HER2-Mutant NSCLC Treatment Side Effects and How To Manage Them

Living with HER2-mutant non-small cell lung cancer (NSCLC) can take its toll. And while treatments can help slow the spread of the disease, they can come with their own challenges. Feeling sick, tired or unlike yourself can be discouraging.

But there’s hope: Many side effects are manageable.

“Treating HER2-mutant NSCLC isn’t just about living longer, it’s about living well,” says thoracic oncologist Lukas Delasos, DO. “That means managing your symptoms and adjusting your treatment plan when needed so you can maintain a high quality of life.”

Dr. Delasos shares what you may expect from common treatments and how to feel your best while navigating them.

Managing chemotherapy side effects

Chemotherapy is often part of first-line treatment for HER2-mutant NSCLC. It works by killing fast-growing cells — including cancer cells — throughout your body.

Chemo has a reputation for coming with a host of side effects. But Dr. Delasos points out that the chemo used for HER2-mutant NSCLC is often less intense than people fear.

“I call it ‘chemo-light,’” he says. “The regimens we use are generally well tolerated. Most patients keep their hair, and we give medications before and after chemo to help manage symptoms.”

Even still, chemo treatments can lead to side effects like:

• Nausea, vomiting, diarrhea or constipation
• Fatigue
• Anemia, which can lead to bruising, weakness and feeling short of breath
• Tingling or numbness in your hands and feet

To help combat those troubles, Dr. Delasos recommends:

• Taking prescribed anti-nausea medications as directed
• Resting when needed, but staying active as tolerated
• Letting your provider know about any new tingling or numbness
• Lowering your risk of infection by practicing proper hand hygiene and considering wearing a mask in big crowds

Managing immunotherapy side effects

Immunotherapy helps your immune system recognize and attack cancer cells. In HER2-mutant NSCLC, it's often used alongside chemotherapy.

“These medications help your body see the cancer and fight back — but they can also cause inflammation in healthy tissues,” Dr. Delasos explains.

In some cases, that can lead to autoimmune-like conditions, where your immune system attacks healthy tissue. Immunotherapy side effects can include:

• Skin rashes
• Fatigue
• Diarrhea
• Inflammation of organs like the colon, thyroid or lungs (rarely)

To keep these side effects manageable, Dr. Delasos urges you to report side effects early so they don’t escalate. Also:

• Let your team know about any new or unusual symptoms.
• Ask about medications to manage inflammation, if needed.
• Stay hydrated
• Rest when you need to.

Managing trastuzumab deruxtecan (Enhertu) side effects

If your cancer progresses after first-line treatment, your care team may recommend Enhertu® — a targeted infusion therapy that delivers chemotherapy directly to HER2-positive cancer cells.

When taking this medication, you may experience side effects like:

• Nausea, vomiting, diarrhea
• Low blood counts
• Interstitial lung disease (lung inflammation)

“Tell your provider right away about any new breathing problems, cough, fever or chest pain,” Dr. Delasos advises. “We want to catch lung inflammation early so we can treat it.”

This is what may help:

• Calling your care team if you have any respiratory symptoms
• Sticking to bland, easy-to-digest foods if your stomach feels off
• Staying hydrated
• Following your treatment schedule closely

Managing zongertinib (Hernexeos) side effects

Hernexeos® is another second-line option. It’s a pill that targets HER2 mutations, and many patients tolerate it well. In studies, it’s been shown to have very few side effects, but it may bring on some diarrhea and, occasionally, changes in liver function.

“I’ve had patients on zongertinib with minimal to no side effects — even at higher doses," Dr. Delasos relays. “We monitor labs and symptoms closely, just to be safe.”

If you take this medication:

• Report any GI symptoms to your care team.
• Keep track of how you feel over time.
• Keep up with regular lab checks to monitor your liver health.

The bottom line: Talk with your provider about side effects

If you’re experiencing side effects from HER2-mutant NSCLC — even if they seem small — let your care team know.

“We can hold or lower a dose, change medications or add support medications to help with side effects,” Dr. Delasos encourages. “You don’t need to suffer through treatment.”

Your treatment plan isn’t set in stone. And the more your providers know about how you’re feeling, the more they can help you feel better, faster.