Evaluating the ASCENT-04 Trial Results in Triple-Negative Disease

The ASCENT-04 trial findings established SASE plus pembrolizumab as a new standard of care for first-line metastatic triple-negative breast cancer, demonstrating superior progression-free survival and trending toward overall survival improvement compared with standard chemotherapy plus pembrolizumab. The combination showed robust clinical activity with manageable toxicity, supported by a well-designed study with appropriate crossover considerations. This represents a significant advancement in triple-negative breast cancer treatment, offering an antibody-drug conjugate (ADC)–based approach as first-line therapy.

Prior immunotherapy exposure influences treatment decisions, though the study included a limited number of patients with previous pembrolizumab exposure. For patients who completed adjuvant pembrolizumab more than 6 months prior, SASE plus pembrolizumab remains a reasonable consideration, though this represents clinical judgment without definitive data on optimal timing intervals. The question parallels similar sequencing challenges with CDK4/6 inhibitors and other targeted therapies moving from metastatic to adjuvant settings.

The evolving landscape includes additional ADCs in development for triple-negative breast cancer, such as datopotamab deruxtecan being studied in the TROPION-Breast03 trial for residual disease settings. As active drugs advance from metastatic to early-stage applications, sequencing questions will become increasingly complex. Clinicians must navigate these decisions based on individual patient factors, disease characteristics, and treatment-free intervals while awaiting more definitive sequencing data from ongoing and future clinical trials.