TL;DR
In the 551-patient HORIZON-Breast06 trial, trastuzumab rezetecan was associated with longer median progression-free survival than physician-selected chemotherapy for HER2-low metastatic breast cancer. Overall-survival data were immature, and the trial did not compare the drug with trastuzumab deruxtecan, an established treatment in some countries; serious treatment-related adverse events were more frequent with rezetecan.
A phase III trial in China found that trastuzumab rezetecan, an investigational antibody-drug conjugate, extended median progression-free survival compared with chemotherapy for people with HER2-low metastatic breast cancer. In the 551-patient HORIZON-Breast06 study, median progression-free survival was 16.4 months versus 6.8 months; the results were presented at the European Society for Medical Oncology congress in Madrid and published in JAMA on October 23, 2026.
Participants were randomly assigned to receive trastuzumab rezetecan or physician-selected chemotherapy: a taxane, eribulin, capecitabine or gemcitabine. The trial enrolled patients at 73 hospitals in China. Their median age was 55, about 73% had hormone receptor-positive disease, and 81.5% had not received chemotherapy for metastatic disease. The remaining participants had received one prior chemotherapy regimen for metastatic cancer.
The progression-free survival result was similar in the subgroup that had not previously received chemotherapy: 16.6 months with rezetecan and 6.8 months with chemotherapy (hazard ratio 0.25, 95% confidence interval 0.19-0.33). Among patients previously treated with chemotherapy, median progression-free survival was 13.9 versus 5.6 months (hazard ratio 0.32, 95% CI 0.19-0.54). These are trial comparisons against chemotherapy, not against another antibody-drug conjugate.
Investigators reported a progression-free survival advantage in both hormone receptor-positive and hormone receptor-negative groups. In the hormone receptor-positive group, medians were 16.4 and 6.7 months; in the hormone receptor-negative group, they were 16.5 and 6.8 months. The study team highlighted the latter finding because that subtype can be difficult to treat, but the subgroup results do not establish that every patient will benefit to the same degree.
A Longer Interval Before Progression
Progression-free survival measures the time patients live without their cancer worsening or death. The reported difference in median progression-free survival suggests that rezetecan could offer another treatment option for people with HER2-low metastatic disease if the findings support regulatory approval. It is relevant to both hormone receptor-positive and hormone receptor-negative disease, according to the trial results.
The result comes with a trade-off in reported toxicity. Grade 3 or higher treatment-related adverse events occurred in 84.1% of patients receiving rezetecan and 67.9% receiving chemotherapy. Serious treatment-related events were reported in 37.7% and 13.7%, respectively. Dose reductions were also more common with rezetecan, while discontinuations due to treatment-related events were 8.7% versus 6.3%. Seven rezetecan-treated patients, or 2.5%, developed interstitial lung disease; two cases were grade 3 and one was grade 4. These findings make both the potential benefit and the safety profile important to evaluation.
The study does not show that rezetecan is better than trastuzumab deruxtecan, a related drug already approved for several breast cancer settings in the United States. A larger progression-free survival benefit over chemotherapy cannot by itself establish superiority to that treatment, because there was no direct comparison.
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How Rezetecan Fits the Treatment Landscape
Trastuzumab rezetecan links an antibody that targets HER2 to a topoisomerase I inhibitor, a cell-killing drug. The source report says the medicine is already approved in China for advanced non-small cell lung cancer and colorectal cancer. In the United States, it has an orphan drug designation for gastric cancer; that designation is not an approval for breast cancer.
Trastuzumab deruxtecan, also known as T-DXd or Enhertu, is a similar antibody-drug conjugate with multiple U.S. breast cancer indications, including for HER2-positive, HER2-low and HER2-ultralow tumors. In an editorial accompanying the trial publication, Gustave Roussy researchers Maria Fernanda Mosele and Fabrice André said the HORIZON-Breast06 study did not establish that rezetecan is superior to T-DXd. They wrote that T-DXd is likely to remain the preferred option in countries where it is approved.
At ESMO, discussant Barbara Pistilli cited preclinical findings suggesting rezetecan may have greater membrane permeability and potency, and faster systemic clearance, than T-DXd. Those laboratory observations could point to differences in activity or toxicity, but they do not demonstrate a clinical advantage. Pistilli said trials should compare new antibody-drug conjugates with the current standard of care.
“Pivotal trials should generate evidence for regulatory approval by comparing new ADCs with the current standard of care.”
— Barbara Pistilli, ESMO discussant
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Survival and Comparative Benefit Remain Open
Overall-survival data were immature when the results were analyzed. The reported 12-month overall-survival rates were 90.6% with rezetecan and 81.4% with chemotherapy (hazard ratio 0.67, 95% CI 0.48-0.94; nominal P=0.01), and the investigators said the data favored rezetecan. These early figures do not yet establish a definitive overall-survival benefit; longer follow-up is needed.
The trial was conducted at hospitals in China and compared rezetecan with chemotherapy, rather than with T-DXd. The available report does not establish how results would compare in a head-to-head study or whether the treatment’s benefits and risks would be similar in other populations. It also does not establish a role for rezetecan in countries where it has not been approved for breast cancer.
Safety remains part of the unresolved picture. The higher rates of severe and serious treatment-related adverse events, along with the cases of interstitial lung disease, require consideration alongside the progression-free survival results. The trial findings do not determine which individual patients would be suitable for treatment.
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Follow-Up and Regulatory Review
The next evidence milestone is more mature overall-survival follow-up from HORIZON-Breast06, alongside continued monitoring of adverse events. Further reporting and review will be needed to clarify the durability of the survival findings and the treatment’s benefit-risk profile.
Regulatory decisions on rezetecan for breast cancer have not been established by this report. The source material does not specify an application timeline or a planned head-to-head trial against trastuzumab deruxtecan. Until comparative evidence or regulatory action is available, the drug’s place relative to approved breast cancer treatments remains unsettled.
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Key Questions
What did the HORIZON-Breast06 trial find?
The trial found longer median progression-free survival with trastuzumab rezetecan than with physician-selected chemotherapy: 16.4 months versus 6.8 months among all participants with HER2-low metastatic breast cancer. Overall-survival data were immature at the analysis.
Was rezetecan compared with Enhertu?
No. HORIZON-Breast06 compared rezetecan with chemotherapy, not trastuzumab deruxtecan (Enhertu). The results therefore do not establish that rezetecan is better than Enhertu.
What safety issues were reported?
Grade 3 or higher treatment-related adverse events occurred in 84.1% of patients on rezetecan and 67.9% on chemotherapy. Seven patients in the rezetecan group developed interstitial lung disease, including two grade 3 cases and one grade 4 case.
Is trastuzumab rezetecan approved for breast cancer?
The source report describes rezetecan as investigational for breast cancer. It says the drug is approved in China for advanced lung and colorectal cancers, but it does not report a breast cancer approval or a regulatory decision timeline.
Source: rss
