Treatment Options for People with HER2-Mutant Non-Small Cell Lung Cancer (NSCLC)

Sponsored by Daiichi Sankyo and AstraZeneca

Lung cancer is the second most common type of cancer in the United States (U.S.). With more than 238,000 new diagnoses and 127,000 deaths from the disease estimated in 2023,¹ it is the leading cause of cancer-related death in the U.S.

NSCLC is the most common type of lung cancer and accounts for 80% to 85% of all lung cancer cases, while small cell lung cancer (SCLC) accounts for 10% to 15%.¹ As with many types of cancer, lung cancer may be more effectively treated if found at an early stage.² However, symptoms often go undetected or are mistaken for other common conditions, such as asthma, allergies or bronchitis. As a result, approximately half of all lung cancers are not diagnosed until they reach an advanced stage.³ The outlook for these patients tends to be worse because the disease has likely already spread – or metastasized – from the lungs to other parts of the body.

Biomarkers: Opening the door to more targeted treatment

Ways to treat NSCLC continue to be investigated. Research shows that certain biomarkers – genes or proteins found in or on tumors – can inform how quickly cancer cells may spread or respond to certain types of treatment.⁴ Thus, scientists are exploring potential therapies that specifically target biomarkers to slow cancer cell growth. These types of treatments are part of a category of medicines known as targeted therapies that have helped improve prognoses for certain patients with NSCLC, including metastatic disease.⁵ However, many patients still need additional options.

“While we have made progress identifying a number of biomarkers that may respond to targeted therapies, there is still an unmet need in patients with non-small cell lung cancer,” said Benjamin Levy, MD, Clinical Director of Medical Oncology, Johns Hopkins Sidney Kimmel Cancer Center, Sibley Memorial Hospital and Associate Professor, Johns Hopkins School of Medicine. “Ongoing research in non-small cell lung cancer is helping us find additional therapeutic targets, which helps to expand treatment options for these patients.”

Filling a critical treatment gap

Human epidermal growth factor receptor 2, known as HER2, is a protein found naturally in the human body and can play a role in the development of several types of cancers. HER2 (ERBB2) mutations (an abnormal change in the HER2 gene) are present in about 2% to 4% of people with NSCLC. Those who harbor HER2 mutations tend to be female, younger, and have a history of light or never smoking.^6,7 Research has shown that individuals carrying a HER2 mutation often have a poorer prognosis and a higher incidence of brain metastases compared to those with other types of NSCLC.⁸

Previously, no HER2-targeted therapies existed for these patients. That changed in August 2022 when the U.S. Food and Drug Administration (FDA) granted accelerated approval for ENHERTU^® (fam-trastuzumab deruxtecan-nxki) to treat adults who have NSCLC that has a certain mutation in the HER2 gene and cannot be removed by surgery (unresectable) or has spread to other parts of the body (metastatic), and who have received a prior treatment. ENHERTU was FDA approved for this use based on results from the DESTINY-Lung02 phase 2 trial, which measured how many patients responded, known as objective response rate (ORR), and how long they responded, known as duration of response (DOR). ENHERTU, a targeted treatment called an antibody-drug conjugate, or ADC, is still being studied to confirm these results. ENHERTU is designed to work differently than traditional chemotherapy, as it is made up of an antibody with chemotherapy attached. The antibody part of ENHERTU targets and attaches to HER2 on the cancer cell. ENHERTU then enters the cancer cell and chemotherapy is released, helping destroy the cancer cell, as well as other cells nearby.

“The FDA approval of ENHERTU for patients with HER2-mutant metastatic non-small cell lung cancer was great news for patients whose lung cancer harbors this gene,” said Dr. Levy. “Once again, we have witnessed a treatment option specifically targeting the underlying cause of the disease in lung cancer, offering patients the potential for improved outcomes if they progress on earlier lines of treatment.”

