Gastric cancer, which typically occurs when cancer cells form in the lining of the stomach, is the fifth most common cancer worldwide and fourth–leading cause of cancer death, according to the World Health Organization. According to the American Cancer Society, in the U.S., it is estimated that 26,560 new cases of gastric cancer were diagnosed in 2021 and more than 11,000 people died from the disease.Gastric cancer more commonly affects men over age 50.

The American Cancer Society estimates that about 1 in 5 gastric cancers are classified as HER2, or human epidermal growth factor receptor 2, positive. HER2 is a protein found on the surface of cells. While many types of cells have HER2 receptors, a person having HER2 positive gastric cancer means that the cancer cells have more HER2 receptors than normal. The number of HER2 receptors correlates with poorer outcomes and more aggressive disease.
“It is critically important to test tumors of patients with gastric cancer for HER2 and other biomarkers that may be present,” said Ronan Kelly, MD, MBA, director of the Charles A. Sammons Cancer Center and the W.W. Caruth, Jr. chair of immunology at Baylor University Medical Center. “Knowing this information will help physicians prescribe an appropriate treatment option to target their specific cancer, which may lead to better outcomes.”

Treatments for HER2 Positive Metastatic Gastric Cancer
The current first–line standard of care for patients with HER2 positive metastatic gastric cancer is a combination of chemotherapy plus trastuzumab. If their cancer progresses after first–line treatment, certain patients with HER2 positive advanced gastric cancer have a targeted option called an antibody drug conjugate (ADC) to help treat the disease. Comprised of an antibody with a chemotherapy attached, some ADCs work by targeting HER2 and binding to the HER2 positive cancer cell to help destroy it. The U.S. Food and Drug Administration approved ENHERTU® (fam–trastuzumab deruxtecan–nxki), an ADC, for the treatment of adult patients with stomach cancer called gastric or gastroesophageal junction (GEJ) adenocarcinoma that has spread to areas near your stomach (locally advanced) or that has spread to other parts of your body (metastatic), and who have received a prior trastuzumab–based regimen. Although it was designed to target HER2 positive cancer cells, ENHERTU may affect some healthy cells.

ENHERTU can cause serious side effects including lung problems that may be severe, life threatening or that may lead to death; low white blood cell count; heart problems that may affect your heart's ability to pump blood; or harm to an unborn baby. See Important Safety Information below.

“This is the first HER2–directed medicine in a decade for patients who previously had limited options,” Kelly said. “As someone who has treated gastric cancer for more than 20 years, I’m excited about the availability of another HER2–targeted therapy for this form of cancer – a therapy which has been shown to be more effective than standard chemotherapy (irinotecan or paclitaxel) for this patient population.”

Important Safety Information

What is the most important information I should know about ENHERTU?

ENHERTU can cause serious side effects, including:

Lung problems that may be severe, life–threatening or that may lead to death. If you develop lung problems your healthcare provider may treat you with corticosteroid medicines. Tell your health care provider right away if you get any of the following signs and symptoms:

• Cough
• Trouble breathing or shortness of breath
• Fever
• Other new or worsening breathing symptoms (e.g., chest tightness, wheezing)

Low white blood cell count (neutropenia). Low white blood cell counts are common with ENHERTU and can sometimes be severe. Your health care provider will check your white blood cell counts before starting ENHERTU and before starting each dose. Tell your health care provider right away if you develop any signs or symptoms of an infection or have fever or chills during treatment with ENHERTU.

Heart problems that may affect your heart’s ability to pump blood.  Your health care provider will check your heart function before starting treatment with ENHERTU. Tell your health care provider right away if you get any of the following signs and symptoms:

New or worsening shortness of breath Coughing Feeling tired Swelling of your ankles or legs

Irregular heartbeat Sudden weight gain Dizziness or feeling light–headed Loss of consciousness

Your health care provider will check you for these side effects during your treatment with ENHERTU. Your health care provider may reduce your dose, delay treatment or completely stop treatment with ENHERTU if you have severe side effects.

Harm to your unborn baby. Tell your health care provider right away if you become pregnant or think you might be pregnant during treatment with ENHERTU.

• If you are able to become pregnant, your health care provider should do a pregnancy test before you start treatment with ENHERTU.
• Females who are able to become pregnant should use effective birth control (contraception) during treatment with ENHERTU and for at least 7 months after the last dose.
• Males who have female partners that are able to become pregnant should use effective birth control (contraception) during treatment with ENHERTU and for at least 4 months after the last dose.

Before you receive ENHERTU, tell your health care provider about all of your medical conditions, including if you:

• Have lung or breathing problems.
• Have signs or symptoms of an infection.
• Have or have had any heart problems.
• Are breastfeeding or plan to breastfeed. It is not known if ENHERTU passes into your breast milk. Do not breastfeed during treatment with ENHERTU and for 7 months after the last dose.

Tell your health care provider about all the medicines you take, including prescription and over–the–counter medicines, vitamins, and herbal supplements.

How will I receive ENHERTU?

• You will receive ENHERTU into your vein through an intravenous (IV) line by your healthcare provider.
• ENHERTU is given 1 time every three weeks (21–day treatment cycle).
• Your health care provider will decide how many treatments you need.
• Your health care provider may slow down or temporarily stop your infusion of ENHERTU if you have an infusion–related reaction, or permanently stop ENHERTU if you have severe infusion reactions.
• If you miss a planned dose of ENHERTU, call your health care provider right away to schedule an appointment. Do not wait until the next planned treatment cycle.

What are the possible side effects of ENHERTU?

ENHERTU can cause serious side effects. See "What is the most important information I should know about ENHERTU?"

The most common side effects of ENHERTU, when used in people with stomach cancer, include:

Low red blood cell counts Low white blood cell counts Low platelet counts Nausea Decreased appetite Increased liver function tests Feeling tired

Diarrhea Low levels of blood potassium Vomiting Constipation Fever Hair loss

ENHERTU may cause fertility problems in males, which may affect the ability to father children. Talk to your health care provider if you have concerns about fertility

These are not all of the possible side effects of ENHERTU. Call your doctor for medical advice about side effects. You may report side effects to Daiichi Sankyo at 1–877–437–7763 or to FDA at 1–800–FDA–1088.

What is ENHERTU?

• ENHERTU is a prescription medicine used in adults to treat human epidermal growth factor receptor 2 (HER2)–positive stomach cancer called gastric or gastroesophageal junction (GEJ) adenocarcinoma that has spread to areas near your stomach (locally advanced) or that has spread to other parts of your body (metastatic), and who have received a prior trastuzumab–based regimen.

It is not known if ENHERTU is safe and effective in children.

Please see full Prescribing Information, including Boxed WARNINGS, and Medication Guide.

 

Sponsored by Daiichi Sankyo and AstraZeneca.

ENHERTU® is a registered trademark of Daiichi Sankyo Company, Limited.

©2021 Daiichi Sankyo, Inc. and AstraZeneca.

PP–US–ENG–0377
06/21

Photo courtesy of Getty Images (male patient)
Photo caption (headshot): Ronan Kelly, MD, MBA.