Fam-trastuzumab deruxtecan-nxki (Enhertu®)

Fam-trastuzumab deruxtecan-nxki (Enhertu®) is a targeted cancer therapy. It focuses on specific mutations found in human epidermal growth factor receptor 2 (HER2).^1-3

People with non-small cell lung cancer (NSCLC) may have changes to the HER2 gene that are called activating mutations. HER2 is thought to be activated in 3 possible ways:^1-3

1. Genetic mutation – a change in the DNA sequence of the gene
2. Gene amplification – an increase in the number of copies of a gene
3. Protein overexpression – the production of too much protein for which the gene codes

In August 2022, the US Food and Drug Administration (FDA) approved fam-trastuzumab deruxtecan-nxki for use in adults with NSCLC and activating HER2 mutations. It was granted accelerated approval for people whose NSCLC:^1,2

• Has spread
• Cannot be removed with surgery
• Has been previously treated

Accelerated approval of a treatment is often given for health conditions with few other treatment choices.⁴

NSCLC accounts for about 85 percent of all lung cancers. But only about 3 percent of these have activated HER2 mutations. This is the first FDA approval of a treatment for HER2-mutated lung cancer. It happened along with the approval of 2 related tests that look for activated HER2 mutations.^3,5

What are the ingredients in fam-trastuzumab deruxtecan-nxki?

Fam-trastuzumab deruxtecan-nxki has 2 active agents: trastuzumab and deruxtecan.⁶

How does fam-trastuzumab deruxtecan-nxki work?

Fam-trastuzumab deruxtecan-nxki is an antibody-drug conjugate (ADC). This means it has 2 main working parts. The first working part is a monoclonal anti-HER2 antibody called trastuzumab. This part seeks out and binds to mutated HER2 on the surface of a cancer cell. The second part is a cancer cell destroying agent called deruxtecan.⁶

Trastuzumab and deruxtecan are connected by a linker molecule that breaks apart after the trastuzumab binds to the mutated HER2. After the deruxtecan enters the cell, it damages the cell's DNA. This triggers a process called cellular death.^6,7

After destroying a cancer cell, deruxtecan keeps working. Once the first cell is killed and its outer layer (membrane) breaks down, the deruxtecan moves to a nearby cell. The drug then enters that cell, damages its DNA, and again triggers its death. This is called the bystander effect.^6,7

Because the trastuzumab antibody brings deruxtecan directly to specific cancer cells, this is called a targeted therapy. Targeted therapies are meant to affect as few healthy cells as possible. Overall, they are less hard on the body than systemic chemotherapy can be.^6,7

What are the possible side effects?

Common side effects of fam-trastuzumab deruxtecan-nxki include:^6,8

• Nausea and/or vomiting
• Fatigue
• Decreased appetite
• Diarrhea
• Constipation
• Loss of hair
• Heartburn
• Nose bleeding
• Headache
• Muscle and/or bone pain
• Numb or tingling hands or feet
• Skin rash

Other common side effects include a decrease in:⁶

• White blood cell count
• Hemoglobin
• Neutrophil count
• Lymphocyte count
• Platelet count
• Potassium levels

Fam-trastuzumab deruxtecan-nxki has a boxed warning, the strictest warning from the FDA. It has this warning because people who take this drug have a risk of developing severe lung problems including interstitial lung disease (ILD) and pneumonitis.⁶

ILD and pneumonitis can be life-threatening. Tell your doctor right away if you experience any of the following symptoms:⁶

• Cough
• Shortness of breath
• Fever
• Other breathing problems, like wheezing or chest tightness

Fam-trastuzumab deruxtecan-nxki also has a boxed warning because it can damage an unborn baby. Before taking fam-trastuzumab deruxtecan-nxki, talk to your doctor if you think you may be pregnant, want to become pregnant, or are not using contraception. This drug also is not recommended for use when breastfeeding.⁶

These are not all the possible side effects of fam-trastuzumab deruxtecan-nxki. Talk to your doctor about what to expect when taking fam-trastuzumab deruxtecan-nxki. You also should call your doctor if you have any changes that concern you when taking this drug.

Other things to know

Fam-trastuzumab deruxtecan-nxki is given as an intravenous infusion. Your doctor will determine the amount of fam-trastuzumab deruxtecan-nxki you need.⁶

Use of this drug may cause a heart condition called left ventricular dysfunction. Call your doctor if you experience any of the following signs of this condition:⁶

• New or worsening shortness of breath
• Cough
• Fatigue
• Swelling of ankles or legs
• Abnormal heartbeat
• Dizziness
• Sudden weight gain
• Sudden loss of consciousness

Before beginning treatment for NSCLC, tell your doctor about all your health conditions, including any history of heart problems or infections. Also tell them about any other drugs, vitamins, or supplements you are taking. This includes over-the-counter drugs.

For more information, read the full prescribing information of fam-trastuzumab deruxtecan-nxki.