In the phase III HEALER trial, first-line treatment with the HER2-targeted bispecific antibody anbenitamab plus albumin-bound docetaxel (HB1801) significantly improved progression-free survival compared with docetaxel, trastuzumab, and pertuzumab (THP) in patients with HER2-positive advanced breast cancer. The findings were reported at the European Society for Medical Oncology (ESMO) Congress 2026 (Abstract LBA15), as well as published in The New England Journal of Medicine by Wang et al.
At a median follow-up of 21 months, the estimated 24-month progression-free survival rate was 58.5% with anbenitamab plus HB1801 vs 34.4% with THP, representing a 54% reduction in the risk of disease progression or death (hazard ratio [HR] = 0.46; P < .001).
Study Details
The multicenter, open-label trial enrolled 885 patients with HER2-positive unresectable locally recurrent or metastatic breast cancer at 76 sites in China. Patients had received no prior chemotherapy or HER2-targeted therapy for advanced disease. Previous neoadjuvant or adjuvant therapy was permitted if disease progression occurred more than 12 months after treatment completion.
Patients were randomly assigned to receive anbenitamab plus HB1801 (n = 445) or THP (n = 440), administered intravenously every 3 weeks. The primary endpoint was progression-free survival as assessed by blinded independent central review. Secondary endpoints included objective response, duration of response, overall survival, and safety.
Baseline characteristics were generally balanced between the groups. Approximately 55% of patients had hormone receptor–positive disease, 71% had visceral metastases, and 37% had received prior neoadjuvant or adjuvant therapy.
Efficacy Outcomes
At the prespecified interim analysis, disease progression or death had occurred in 149 patients (33.5%) in the anbenitamab group and 252 patients (57.3%) in the THP group.
Estimated progression-free survival rates at 12 and 18 months were 80.2% and 66.9%, respectively, with anbenitamab plus HB1801, compared with 56.9% and 42.4% with THP.
The progression-free survival benefit was generally consistent across prespecified subgroups, including patients with prior trastuzumab exposure (HR = 0.47) and those with visceral metastases (HR = 0.47).
The confirmed objective response rate was 87.6% with anbenitamab plus HB1801 vs 73.4% with THP. Complete responses occurred in 3.8% and 2.3% of patients, respectively. Median duration of response had not been reached in the anbenitamab group compared with 16.6 months in the THP group.
The investigators noted that they could not determine whether the benefit resulted from a synergistic interaction between anbenitamab and HB1801, or from the individual contributions of the two agents.
Safety
Grade 3 or higher adverse events occurred in 45.9% of patients receiving anbenitamab plus HB1801 and 34.4% receiving THP; the most common were neutropenia (13.1% vs 8.4%) and leukopenia (9.7% vs 5.5%).
Serious adverse events occurred in 20.0% and 16.2% of patients, respectively. Adverse events led to treatment discontinuation in 5.2% of patients in the anbenitamab group and 3.4% in the THP group. Two patients in each group died from adverse events.
Although no new safety signals were identified, the authors emphasized the importance of longer-term safety data, particularly because first-line treatment may continue for an extended period.
The investigators identified several limitations, including enrollment exclusively in China, the open-label design, and relatively short follow-up. They also noted that trastuzumab deruxtecan plus pertuzumab—now approved for first-line treatment in the United States—was not used as the comparator because it had not been approved when the trial began.
“These positive findings suggest that anbenitamab plus HB1801 may offer a promising treatment option for these patients,” the authors concluded. However, overall survival data remain immature, and they noted that “longer follow-up will be essential to provide more definitive information.”
Binghe Xu, MD, PhD, of the National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, is the corresponding author.
DISCLOSURE: The trial was supported by Shanghai JMT-Bio Technology, with additional funding from Chinese national research programs and the National High Level Hospital Clinical Research Funding program. For full disclosures of the study authors, visit nejm.org.
