Targeting HER2 in colorectal cancer: New survival data emerges

For people living with HER2-positive metastatic colorectal cancer (CRC), treatment options can feel limited, especially when standard chemotherapy stops working. But new research presented at the 2026 American Association for Cancer Research (AACR) Annual Meeting offers encouraging news: a targeted therapy called trastuzumab deruxtecan (Enhertu) may help patients live longer than standard chemotherapy, particularly when used earlier in treatment.

The findings suggest that this newer therapy could become an important option for improving outcomes in this aggressive form of CRC.

What is HER2-positive metastatic CRC?

HER2-positive metastatic CRC is when CRC tumor cells make too much of a protein called HER2. This protein can fuel cancer growth and make the disease harder to treat.

Patients often have fewer effective treatment options after standard chemotherapy because this subtype can be aggressive. That’s why researchers are exploring targeted therapies to attack specific features of cancer cells while limiting damage to healthy cells.

How does trastuzumab deruxtecan work?

Trastuzumab deruxtecan (T-DXd) is a type of treatment called an antibody-drug conjugate (ADC).

This therapy combines:

• An antibody that seeks out HER2-positive cancer cells
• A chemotherapy drug attached to that antibody

This allows the treatment to deliver chemotherapy directly to cancer cells, helping spare more healthy tissue compared with standard chemotherapy.

This “guided delivery” approach has already shown success in other HER2-positive cancers, including breast cancer, and researchers are now seeing similar promise in CRC.

What did the new study find?

Researchers at Roswell Park Comprehensive Cancer Center reviewed real-world outcomes from 11,112 patients with HER2-positive metastatic CRC:

• 9,135 patients received standard chemotherapy
• 1,977 patients received trastuzumab deruxtecan

At the one-year mark, overall survival was similar between the two groups. Over time, a clear difference emerged.

After five years, the survival rate was:

• 58% for patients treated with trastuzumab deruxtecan
• 49% for patients treated with standard chemotherapy

That means patients who received trastuzumab deruxtecan had a better chance of long-term survival.

Why timing may matter

Trastuzumab deruxtecan has typically been given later in treatment, often after two or more prior therapies.This study suggests that using the drug earlier may lead to better long-term outcomes.

This idea mirrors what researchers have already seen in HER2-positive breast cancer, where antibody-drug conjugates have shown greater benefit when used sooner.

What this means for patients

These findings are encouraging because they show that the benefits seen in clinical trials may also translate into real-world patient care.

That means trastuzumab deruxtecan may offer patients:

• Longer overall survival
• A lower risk of death
• A targeted alternative to standard chemotherapy
• Potentially better outcomes when used earlier

For patients with HER2-positive metastatic CRC, this could represent an important step toward more personalized treatment options.

What are the next steps?

While these results are promising, researchers caution that more studies are needed before treatment guidelines change.

Since this was a retrospective real-world study, the next step will be prospective clinical trials to confirm whether trastuzumab deruxtecan should be moved earlier in the treatment sequence.

Researchers are also continuing to monitor side effects, including pulmonary toxicity, a lung-related side effect that can occur with this therapy.

Still, experts say these findings highlight the growing role of precision medicine in CRC care. 

If you or a loved one has HER2-positive metastatic CRC, ask your care team whether HER2 testing and targeted therapy options may be appropriate as part of your treatment plan.

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