First FDA-approved Treatment for HER2-positive Metastatic Colorectal Cancer 


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The Food and Drug Administration (FDA) has granted accelerated approval for a combination therapy for patients who qualify, with one criteria being HER2-positive metastatic colorectal cancer. HER2-positive is a biomarker initially discovered in breast cancer but also present in about 3% to 5% of colorectal cancer cases.

Medical information

The FDA grants accelerated approval “to allow for earlier approval of drugs that treat serious conditions, and fill an unmet medical need.” On January 19, 2023, the combination of two targeted drugs, tucatinib (Tukysa®) and trastuzumab (Herceptin®), received this designation.

Tukysa is a pill and a targeted drug for HER2. Herceptin, a drug that’s been used for treating breast and stomach cancers for many years, is administered through IV. A significant advantage of this combination is that neither of the two drugs are chemotherapy; rather, they are targeted therapies. One benefit of targeted therapies is that they deliver toxins that kill cancer cells without harming healthy cells.

Who is the treatment for?

This new combination treatment is only available for patients who meet all of these criteria:

  • RAS Wild-type
  • HER2-positive metastatic colorectal cancer
  • Have advanced colorectal cancer that cannot be removed surgically or where it has metastasized to other parts of the body
  • Have already received some form of chemotherapy that contained 5-FU or capecitabine, irinotecan, and oxaliplatin

The Tukysa and Herceptin combination is the first FDA-approved treatment for HER2-positive metastatic colorectal cancer.  

Is the treatment safe and effective?

Yes, the treatment was studied as part of the MOUNTAINEER study, and it was conducted safely under the highly regulated clinical trials process.

The study shows promise for patients who qualify. Scientists who led this effort provided evidence from phase 2 of the MOUNTAINEER clinical trial to the FDA, which resulted in fast tracking this treatment combination. 

The MOUNTAINEER phase 2 clinical trial research focused on people with HER2-positive biomarkers with metastatic colorectal cancer and who have already received chemotherapy.  

The results from the MOUNTAINEER study found that:

  • The average amount of time a patient’s condition improved was about 12.4 months, with a range between 8.5 months and 20.5 months. 
  • The average length of time the disease did not progress was approximately 8.2 months, with a range of 4.2 months to 10.3 months. 
  • The average overall survival time was about 24.1 months, with a range of 20.3 months to 36.7 months. 

When the patients entered the study, about 64.3% of them had cancer that had spread to the liver, and about 70.2% had cancer that had spread to the lungs. Prior to the study, these patients had received an average of three rounds of treatment, with a range of one round to six rounds. 

Patient assistance for the clinical trial was provided by Seagan for both insured and uninsured patients. This trial showed a significant number of people see dramatic reductions of their tumor’s size and also that the duration of this treatment’s effects lasted longer than standard of care treatment.

Ask the expert

Suneel D. Kamath, MD, gastrointestinal oncologist, Cleveland Clinic

Q. In your opinion, does this provide a durable, long-lasting response for stage IV colorectal cancer? How exciting is this on a scale of 1-10? 

A. It is durable, which means the effect of treatment is long-lasting. The median duration of the responses seen is over one year, which is good. It’s much better than most chemotherapy trials and many other treatments that we use. Response lasting for over a year is impressive for people with cancers that have become resistant to multiple prior treatments. Also, that survival being on average over two years is also very impressive. 

Suneel Kamath, MD, gastrointestinal oncologist, Cleveland Clinic

On a scale of 1 to 10, the Tukysa and Herceptin combination rates as an 8. 

The only reason the rating is not higher is due to the rarity of mutation.  

Overall, the Tukysa and Herceptin combination will only benefit 3% to 5% of people with metastatic colorectal cancer. It is difficult to be extremely enthusiastic about a treatment that only benefits a few people. 

However, the quality of the data and how well people did with the Tukysa and Herceptin combination – both in terms of how long people were able to live and also with side effects being mild – is very encouraging. It’s also heartening to see advancements to treatments for colorectal cancer arising out of clinical trials. 

