Anbenitamab + HB1801 in HER2-Positive Metastatic Breast Cancer: HEALER Results Published in the NEJM

A HER2 Antibody That Binds Two Sites, Compared With Standard Therapy in Metastatic Breast Cancer: HEALER Results in NEJM

For about 15 years, THP (trastuzumab + pertuzumab + docetaxel) has been the first-line standard for HER2-positive metastatic breast cancer. In a large phase 3 trial conducted in China, it was compared with a new regimen. The results of the HEALER trial, which combined anbenitamab, a bispecific antibody that binds HER2 at two separate sites, with HB1801, an albumin-bound form of docetaxel, were presented at ESMO 2026 and published on 24 October 2026 in the New England Journal of Medicine. The new regimen cut the risk of disease progression roughly in half; however, serious side effects were also more common. We covered the Neo-HEALER trial, which compared the same drug pair with THP before surgery, in an earlier article. We have also written separately about the first-line approval of trastuzumab deruxtecan + pertuzumab, progress in metastatic HER2-positive breast cancer and the highlights of ESMO 2026.

Why does this matter?

About 15–20% of breast cancers are HER2-positive; in these tumors the HER2 protein is present in excessive amounts on the cell surface, and the disease tends to progress faster (breast cancer symptoms and stages). Although metastatic HER2-positive breast cancer cannot be cured permanently today, treatments that target HER2 can keep it under control for years. Since 2012, the first-line standard has been the THP regimen, based on the CLEOPATRA trial; however, with this treatment the disease progresses again within two years in about half of patients.

In recent years, trials challenging this standard have increased. The most important was DESTINY-Breast09, which compared trastuzumab deruxtecan (T-DXd) + pertuzumab with THP, and this regimen was approved for first-line use in the United States (the T-DXd + pertuzumab regimen). However, as the authors of the paper also emphasize, access to new drugs, cost and side effect profiles show that effective additional options are still needed in many parts of the world. HEALER is a response to this need from China.

What is anbenitamab + HB1801, and what did the HEALER trial show?

Anbenitamab is a bispecific antibody that binds the HER2 protein at two different sites; HB1801 is an albumin-bound form of docetaxel. In the HEALER trial, this pair was compared with standard THP as first-line treatment for HER2-positive metastatic breast cancer and raised the proportion of patients alive without progression at 24 months from 34.4% to 58.5%; serious side effects, meanwhile, rose from 34.4% to 45.9%.

Two new drugs: anbenitamab and HB1801

Anbenitamab (KN026) is a bispecific antibody designed to do the work of the two separate antibodies in THP (trastuzumab and pertuzumab) in a single molecule (bispecific antibodies). Laboratory studies have shown that it binds HER2 more strongly than trastuzumab or pertuzumab and further increases the uptake of HER2 into the cell and its breakdown. In May 2026 it was approved in China for previously treated HER2-positive advanced gastric cancer (gastric cancer).

HB1801 is a form of docetaxel bound to albumin nanoparticles. Albumin is used instead of the solvent used in classic docetaxel; in the trial, HB1801 was given at a dose of 100 mg/m², and docetaxel in the THP arm at 75 mg/m². HB1801 is not approved for breast cancer.

How was the trial conducted?

The median age of the patients was 54–55, and all were women. About 55% had hormone receptor-positive tumors, and 71% had visceral metastases (such as in the liver or lungs); about 56% had metastatic disease at first diagnosis. Only 18–21% had previously received trastuzumab for early-stage disease, and about 7% had received pertuzumab. Only 2 patients had brain metastases. An important detail: patients with hormone receptor-positive disease did not receive hormone therapy or a CDK4/6 inhibitor during the trial.

Results: disease control

At the interim analysis in April 2026 (median follow-up 21 months), disease progression or loss of life had occurred in 149 patients (33.5%) in the new regimen arm and in 252 patients (57.3%) in the THP arm. This difference crossed the prespecified early efficacy boundary.

