How planning ahead, tracking symptoms, and leaning on your care team can keep you stay strong through treatment.

If you’ve been told you have HER2-positive colorectal cancer (HER2+ CRC), you’re part of a smaller group — only about 3–5% of people with metastatic CRC. But there’s good news: newer targeted therapies are changing what’s possible. Treatments like tucatinib + trastuzumab and trastuzumab deruxtecan (Enhertu®) are helping many patients live better and longer.

Of course, these powerful treatments can come with side effects — those curveballs that can disrupt your daily life or your ability to stay on therapy. The good news? With good preparation, early communication, and the right care team, you can often manage these bumps and keep pressing forward.

Think of it as learning to drive a manual car — you may stall early on, but once you know how, you stay in gear.

Side effects can feel discouraging, but knowing what to expect—and catching problems early—can make a huge difference. In many clinical trials, side effects are one of the top reasons people stop therapy early. But with close monitoring and good symptom management, many people are able to stay on treatment longer and maintain their quality of life.

For HER2+ CRC, the side effects most often reported include:

• Diarrhea
• Fatigue
• Skin reactions (rash, itching)
• Lung effects (interstitial lung disease, also called pneumonitis)

Paying attention to these symptoms isn’t just about comfort — it’s about giving these new therapies the best chance to work.

Trial: MOUNTAINEER (Phase II) — ClinicalTrials.gov: [NCT03043313]

ClinicalTrials.gov+2The Lancet+2
This trial evaluated tucatinib combined with trastuzumab in patients with HER2+ metastatic colorectal cancer who had already received other treatments. ClinicalTrials.gov+3The Lancet+3ScienceDirect+3

Key side effect numbers (from trial / prescribing material):

• Diarrhea (all grades) in about 64% of patients, with Grade 3+ diarrhea in about 6% ClinicalTrials.gov+5tukysahcp.com+5The Lancet+5
• Other common events: fatigue, rash, liver enzyme changes, nausea, infusion-related reactions The Lancet+3Cancer.gov+3tukysahcp.com+3
• About 6% of participants needed a drug dose reduction or stopped treatment due to side effects Cancer.gov+2The ASCO Post+2

What this means for patients:

Tucatinib + trastuzumab can be an effective next-line option for HER2+ CRC, but diarrhea and fatigue are common. Catching and treating these early can help keep treatment on track.

Regulatory status: This combination was FDA-approved in 2023 for HER2+ metastatic colorectal cancer. Cancer.gov+2The ASCO Post+2

A follow-up study, MOUNTAINEER-03, is now testing the combination with chemotherapy (mFOLFOX6) as a first-line option. ASCO Publications+1

Trial: DESTINY-CRC02 (Phase II) — ClinicalTrials.gov: [NCT04744831] The Lancet+4ClinicalTrials.gov+4The Lancet+4
This global study compared two doses (5.4 mg/kg vs. 6.4 mg/kg) of Enhertu® for patients with HER2-overexpressing metastatic CRC. The Lancet+4ClinicalTrials.gov+4Daiichi Sankyo+4

Key side effect & efficacy numbers (as reported):

• Nausea: ~ 63% of patients ASCO Publications+2ASCO+2
• Fatigue: ~ 49% ASCO Publications+2ScienceDirect+2
• Appetite loss: ~ 29% ASCO Publications+1
• Interstitial Lung Disease (ILD) / pneumonitis: ~ 8.2% overall (with about 1.1% fatal cases) ASCO Publications+2The Lancet+2
• In the 6.4 mg/kg arm, there was a grade 5 (fatal) ILD event reported. The Lancet+3ASCO Publications+3ScienceDirect+3

What this means for patients:
Enhertu® has shown promising results in HER2+ CRC, but ILD is a rare yet serious side effect. If you notice new coughing, chest tightness, or shortness of breath — reach out to your care team right away. Early action makes all the difference.

These practical tips are drawn from research and real patient experience. Always confirm with your oncologist or care team before making changes.

• At the first sign of loose stool, start your anti-diarrheal (like loperamide) — acting early helps prevent dehydration.
• Stay well hydrated, especially with electrolyte-rich fluids.
• Keep a log of frequency, severity, and possible food triggers.
• Ask your care team if “pre-emptive” loperamide (before expected diarrhea) is appropriate for you.

• Report any new/worsening cough, shortness of breath, or chest discomfort immediately.
• Expect regular lung monitoring— CT scans, pulse oximetry, or check-ins.
• If ILD is suspected, your doctor may pause treatment and start steroids.

Think of it like your car’s “check engine” light — it’s a signal to pause and get checked before something bigger develops.

Skin reactions are one of the most common side effects of HER2-targeted drugs like tucatinib and trastuzumab. They can show up early and, if unmanaged, may lead to treatment delays.

In trials like HERACLES and MOUNTAINEER, rash affected up to 35% of patients, with early onset being typical. Though often mild, it can escalate and interfere with quality of life or treatment adherence.

Skin reactions are not “cosmetic.” Studies show that unmanaged rash can lead to dose delays or discontinuation. On the flip side, early intervention is proven to keep more patients on therapy.

What helps:

• Ask for a baseline dermatology check before starting therapy.
• Use gentle, fragrance-free moisturizers and cleansers.
• Ask if your care team offers a “rash kit” (topical creams, soothing lotions).
• At the first sign of redness or itching, alert your team — don’t wait.
• Treatment may include topical steroids, antihistamines, or antibiotics like doxycycline.

Pro Tip: A 2022 study showed that patients who received early skin care support were more likely to complete their therapy successfully.

• Schedule rest breaks throughout your day — don’t wait until exhaustion hits.
• Incorporate light activity, like walking or stretching, can actually help energy levels.
• Good nutrition and hydration support recovery.
• If fatigue becomes overwhelming, ask your oncologist whether treatment adjustments or short breaks are possible.

When you’re juggling appointments, treatments, and life, it’s easy to forget the small details. But those small details can make a big difference.

Keeping a simple daily log helps your care team catch problems early — before they become serious.

Here’s what to track:

• What symptoms you notice (and when they happen)
• Which treatments or doses you received
• What helps or worsens your symptoms
• Missed doses or skipped activities

Studies across cancer types show that real-time symptom tracking can lead to earlier interventions, fewer hospitalizations, and even improved survival (because problems get caught before they escalate).

Asking clear questions helps you stay proactive and supported. Try:

1. Which side effects should I watch for most urgently with my prescribed regimen?
2. If I get diarrhea or shortness of breath, what’s step one?
3. How often will my lungs be checked (CT, oximetry, or other tests)?
4. Can I get referrals to skin, nutrition, or palliative care specialists?
5. If I need a treatment pause, what does that look like in practice?
6. Are there resources or support groups for people on HER2-targeted therapies?

Research in HER2+ colorectal cancer is moving fast — and these therapies are giving patients new options and new hope. But the key to success isn’t just the drug itself; it’s how well side effects are managed so treatment can continue safely and effectively.

By tracking your symptoms, speaking up early, and working closely with your care team, you can stay in the fight—and protect your quality of life.

At Fight CRC, we’re here for you — with resources, support, and community every step of the way. You don’t have to face this alone.