Current Evidence and Future Directions

When a treatment already established in second- or third-line therapy is moved to the first line, it essentially becomes a sequencing question. Ideally, patients in the control group should have access to the drug at progression to fully understand its benefit. Some trials have incorporated this crossover design, allowing clearer interpretation of progression-free survival benefits in the first line without compromising overall survival data. However, not all studies provide such crossover, making it difficult to assess the true advantage of using these agents up front vs later. In diseases such as metastatic triple-negative breast cancer, where patients often experience rapid progression and treatment attrition, offering the most effective therapy early on is critical.

The future of treatment lies in better tailoring therapies through improved biomarkers that can predict which patients will benefit most from specific agents. Efforts are underway to profile tumors with advanced technologies to guide treatment decisions more precisely. This approach aims to identify patients who require ADCs in the first line and those who may safely delay their use until later. With ongoing research and emerging trial data, it is expected that targeted therapies will become more personalized, improving outcomes and minimizing unnecessary toxicity. Bringing ADCs into earlier stages of treatment, including curative settings, holds promise not only for prolonging survival but also for preventing metastatic disease altogether.

Although significant progress has been made, changing clinical practice takes time as new data mature. Current evidence supports using these agents earlier on in select patient populations, particularly those with specific biomarkers. Upcoming trials will clarify their optimal sequencing and combination strategies. Overall, the evolving landscape suggests a future where more patients with metastatic triple-negative breast cancer will experience meaningful treatment benefits and, ideally, long-term remission or cure. Continued research and clinical trial participation remain essential to realizing this potential and transforming patient outcomes in this challenging disease.