Current First-Line Treatment Landscape for mTNBC

Recent advancements in the treatment of first-line mTNBC have significantly shifted clinical perspectives, emphasizing the importance of early, optimized interventions. Given the aggressive nature of mTNBC and the high rate of attrition after progression, first-line therapy plays a critical role in prolonging survival and improving quality of life. Many patients may not receive further treatment due to rapid disease progression, loss to follow-up, or development of complications such as brain metastases. Consequently, clinicians aim to use the most effective treatment regimen from the outset, making the first-line decision particularly impactful.

Historically, the treatment standard for mTNBC has been chemotherapy, with the potential addition of immunotherapy based on biomarker status. The KEYNOTE-355 trial established this approach by demonstrating that the addition of pembrolizumab to chemotherapy significantly improved progression-free and overall survival in patients with PD-L1–positive disease (defined as combined positive score
≥10). This subgroup represents approximately 30% to 40% of the mTNBC population. For patients with PD-L1–negative tumors, chemotherapy remains the mainstay, and PARP inhibitors are considered for those with BRCA mutations—though this subgroup is relatively small, comprising less than 10% of cases.

Treatment selection is further informed by prior therapies received during early-stage disease. For instance, if patients were previously treated with taxanes but not with platinum agents, a regimen including carboplatin and gemcitabine may be preferred. However, for patients who received more intensive early-stage therapy (such as taxanes, anthracyclines, platinum, and pembrolizumab), clinicians may consider skipping conventional chemotherapy and proceeding directly to second-line agents such as antibody-drug conjugates (ADCs). Recent trial data, such as from the ASCENT-04 trial, have begun to explore whether ADCs might be viable as first-line therapy regardless of prior treatment, potentially reshaping future clinical approaches in mTNBC.