The benefit was similar in all prespecified subgroups: regardless of age, hormone receptor status, visceral or liver metastases, prior trastuzumab use and HER2 level, the hazard ratio stayed between 0.38 and 0.59. The investigators' own assessment gave a similar result (HR 0.52).

An HR below 1 favors the new regimen. Subgroup analyses are exploratory; confidence intervals are wide, especially in small groups (for example, 0.25–0.88 in those aged 65 or older).

Side effects

With the new regimen, patients received the antibody for a median of 16.6 months and HB1801 for a median of 4.8 months; in the THP arm these durations were 13.8 and 5.5 months. Although the new regimen was used for longer, the rate of stopping treatment because of side effects remained low; however, serious side effects and dose reductions were clearly more common.

• Blood counts: The most common serious side effects were low neutrophil counts (13.1% versus 8.4%) and low white blood cell counts (9.7% versus 5.5%). Signs of infection such as fever or chills call for contacting a doctor right away (leukopenia and neutropenia, which symptoms warrant a call).
• Diarrhea: A common side effect of HER2 treatments; it occurred in 53.2% of patients on the new regimen, but severe diarrhea occurred in only 2.3%, and no one stopped treatment because of it (the antidiarrheal drug loperamide).
• Edema and low albumin: Leg edema (28.8% versus 14.6%) and low blood albumin (37.6% versus 22.8%) were about twice as common with the new regimen (edema in people with cancer).
• Heart: HER2 treatments can affect the heart's pumping strength. With the new regimen, impaired heart function occurred in 2.9% of patients and a drop in ejection fraction in 8.1%; severe cases were 0.5% and 1.8%. One patient had sudden cardiac arrest due to a heart attack 3 days after the fifth cycle, resulting in loss of life; the investigators do not attribute this to a direct effect of the drug, but state that longer follow-up is needed for cardiac safety.
• Lungs: Interstitial lung disease, which is closely watched with HER2 treatments, occurred in 4 patients (0.9%) on the new regimen; it was severe in one.
• Loss of life: Loss of life related to side effects occurred in 2 patients (0.5%) in each arm: sudden cardiac arrest and cardiopulmonary arrest with the new regimen, and pneumonia and pulmonary embolism in the THP arm.

Which drug does the benefit come from?

The most important design problem in HEALER is that two drugs were changed at once in the comparison: both the HER2 antibody (anbenitamab instead of trastuzumab + pertuzumab) and the chemotherapy drug (higher-dose HB1801 instead of docetaxel) differ. As a result, it is not possible to know how much of the difference in outcome comes from the antibody and how much from the chemotherapy.

This distinction matters in practice: if a large part of the benefit comes from the higher dose of the chemotherapy drug, the increase in anemia, edema and neutropenia is most likely linked to it as well. Chemotherapy was given for a median of 4.8 months with the new regimen; after that, patients continued with the antibody alone. For this reason, what will determine quality of life in the long term is the side effect profile of the antibody on its own (long-term side effects of chemotherapy).

How does it compare with other trials?

Median progression-free survival in the HEALER THP arm (14.3 months) is similar to that in the PUFFIN trial in China and in real-world data (13.6–15.0 months), but shorter than in the control arms of CLEOPATRA (18.7 months) and especially DESTINY-Breast09 (26.9 months). The authors attribute this difference to differences in trial design, patient populations and the proportion of patients censored from follow-up. The worse the control arm does, the larger the advantage of the new treatment may appear; this detail should therefore be kept in mind when interpreting the relative benefit (reading research correctly).

T-DXd + pertuzumab and anbenitamab + HB1801 have not been compared directly. The hazard ratios of the two trials (about 0.56 in DESTINY-Breast09 and 0.46 in HEALER) should not be placed side by side: patient populations, the course of the control arms and follow-up times differ. The fact that patients with hormone receptor-positive disease in HEALER did not receive maintenance hormone therapy also differs from current practice (options in hormone receptor-positive breast cancer).

