Trastuzumab Rezetecan's HER2-Low Breast Cancer Win: 16 Months Without Progression, 84% Severe Side Effects

A new drug has just posted one of the strongest results ever seen in HER2-low advanced breast cancer — and the hardest question about it has nothing to do with whether it works. In the phase 3 HORIZON-Breast06 trial, published in JAMA on 23 October and presented at the ESMO 2026 congress in Madrid, trastuzumab rezetecan kept cancer from growing for a median of 16.4 months, against 6.8 months on physician's choice of chemotherapy. Tumours shrank in 75.5% of patients on the drug, against 41.2% on chemotherapy. The risk of progression or death fell by 73%.

HER2-low is a category that barely existed a few years ago. These are tumours with low levels of the HER2 protein — too little to qualify as HER2-positive, which is what the classic targeted drugs were built for. Roughly half of all breast cancers fall into this group, and until recently their patients simply got chemotherapy, because no targeted therapy was designed for them. That changed when antibody-drug conjugates — a homing antibody carrying a chemotherapy payload straight into the cancer cell — proved they could work at low HER2 levels. Trastuzumab rezetecan, developed by China's Hengrui Pharma under the code SHR-A1811 and sold in China as Aiweida, is the newest member of that class to clear a phase 3 trial.

The trial itself was straightforward and hard to argue with: 551 women with HER2-low unresectable or metastatic breast cancer, randomised one-to-one across 73 hospitals in China, the drug against whatever chemotherapy their doctor would otherwise have chosen. It met both of its primary endpoints. Among patients who had never had chemotherapy for metastatic disease, the gap was nearly identical — 16.6 months against 6.8. At twelve months, 65.2% of patients on the drug were still free of progression, against 18.9% on chemotherapy. Responses lasted a median of 15 months, against 6.8.

But the numbers that will decide this drug's fate are the ones underneath the headline. Severe treatment-related side effects — grade 3 or higher — struck 84.1% of patients on trastuzumab rezetecan, against 67.9% on chemotherapy, and more than half of the patients on the drug needed at least one dose reduction to cope. Interstitial lung disease, the feared complication of this whole drug class, appeared in 2.5% of patients. And the survival data are not yet mature: at the data cutoff, 23.8% of patients on the drug had died against 28.1% on chemotherapy, with an estimated twelve-month survival of 90.6% against 81.4% — encouraging, but a descriptive analysis, not a verdict.

There is also a comparison nobody should make, and everybody will. The incumbent drug in this space, trastuzumab deruxtecan — Enhertu — posted 13.2 months against 8.1 on chemotherapy in its own phase 3 trial, a hazard ratio of 0.62. On paper, the new drug looks far better. But the two drugs have never been tested head to head, and Enhertu's trial ran against a stronger control arm: its chemotherapy patients lasted 8.1 months without progression, against 6.8 here. A weaker control arm inflates the apparent advantage, so the honest reading is that both drugs work well, and nobody knows which works better. At the same ESMO meeting, a second Chinese antibody-drug conjugate, TQB2102, posted near-identical numbers — 16.4 months against 5.5, a hazard ratio of 0.29 — which suggests the 16-month figure may say as much about the trial populations as about either drug.

What happens next is a regulatory question, and the pieces are already moving. Trastuzumab rezetecan is approved in China for HER2-mutant lung cancer and HER2-positive colorectal cancer, and Hengrui had a breast cancer indication accepted by China's National Medical Products Administration in September 2025 under priority review. In September of that year it also licensed the drug's rights outside China to Glenmark — but pointedly kept the United States, Canada, Europe and Japan for itself, which is not what a company does when it plans to stay a domestic player. My judgement is that China's regulator approves the HER2-low indication by the end of 2027, but it is a closer call than the efficacy numbers suggest: the survival data are immature, the toxicity bill is heavy, and Enhertu already serves this exact population in China, so the regulator can afford to ask for more. The bigger story is what two Chinese antibody-drug conjugates posting 16.4-month results in the same week means for the field. The HER2-low space is about to get crowded, and crowded is when prices fall, access widens, and the question stops being whether these drugs work and starts being who gets them.