Antibody-drug conjugates (ADCs) that target Trop2 have emerged as promising candidates for the first-line treatment of metastatic triple-negative breast cancer (TNBC) in patients who are not suitable for immunotherapy, as indicated by two pivotal randomized trials presented at a recent conference in Berlin.
Patients who received datopotamab deruxtecan (Dato-DXd, Datroway) experienced a nearly twofold increase in median progression-free survival (PFS), with durations of 10.8 months compared to 5.6 months for those treated with chemotherapy. Additionally, overall survival (OS) improved by five months for the Dato-DXd group. In a separate trial, individuals treated with sacituzumab govitecan (Trodelvy) showed a nearly 40% enhancement in median PFS compared to chemotherapy, with durations of 9.7 months versus 6.9 months. However, preliminary OS analysis did not reveal significant disparities between the treatment groups.
During a discussion on the findings at the European Society for Medical Oncology congress, Ana Garrido-Castro, MD, from the Dana-Farber Cancer Institute in Boston, emphasized the importance of these studies in shifting the treatment paradigm for metastatic TNBC, particularly given the dire prognosis associated with standard chemotherapy. “With a significant number of patients failing to survive beyond six months on conventional chemotherapy, we should prioritize the use of a Trop2 ADC as the first-line therapy,” she stated. “The choice of ADC may depend on various factors, such as disease burden, side effects, and patient preferences.” She concluded that these trials advocate for Trop2 ADC therapy as the preferred first-line approach for this patient demographic.
The trials address a critical gap in treatment options for metastatic TNBC, the most aggressive subtype of breast cancer, which has historically offered limited therapeutic alternatives. Rebecca Dent, MD, from the National Cancer Center of Singapore, who shared the results of the Dato-DXd study (TROPION-Breast02), noted that standard first-line treatment typically involves immunotherapy with a PD-(L)1 inhibitor. However, approximately 70% of patients are ineligible for such therapies, and nearly half do not progress beyond the first-line treatment.
In the TROPION-Breast02 trial, researchers enrolled patients with untreated, inoperable, or metastatic TNBC who could not receive PD-(L)1 therapy. These patients were randomized to receive Dato-DXd or chemotherapy as determined by the investigator. Subsequent treatments, including approved ADCs, were available upon disease progression at the discretion of the investigator. The trial”s primary endpoints were OS and PFS, assessed by a blinded independent committee review (BICR).
The analysis included 644 patients with a median age between 56 and 57. Approximately one-third had de novo metastatic TNBC, while 20% had a prior disease-free interval of 12 months or fewer. Almost half of the participants had a disease-free interval exceeding 12 months, and around 80% presented with visceral metastases. After a median follow-up of 27.5 months, the primary results demonstrated a 43% reduction in the risk of disease progression or death for patients receiving Dato-DXd.
In the study involving sacituzumab govitecan, after a median follow-up of 13.2 months, the primary analysis revealed a 38% reduction in the PFS hazard for those treated with the ADC. The findings indicated that nearly half the patients in both groups achieved objective responses, though the median duration of response was significantly longer in the sacituzumab cohort. The OS metrics were similar for both treatment arms, with median values around 20-21 months.
Overall, the data from these trials suggest that Trop2-targeted ADCs could redefine the treatment landscape for metastatic TNBC, especially for patients unable to access immunotherapy. The research contributes to a growing understanding of effective treatment strategies for this challenging breast cancer subtype.
