Enhertu Plus Pertuzumab: New First-Line Option for Advanced HER2-Positive Metastatic Breast Cancer

Enhertu (fam-trastuzumab deruxtecan-nxki) is a type of targeted cancer treatment called an antibody-drug conjugate.The FDA has approved it in combination with another medicine, pertuzumab, as the first-line treatment for adults with HER2-positive breast cancer that has spread (metastatic) or cannot be removed with surgery (unresectable).This is the first new first-line treatment for this aggressive type of breast cancer in more than 10 years.The FDA has also approved specific tests to identify patients with HER2-positive breast cancer who are eligible for this treatment.Breast cancer is one of the most common cancers worldwide and a leading cause of cancer-related death.In the U.S., over 300,000 people are diagnosed with breast cancer each year, and more than 42,000 die from the disease.

Only about 3 in 10 patients with metastatic breast cancer live five years after diagnosis.

HER2-positive breast cancer makes up about 1 in 5 cases of breast cancer and tends to grow and spread faster than other types.

Each year, about 10,000 people in the U.S. start first-line treatment for this condition, but despite targeted therapies, most patients experience disease progression within two years.

Enhertu works by attaching a cancer-fighting drug to an antibody that targets the HER2 protein, which is present in high amounts on some cancer cells. This helps deliver the treatment directly to the cancer cells while limiting damage to healthy cells. Pertuzumab is a lab-made antibody that also targets the HER2 protein on cancer cells and blocks signals that help them grow and spread while also helping the immune system recognize and destroy those cancer cells. First approved in 2019, Enhertu is also approved for HER2-low and HER2-ultralow breast cancers and other HER2-positive solid tumors, including certain types of lung and stomach cancers.

Why Was It Approved?

The FDA approved Enhertu in combination with pertuzumab based on results showing it worked better than the current standard treatment for HER2-positive metastatic breast cancer. The clinical trial involved 1,157 people with HER2-positive unresectable or metastatic breast cancer who had not received prior treatment for metastatic disease. Patients receiving Enhertu plus pertuzumab lived significantly longer without their cancer worsening than those receiving the standard treatment THP (a combination of taxane, trastuzumab, and pertuzumab). Cancer progression was delayed for a median of 40.7 months with Enhertu plus pertuzumab compared with 26.9 months with THP, with the risk for disease progression or death reduced by 44% with the former. Tumors shrank in 87% of patients receiving Enhertu plus pertuzumab versus 81% receiving THP.

The side effects of Enhertu plus pertuzumab were similar to those already known for each drug, with no new safety issues identified. The most common side effects of the combination can include low blood counts, nausea, diarrhea, fatigue, hair loss, decreased appetite, weight loss, infections, muscle and bone pain, stomach-related problems, and liver enzyme changes (increased alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and bilirubin levels).

What Do I Need to Know?

Enhertu is given through an intravenous infusion every three weeks, usually at a dose based on your weight. When used with pertuzumab, the first dose of pertuzumab is higher, followed by lower doses in later treatments. Your health care provider will monitor you closely for serious side effects. One of the most serious risks is interstitial lung disease, a type of lung inflammation that can be life-threatening. If you have a cough, shortness of breath, or fever, tell your health care provider right away. Enhertu can also lower your white blood cell counts, which may raise your risk for infections. It may also affect your heart’s ability to pump blood. Your health care provider will check your blood counts and heart function regularly during treatment. Talk to your health care provider if you are pregnant or planning to become pregnant, as Enhertu may harm your fetus. You’ll need to use effective birth control during treatment and for several months (females for seven months and males for four months) after your last dose. Breastfeeding is not recommended while taking Enhertu and for at least seven months after your final dose. Also, tell your health care provider about all the medicines, including prescription and over-the-counter medicines, vitamins, and herbal supplements, you take.