The DESTINY-Lung02 trial included 101 adult patients who received ENHERTU at 5.4 mg/kg. These patients were diagnosed with HER2-mutant unresectable or metastatic NSCLC and who received a prior treatment. The trial only evaluated ENHERTU and did not evaluate its results compared to another treatment option.

In the trial, ENHERTU shrank tumors for nearly 58% of patients (30 of 52). Additionally, half of trial participants who responded to ENHERTU continued to respond nearly 9 months later.

ENHERTU can cause serious side effects, including lung problems that may be severe, life-threatening or that may lead to death. Patients should tell their healthcare provider right away if they have any of the following symptoms: cough, trouble breathing or shortness of breath, fever and/or other new or worsening breathing problems. An HCP may reduce a patient's dose, delay treatment or completely stop treatment with ENHERTU if a patient experiences serious side effects.

The most common side effects of ENHERTU when used at the 5.4 mg/kg dose include nausea, low white blood cell count, low red blood cell count, feeling tired, low platelet counts, increased liver function tests, vomiting, hair loss, constipation, muscle or bone pain, decreased appetite, low levels of blood potassium, diarrhea and stomach-area pain.

ENHERTU can also cause harm to an unborn baby. Patients should tell their HCP right away if they become pregnant or think they might become pregnant, and both males and females should use effective contraception as instructed by their healthcare provider.

Please see Important Safety Information below.

What people with lung cancer or their loved ones can do

Those who have been diagnosed with lung cancer or their loved ones should ask their physicians about comprehensive biomarker testing. Researchers continue to explore new biomarkers and ways of treating different forms of the disease. If results show the presence of a HER2 gene mutation, it’s important that patients and caregivers talk to their care team to see if ENHERTU may be appropriate.

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 healthcare 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 (such as chest tightness, wheezing)

Low white blood cell counts (neutropenia). Low white blood cell counts are common with ENHERTU and can sometimes be severe. Your healthcare provider will check your white blood cell counts before starting ENHERTU and before starting each dose. Tell your healthcare 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 healthcare provider will check your heart function before starting treatment with ENHERTU. Tell your healthcare provider right away if you get any of the following signs and symptoms:

Your healthcare provider will check you for these side effects during your treatment with ENHERTU. Your healthcare 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 healthcare 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 healthcare 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 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 4 months after the last dose.

Before you receive ENHERTU, tell your healthcare 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 healthcare 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 healthcare provider will decide how many treatments you need.
• Your healthcare provider will give you medicines before your infusion to help prevent nausea and vomiting.
• Your healthcare 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 healthcare 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 at the 5.4 mg/kg dose include:

ENHERTU may cause fertility problems in males, which may affect the ability to father children. Talk to your healthcare 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 to treat adults who have:

• Non-small cell lung cancer (NSCLC) that has a certain mutation in the HER2 gene and cannot be removed by surgery or has spread to other parts of your body (metastatic), and who have received a prior treatment. Your healthcare provider will perform a test to make sure ENHERTU is right for you.
  • ENHERTU was FDA approved for this use based on a clinical study that measured how many patients responded and how long they responded. ENHERTU is still being studied to confirm these results.

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

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

Visit ENHERTU.com to learn more.

PP-US-ENL-0308
06/24

¹ American Cancer Society. Key Statistics for Lung Cancer. Accessed September 2023.

² American Cancer Society. Can Lung Cancer Be Found Early? Accessed September 2023.

³ SEER Survival Statistics. Accessed September 2023.

⁴ American Cancer Society. Biomarker Tests and Cancer Treatment. Accessed September 2023.

⁵ Xiao Y, et al. Frontiers in Pharmacology. 2023;14(1125547).

⁶ Liu L, et al. Clin Cancer Res. 2018;24(11):2594-2604.

⁷ Pillai R, et al. Cancer. 2017;1;123(21):4099-4105.

⁸ Offin M, et al. Cancer. 2019;125:4380-7.