Limitations

• Interim analysis: It was performed at about 70% of the planned events; overall survival data are not yet mature. The company's June 2026 announcement mentioned a favorable trend in overall survival; the NEJM paper, however, reports no results on this.
• A single country: All patients were from China; the results need to be confirmed in other populations.
• Control arm: THP was chosen because T-DXd + pertuzumab was not approved when the trial began; today the standard has changed in some countries.
• Open-label design: Patients and physicians knew the treatment; however, assessment of the primary endpoint by a blinded independent central review reduces this problem.
• Two drugs changed at once: The contributions of the antibody and the chemotherapy cannot be separated.
• Selected patient population: Few patients had received trastuzumab for early-stage disease (19%), and patients with brain metastases were almost absent (brain metastases in breast cancer). This limits how far the results can be generalized to countries where most patients have received intensive HER2 treatment at an early stage.
• Funding: The trial was supported by the company that owns both drugs (Shanghai JMT-Bio; CSPC group); some of the authors are company employees.

Tips for patients and their families

• Today's standard has not changed: In Turkey, THP is an effective and proven treatment for HER2-positive metastatic breast cancer. HEALER shows that options may increase in the future; however, there is no access to this regimen for now.
• Discuss the choice of treatment: Hormone receptor status, prior HER2 treatments, brain metastases and expected side effects influence the choice of first-line treatment. Make your decision together with your doctor; if needed, get a second opinion.
• Report side effects early: Diarrhea, edema, shortness of breath, cough and fever are symptoms to watch for with HER2 treatments. Nutrition and fluid intake can help ease side effects (easing side effects through nutrition).
• Heart monitoring: While receiving HER2 treatment, it is important to have a heart ultrasound (echocardiography) at regular intervals.

Frequently asked questions

What is anbenitamab?

Anbenitamab (KN026) is a bispecific antibody that binds the HER2 protein at two different sites. It was designed to do the work of trastuzumab and pertuzumab in THP in a single molecule. It was approved in China for HER2-positive gastric cancer in May 2026; it is not yet approved for breast cancer.

What did the HEALER trial show?

In 885 patients with HER2-positive breast cancer who had not yet received treatment for advanced disease, anbenitamab + HB1801 reduced the risk of disease progression by 54% compared with THP. At 24 months, 58.5% versus 34.4% of patients were alive without progression, and tumors shrank in 87.6% versus 73.4%.

Does it cause more side effects than THP?

Yes. Grade 3 or higher side effects occurred in 45.9% versus 34.4%. Anemia, diarrhea, hair loss, edema and low neutrophil counts were more common; however, the rate of stopping treatment remained low (5.2% versus 3.4%). Loss of life related to side effects occurred in 2 patients in each arm.

Can this treatment be used in Turkey?

No. As of October 2026, anbenitamab and HB1801 are not licensed in Turkey. Anbenitamab is approved only in China, for gastric cancer. In Turkey, THP is used as the standard first-line treatment.

Glossary

HER2

A protein that is present in excessive amounts on the cell surface in some breast cancers and stimulates cell growth.

Bispecific antibody

An antibody that can bind two different targets, or two different sites on the same target, with a single molecule.

THP

The combination of trastuzumab, pertuzumab and docetaxel; the standard first-line treatment for HER2-positive metastatic breast cancer.

Albumin-bound docetaxel

A form of the chemotherapy drug docetaxel prepared by binding it to albumin, a protein in the blood.

Progression-free survival

The time after the start of treatment during which the disease does not progress.

Hazard ratio (HR)

The ratio of the rates at which events occur in two treatment groups; a value below 1 favors the new treatment.

Interim analysis

An assessment performed at a prespecified point before the trial is completed.

Open-label trial

A trial in which patients and physicians know which treatment is being given.