Targeted therapies for metastatic breast cancer

Several targeted therapies for metastatic breast cancer are available in Australia. These are:

• HER2 targeted therapies
• antibody drug conjugates
• drugs such as CDK4/6 inhibitors, mTOR inhibitors, PIK3CA inhibitors.

Unfortunately, not all drugs are on the Pharmaceutical Benefits Scheme (PBS). They can be very expensive but you may be able to access them through a pharmaceutical access program. Read Ways to access new breast cancer drugs.

Talk to your treating team about the best treatment for your type of metastatic breast cancer.

HER2 targeted therapies

In HER2-positive metastatic breast cancer, targeted therapies block the action of HER2 receptors on cells. Multiple HER2 therapies are available:

• lapatinib (Tykerb)
• neratinib (Nerlynx - not on the PBS)
• pertuzumab (Perjeta)
• trastuzumab emtansine (Kadcyla, TDM-1)
• trastuzumab (Herzuma, Ritemvia, Rituzena, Tuxella, Ogivri, Ontruzant, Kanjinti, Trazimera)
• trastuzumab deruxtecan – T-DXd (Enhertu).

Once the cancer is controlled, HER2 therapy can keep the cancer under control for long periods of time.

Read About HER2 targeted therapies.

CDK4/6 inhibitors 

Metastatic breast cancer that is hormone receptor-positive, HER2-negative may be treated using CDK4/6 inhibitors.

These drugs include:

• abemaciclib (Verzenio)
• palbociclib (Ibrance)
• ribociclib (Kisqali).

A combination of CDK4/6 inhibitors and hormone-blockers (aromatase inhibitors or fulvestrant) can make treatment more effective.

As a first line treatment, they can double the time cancer the cancer is controlled, before it progresses, and can improve overall survival. These drugs allow good quality of life, with few serious side effects.

The CDK4/6 inhibitors are also available for second line treatment with fulvestrant. Fulvestrant can also be used on its own (as a ‘monotherapy’).

Read Treatments for HR+ metastatic breast cancer.

How CDK4/6 inhibitors work

CDK4/6 proteins are in healthy cells and cancer cells. They help control how quickly cells grow and divide.

In most oestrogen-receptor positive (ER+) breast cancers, CDK type 4 and 6 are found to be overactive. This causes the cells to grow and multiply more quickly.

A CDK inhibitor stops CDKs from being able to work in their usual way.

Antibody drug conjugates

Antibody drug conjugates are available for the treatment of metastatic breast cancer. These include:

• Sacituzumab govitecan (Trodelvy)
• Trastuzumab deruxtecan (Enhertu)
• Trastuzumab emtansine (Kadcyla)

In Australia, Trodelvy is currently (March 2025) approved for people who have had at least 2 previous systemic treatments (e.g. chemotherapy) for triple negative breast cancer. At least one of those treatments must have been for metastatic disease.

mTOR inhibitors

mTOR inhibitors are used to treat HR+ metastatic breast cancers.

Over time, cancer cells can become resistant to hormone-blocking therapy. An mTOR inhibitor, given with a hormone-blocking therapy, can overcome that resistance and make hormone-blocking therapy effective again.

This treatment is often considered when resistance is developing and chemotherapy looks like the next treatment option.

The mTOR inhibitor available in Australia is everolimus (Afinitor).

The combination of everolimus with the aromatase inhibitor exemestane has doubled how long the cancer is under control, before it progresses.

This combination treatment is subsidised by the PBS.

PARP inhibitors

PARP inhibitors can be effective for BRCA mutation-related metastatic breast cancer. They can be used alone or with chemotherapy. 

Olaparib (Lynparza) is an oral medication that people generally cope well with.

Other

Some drugs are available in Australia, but not on the Pharmaceutical Benefits Scheme. These include PI3K inhibitors such as alpelisib (Piqray) if a PIK3CA mutation is present.

You may be able to access them through:

• a clinical trial
• patient access schemes
• self funding (note: these medications can be very expensive). 

Find out Ways to access new breast cancer drugs.