Novel Antibody-Drug Conjugates Cut Progression Risk by Over 70 Percent in HER2-Low Breast Cancer

On October 23, 2026, researchers at the European Society for Medical Oncology (ESMO) Congress in Madrid unveiled pivotal Phase III data for two novel antibody-drug conjugates. The therapies, rolditamig deuderuxtecan and trastuzumab rezetecan, both reduced the risk of disease progression or death by more than 70 percent in patients with HER2-low metastatic breast cancer.[1][3][4]

The dual presentations mark a major expansion in how oncologists approach the disease. HER2-low breast cancer is defined as tumors that show a faint but detectable presence of the HER2 protein on their surface. This category represents nearly 60 percent of all breast cancer cases globally.[7]

Historically, these tumors were classified simply as HER2-negative because they did not respond to traditional HER2-blocking monoclonal antibodies. Patients whose disease progressed after standard endocrine therapies were left with conventional chemotherapy as their primary remaining option, which often yielded limited benefits and systemic toxicity.[4]

Antibody-drug conjugates, or ADCs, bypass that limitation by using the HER2 receptor merely as a doorway rather than a signaling pathway to block. The antibody binds to the cell surface and acts as a homing beacon. It then delivers a highly potent chemotherapy payload directly inside the tumor cell.[4][7]

The APEX-Breast01 Trial

The APEX-Breast01 trial evaluated rolditamig deuderuxtecan, also known by its developmental name TQB2102, against standard physician's choice chemotherapy. The study enrolled patients who had not previously received chemotherapy for their advanced disease. Most participants had hormone receptor-positive tumors that had progressed after standard endocrine treatments.[3][7]

The targeted therapy nearly tripled the time patients lived without their disease worsening. Median progression-free survival reached 16.4 months for those receiving the ADC, compared with just 5.5 months for the chemotherapy group. This translated to a 71 percent reduction in the hazard of progression or death.[1][3][7]

"Rolditamig deuderuxtecan demonstrated a statistically significant and clinically meaningful improvement in PFS and a clear trend toward OS benefit versus chemotherapy," reported Shusen Wang, MD, of the Sun Yat-sen University Cancer Center in Guangzhou, China, during the presentation.[1][7]

The objective response rate for the overall HER2-low population was 68.8 percent with the ADC, more than double the 31.0 percent seen with chemotherapy. The drug's architecture is unique: it uses a biparatopic design, meaning it binds to two distinct, non-overlapping regions of the HER2 receptor simultaneously.[1][3][7]

This dual-binding approach is intended to increase receptor cross-linking and pull more of the drug into the cell. Researchers believe this mechanism improves the delivery of the topoisomerase-I inhibitor payload, particularly in tumors where HER2 expression is heterogeneous or relatively sparse.[3][7]

The HORIZON-Breast06 Trial

A second Phase III trial, HORIZON-Breast06, tested a different ADC called trastuzumab rezetecan in a similar patient population. The results, which were simultaneously published in the journal JAMA, mirrored the dramatic improvements seen with TQB2102. The trial enrolled 551 patients across multiple centers in China.[4][5][6]

In the overall population, median progression-free survival reached 16.4 months for those receiving trastuzumab rezetecan, compared with 6.8 months for those on standard chemotherapy. This represented a 73 percent relative reduction in the hazard of progression or death, establishing a clear superiority over older regimens.[4][5][6]

The benefit remained remarkably consistent across different tumor subtypes. Patients with hormone receptor-positive disease saw their median progression-free survival extend to 16.4 months. Crucially, patients with hormone receptor-negative disease experienced a nearly identical benefit, reaching 16.5 months compared to 6.8 months on chemotherapy.[4][5]

The objective response rate for trastuzumab rezetecan was 75.5 percent, vastly outperforming the 41.2 percent response rate achieved by standard chemotherapy. The median duration of that response extended to 15.0 months, providing patients with a prolonged period of disease control without the need for alternative interventions.[4][5][6]

Safety and the Evolving Landscape

Safety profiles for both medications were manageable, though they carried distinct side effects requiring clinical monitoring. In the APEX-Breast01 trial, the incidence of treatment-related interstitial lung disease—a dangerous lung inflammation associated with some ADCs—was remarkably low at just 2.2 percent, with no related fatalities.[7]

The HORIZON-Breast06 trial reported a similarly low 2.5 percent rate of interstitial lung disease. However, patients receiving trastuzumab rezetecan experienced higher rates of hematologic toxicity. Severe drops in neutrophil counts occurred in 65.2 percent of patients on the ADC, compared to 54.2 percent on standard chemotherapy.[5][6]

The dual presentations signal a rapid shift in the breast oncology landscape. Until recently, trastuzumab deruxtecan, marketed as Enhertu, was the only approved ADC specifically indicated for HER2-low metastatic breast cancer. It established the clinical relevance of the HER2-low classification and transformed standard care.[3][4]

The emergence of two highly effective alternatives introduces genuine competition into the space. Oncologists anticipate that having multiple ADCs available will eventually allow them to sequence the drugs. If a tumor develops resistance to one ADC's specific linker or payload, doctors might successfully switch to another.[4]

Overall survival data for both trials remains immature, meaning researchers do not yet know exactly how much the drugs extend total lifespan. However, early statistical trends in both studies strongly favor the antibody-drug conjugates over traditional chemotherapy, and longer-term follow-up is already underway.[1][3][4][6]

As these therapies move toward regulatory review, their success underscores a broader victory in cancer research. By turning a faint protein expression into a therapeutic vulnerability, scientists have fundamentally rewritten the prognosis for the majority of metastatic breast cancer patients, offering durable control where few options previously existed.[1][4]