Hengrui's Breast Cancer Drug More Than Doubled Progression-Free Survival While Severe Anemia Hit Four in Ten Patients

Ying Fan was given ten minutes on the Madrid schedule, 13:40 to 13:50 on October 23 in the Alicante Auditorium. Her phase 3 trial was one of 64 research findings Hengrui Pharma brought to the European Society for Medical Oncology congress. Two of its numbers belong in the same sentence. Patients on Hengrui’s antibody-drug conjugate, trastuzumab rezetecan, went a median 16.4 months before their breast cancer progressed, against 6.8 months on chemotherapy, and 42.8 percent of them developed grade 3 or worse anemia, against 4.8 percent of the chemotherapy patients.

Fan, an oncologist at the Cancer Hospital of the Chinese Academy of Medical Sciences, presented the trial, HORIZON-Breast06, as late-breaking abstract LBA13, and the results appeared the same day in JAMA. The trial’s principal investigator, Binghe Xu, works at the same hospital. MedPage Today ran the result under the headline “Chinese Drug Shows Benefit in HER2-Low Breast Cancer,” and on the efficacy side the headline is accurate. The rest of the results tables, which cover blood counts, the comparator the trial left out, and where its patients came from, deserve the same billing.

HER2-low is a recent label. It covers tumors that show a faint signal of the HER2 protein, scored 1+ or 2+ on immunohistochemistry without gene amplification. Oncology filed those tumors as HER2-negative until AstraZeneca and Daiichi Sankyo’s trastuzumab deruxtecan, sold as Enhertu, showed that an antibody-drug conjugate could latch onto even that faint signal and release a chemotherapy toxin inside the cell. Hengrui’s drug uses the same design, with a topoisomerase I inhibitor as its payload, at about six drug molecules per antibody and a dose of 6.4 mg/kg every three weeks.

According to OncoDaily’s detailed account of the presentation, the trial randomized 551 patients one to one at 73 hospitals in China, either to the drug or to a chemotherapy of the physician’s choice. Of those patients, 81.5 percent had never had chemotherapy for metastatic disease, about 73 percent had hormone-receptor-positive tumors, more than three-quarters had cancer in their organs, and about 54 percent had liver involvement. The trial was open-label, so everyone knew who got what, but its primary endpoint, progression-free survival, was judged by blinded independent central review.

On that endpoint the result was not close. Median progression-free survival was 16.4 months on trastuzumab rezetecan and 6.8 months on chemotherapy, a hazard ratio of 0.27 (95 percent confidence interval 0.21 to 0.34). The chemotherapy-naive patients came out at 16.6 months against 6.8. At one year, 63.1 percent of patients on the drug had not progressed, compared with 18.0 percent on chemotherapy. Tumors shrank measurably in 75.5 percent against 41.2 percent, and those responses lasted a median 15.0 months against 6.8. The advantage held in hormone-receptor-positive and hormone-receptor-negative disease, and in the minority who had already had a line of chemotherapy, where the medians were 13.9 months against 5.6.

Nine times the severe anemia

Grade 3 or worse treatment-related adverse events struck 84.1 percent of patients on the drug and 67.9 percent on chemotherapy. Chemotherapy is hard on white cells, and that was the one measure where the arms stayed close, with grade 3 or worse drops in neutrophil count in 65.2 percent against 54.2 percent. The arms separated on red cells and platelets. Grade 3 or worse anemia hit 42.8 percent of the drug arm and 4.8 percent of the chemotherapy arm. Grade 3 or worse thrombocytopenia, a loss of the platelets that let blood clot, hit 35.9 percent against 1.8 percent. Febrile neutropenia, the feverish collapse of white cells that often ends in a hospital admission, occurred in 9.8 percent against 0.4 percent. About half the patients on the conjugate had their dose cut.

The drug held the cancer back. It did not hold back the bone marrow.

Lung injury, the toxicity that has followed this drug class, looked comparatively quiet. Seven patients on rezetecan, 2.5 percent, developed interstitial lung disease, including two grade 3 cases, one grade 4 case, and no deaths. A subgroup analysis of 213 Asian patients in Enhertu’s DESTINY-Breast04 trial found adjudicated drug-related lung disease in 14.3 percent of those given trastuzumab deruxtecan, mostly grade 1 or 2. That comparison flatters Hengrui’s drug, but the two trials enrolled different patients and adjudicated and followed them differently, and HORIZON-Breast06 excluded anyone with a history of interstitial lung disease. In Hengrui’s trial the median time to onset of lung injury was about 316 days, so the problem took close to a year to appear, and longer follow-up has room to find more of it.

