New FDA Approved Drug Combo Offers HER2-Positive Metastatic Breast Cancer Patients Hope

HER2-positive breast cancer gets its name because the cancer cells have too much of a protein called HER2, which stand for the human epidermal growth factor receptor 2. This type of cancer tends to grow faster, spread more easily, and come back more often. However, the good news is that it usually responds well to treatments that target the HER2 protein, like the antibody-drug conjugate Enhertu.

As per results from a clinical trial titled Phase 3 DESTINY-Breast09, this drug combination has been shown to reduce the risk of disease progression or death by 44% and extend the average progression-free survival to more than three years, compared to about two years with the former standard treatment.

Following the FDA approval of the drug combo, authorized on December 15, 2025, as a primary treatment option for patients with HER2-positive breast cancer that has spread and cannot be treated surgically, Dr. Francisco Esteva, an oncology specialist in New York, told SurvivorNet, “In my view, DESTINY-Breast05 is a trial that changes clinical practice.

“I will use ENHERTU in HER2 patients with residual disease after taxane [powerful chemotherapy drugs] and HP type of therapy [ cancers targeting HER2-positive cancers].

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The trial evaluated high-risk HER2-positive patients who still had invasive cancer following pre-surgery therapy, comparing Trastuzumab deruxtecan (T-DXd) to Trastuzumab emtansine (T-DM1). Those treated with T-DXd had a 9% higher rate of staying cancer-free compared to patients on T-DM1.

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Dr. Amy Comander, Director of Breast Oncology and Survivorship at Mass General Brigham Cancer Institute, also shared her enthusiasm about this new advancement.

“In this study, it was shown that the antibody-drug conjugate plus pertuzumab pushed median progression free survival to 40.7 months, far outpacing the 26.9 months achieved with a standard taxane, trastuzumab, and pertuzumab regimen,” Dr. Comander said.

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“The result signals a decisive shift away from chemotherapy-anchored care toward ADC-based strategies, ushering in a new era for patients with HER2-positive disease.

Meanwhile, Dr. Heather McArthur, Clinical Director of Breast Cancer and Komen Distinguished Chair in Clinical Breast Cancer Research at the University of Texas Southwestern (UTSW) Medical Center, considers the drug “practice-changing for certain patients.”

She characterized the approval as offering physicians a novel approach compared with current adjuvant therapies in a recent conversation with SurvivorNet.

“They have a lot of work ahead of them in terms of educating our colleagues around who actually is appropriate, how often to scan, and how to manage this differently than we’re used to in the adjuvant setting,” Dr. McArthur explained.

Dr. Kevin Punie, of University Hospitals Leuven, Gasthuisberg, Belgium, also spoke with SurvivorNet, noting how not all patients may need to continue this drug combination until their cancer progresses.

He explains that, for some individuals, a shorter initial treatment period of 12–18 weeks followed by maintenance therapy could provide similar benefits while reducing side effects and overall treatment burden, ultimately leading to improvements in quality of life.

In practice, he expects the approach to often include maintenance therapy, similar to the Phase III AFT-38 PATINA trial presented at the 2024 San Antonio Breast Cancer Symposiu, where patients with hormone receptor–positive breast cancer received a combination of endocrine therapy, trastuzumab, pertuzumab, and palbociclib as maintenance after their initial treatment.

Dr. Punie concluded, “I certainly think that we will more evolve into a little bit of a hybrid situation where the best elements of all clinical trials are being a little bit all put together and then patient per patient there will be some differences, but it’s good to have this option.

The doctor emphasizes how continuing this new therapy until disease progression may not be required for every patient with metastatic HER2-positive breast cancer.

However, like any treatment, this drug combination carries potential risks that patients should understand.

Enhertu warns it’s important to monitor for and promptly investigate signs and symptoms.

Boxed Warnings / Serious Risks

• Interstitial Lung Disease (ILD) / Pneumonitis
• Embryo-Fetal Toxicity – possibility of fetal harm if used during pregnancy
• Common Adverse Reactions
• Hematologic / Lab Abnormalities

Other signs and symptoms include:

• Decreased white blood cell count, neutrophil count, hemoglobin, lymphocyte count, or platelet count
• Nausea, vomiting, diarrhea, constipation, or decreased appetite
• Liver Enzyme/ Metabolic Changes
• Fatigue
• Alopecia (hair loss)
• Musculoskeletal pain
• Headache
• Respiratory infections

Dr. Esteva told SurvivorNet, “The serious ILD [interstitial lung disease], is less than one percent, but a nine percent improvement in disease-free survival in absolute numbers, not relative, is a significant improvement.

“So for women at very high risk who present with or have positive nodes after neoadjuvant therapy, this would be my go-to. But it is hard to give this full treatment. People get tired and so on, and only about 70% of patients actually made it to the full fourteen cycles.”

Dr. Kristina Fanucci, a breast medical oncologist in Boston, also acknowledges that the new combination offers significant benefits, but she still is wary about the potential side effects.

“I also have concerns about the increased side effects that come along with that regimen,” she told SurvivorNet.

How Does Trastuzumab Deruxtecan Work?

Trastuzumab deruxtecan is part of a class of cancer-fighting medications called antibody-drug conjugates (ADCs), antibody-based treatments that transport chemotherapy directly to cancer cells.

This therapy combines two approaches into a single treatment:

• Trastuzumab: An antibody specifically designed to find and bind to the HER2 protein on cancer cells
• Deruxtecan: A powerful chemotherapy drug attached to trastuzumab

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When administered into the bloodstream, the trastuzumab component of the drug specifically seeks out HER2-positive cancer cells, attaching to them like a key fitting into a lock. Once connected, it carries deruxtecan straight into the cancer cells, enhancing the chemotherapy’s potency while minimizing damage to healthy cells.

“Trastuzumab deruxtecan is an antibody-drug conjugate. What this means is it has two heads,” Dr. Isabel Preeshagul, a medical oncologist at Memorial Sloan Kettering Cancer Center in New York City, previously toldSurvivorNet.

“So, you have the part of the antibody that binds to the tumor cell, and then you have the other part that has the warhead or the chemotherapy agent. It’s almost like a Trojan horse. When I explain it to my patients, it’s like the horse looks very innocent and goes up to the tumor cell and binds to the tumor cell, and then unleashes this warhead and goes inside. And that’s how it kills the tumor.”

Trastuzumab is precise and powerful and aims specifically at cancer cells, thereby enhancing effectiveness and decreasing overall side effects.

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Questions To Ask Your Doctor

• Am I a candidate for T-DXd (Enhertu) plus pertuzumab?
• How will we check for lung side effects, and how often?
• If my tumor shrinks, can we pause treatment or lower the dose?
• Will my insurance cover a newer drug?
• Could I still join a clinical trial later if the cancer grows?

Contributing: SurvivorNet Staff

Learn more about SurvivorNet's rigorous medical review process.

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