Some patients who began this study back in 2017 continued on with Tukysa and Herceptin treatment and have not had tumor growth. Although it’s uncommon, and a small group of patients, it’s incredible how much more life these patients have been able to live. They’ve seen and attended family events and milestones, such as graduations, anniversaries, birthdays, births. 

The ability to see patients live past five years with metastatic colorectal cancer is both inspiring and invigorating.  

Research is advancing, and that is a reason to hope.

Patient pro tip

Ashley Pedro, stage IV survivor

"I'm not HER2-positive, but I know my biomarkers. On my last trip to MD Anderson, I learned that several of my tumors grew. In mid-June I will be screened for a study that would not have been an option if I did not know my biomarkers. Wish me luck! The current standard of care is not currently working as well as it should, and I am hoping this clinical trial will either stabilize or get rid of my tumors and open the doors to help other patients with the same mutation I have."
–Ashley Pedro, stage IV survivor

“Although I’m not a patient eligible for HER2 treatment, for the one in seven rectal cancer patients who have HER2 mutation, this treatment option gives hope of longer quality time on treatment. As this moves into earlier treatment lines, knowing one's biomarkers becomes more important than ever”

–Annie Delores, Fight CRC Research Advocacy Training and Support member

Practically speaking: Do you qualify for the treatment?

First, it’s important to know your biomarkers. This treatment combination is only offered to patients with RAS Wild-type HER2-positive metastatic colorectal cancer. 

Next, if you think you may qualify for this combination treatment, talk to your oncologist. A few questions to ask:

  • I read about the FDA’s recent approval of Tukysa and Herceptin, and I believe I could qualify. Do you agree?
  • Do you feel like I would benefit from being on this targeted therapy? Why or why not?
  • Would this cancer center be able to administer the treatment to me if I’m a candidate?
  • From your understanding of the trial and the therapy, what are some of the big side effects I should watch out for? 
  • If I qualify, what are my next steps?

Your Guide in the Fight

We are fighting alongside you from your day of diagnosis and beyond. You can find additional resources in our Resource Library, or here are a few quick links to help you apply this information:

To talk with someone about this information and/or ask questions, join us at our next Resource Meetup or our Community of Champions now.

Medical input and review

Suneel D. Kamath, MD, gastrointestinal oncologist, Cleveland Clinic

Medical disclaimer

The information and services provided by Fight Colorectal Cancer are for general information purposes only. The information and services are not intended to be substitutes for professional medical advice, diagnoses or treatment. If you are ill, or suspect that you are ill, see a doctor immediately. In the event of an emergency, call 911 or go to the nearest emergency room. Fight Colorectal Cancer never recommends or endorses any specific physicians, products, or treatments for any condition.

Funding disclosure

Fight Colorectal Cancer has received funding from Seagan, the producers of Tukysa, and Genentech, the producers of Herceptin, in the form of unrestricted educational grants. We maintain ultimate authority over website content and the content written in this article.

2 thoughts on “First FDA-approved Treatment for HER2-positive Metastatic Colorectal Cancer 

  1. My husband has HER2 and KRAS 12GD ? Mutation would these drugs be useful or is there any other drugs suitable he is starting to progress on Folfuri and Avastin thanks Cathy

    1. Hi Cathy: The combination of drugs mentioned in the blog, tucatinib and trastuzumab, are typically used for HER2-positive cancers. However, in this particular case, the presence of the KRAS mutation (KRAS G12D) means that these drugs may not be suitable. As mentioned in the blog, one of the criteria for treatment is being RAS wild type, and being KRAS mutant indicates that this is not the case. The combination of HER2-positive and KRAS-positive mutations is uncommon. As they often don’t occur together. It would be advisable to seek guidance from a knowledgeable colorectal cancer oncologist, preferably at an NCI-designated cancer center.

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