on the immune system. In cancer, this checkpoint system is not always helpful as a stronger immune response can help to control the cancer. When atezolizumab blocks PD-L1, it unleashes the brake on the immune system, allowing it to attack the cancer cells. This anti-cancer strategy is often referred to as ‘checkpoint inhibition’. Tecentriq has been shown (in the Impassion130 clinical trial) to improve survival in patients with metastatic triple negative breast cancer whose tumours have high PD-L1 expression. Tecentriq is not PHARMAC-funded, but the supplier Roche has applied to PHARMAC for this and at present offers a Cost Share Programme (contact firstname.lastname@example.org for more information) (June 2020).
In recent years a number of innovative new medicines have become available for the treatment of early and advanced breast cancer. However, many of these medicines are not funded in New Zealand. Read more about these here and see our clinical trials page.