Overall survival is not mature. At the March 20, 2026 data cutoff, 66 of 277 patients on the drug had died, against 77 of 274 on chemotherapy, for an exploratory hazard ratio of 0.67, with a 95 percent confidence interval of 0.48 to 0.94. At twelve months, 90.6 percent were alive on the drug and 81.4 percent on chemotherapy. That is an early signal pointing the right way, drawn from an exploratory analysis taken while three-quarters of patients were still alive. It is not yet a demonstrated survival benefit.

The opponent that wasn’t in the ring

HORIZON-Breast06 beat chemotherapy. It never faced trastuzumab deruxtecan, the drug any oncologist reading the data will want it measured against, and it excluded patients who had already received HER2-directed therapy or a prior antibody-drug conjugate with a related payload. It therefore says nothing about how the drug performs after Enhertu or against it. A cross-trial comparison is tempting, since in DESTINY-Breast06, Enhertu’s trial in chemotherapy-naive HER2-low disease, median progression-free survival was 13.2 months against 8.1. But the populations, comparators, and countries differ, and no patient in either trial was randomized between the two conjugates. Superiority over Enhertu remains unknown.

Hengrui has registered the trial that would answer it. A randomized phase 2 study is set up to compare doses of trastuzumab rezetecan with trastuzumab deruxtecan in 150 patients with hormone-receptor-positive, HER2-low disease, with progression-free survival as its primary endpoint, and it has posted no results. Sichuan Baili Pharmaceutical has registered a similar 120-patient comparison for its own conjugate. Meanwhile, at the same Madrid meeting, Chia Tai Tianqing’s TQB2102 reported APEX-Breast01, another China-only phase 3 against chemotherapy, with the same 16.4-month median against 5.5 months and a Chinese marketing application already accepted for review. Chinese companies keep clearing the chemotherapy bar, and none has yet shown its drug beats Enhertu.

Roughly 97 percent of HORIZON-Breast06’s participants were Han Chinese, and every one was treated in China. In February 2022, the FDA’s Oncologic Drugs Advisory Committee voted 14 to 1 that Eli Lilly and Innovent’s PD-1 drug sintilimab, backed by a China-only phase 3, needed “additional clinical trial(s) demonstrating applicability to U.S. patients and U.S. medical care” before a final decision. Richard Pazdur, who runs the agency’s Oncology Center of Excellence, said that “single-country submissions is a step backward.” Six weeks later the FDA rejected the application and recommended a multiregional trial, citing the trial’s endpoint and control arm as well as its single-country design. That case involved a different drug and a different disease, and it does not decide how regulators would treat HORIZON-Breast06. It does mean that a toxicity profile this heavy, recorded in a single population under a single country’s supportive-care practices, is unproven everywhere else, and the trial has no data that could show otherwise.

Hengrui has kept those markets out of reach for now. When it licensed trastuzumab rezetecan to India’s Glenmark in September 2025, for more than $18 million upfront and up to $1.093 billion in milestones, the deal excluded the United States, Canada, Europe, and Japan along with China itself. The company describes the drug as in development for more than ten indications.

Hengrui came to Madrid with the better progression curve, and the same tables showed its patients nearly nine times as likely to become severely anemic. The trial that could tell an American oncologist whether any of that beats the Enhertu already stocked in U.S. infusion centers exists only as a registration on ClinicalTrials.gov, with no results.

Sources

1. OncoDaily: HORIZON-Breast06 at ESMO 2026
2. JAMA: HORIZON-Breast06, trastuzumab rezetecan vs chemotherapy in HER2-low advanced breast cancer (2026)
3. MedPage Today: Chinese Drug Shows Benefit in HER2-Low Breast Cancer
4. Hengrui Pharma: ESMO Congress 2026 preview of 64 research findings
5. Breast Cancer (Tokyo): DESTINY-Breast04 Asian subgroup analysis (2024)
6. ClinicalTrials.gov: NCT07497386, trastuzumab rezetecan vs trastuzumab deruxtecan
7. ClinicalTrials.gov: NCT07678957, BL-M07D1 vs DS-8201
8. OncoDaily: APEX-Breast01 at ESMO 2026
9. The Cancer Letter: ODAC votes 14 to 1 on China-only sintilimab data (2022)
10. Healio: FDA rejects sintilimab with chemotherapy for non-small cell lung cancer (2022)
11. PharmExec: Glenmark’s licensing deal for Hengrui’s trastuzumab rezetecan (2025)