A significant portion of patients (30-50%) with metastatic triple-negative breast cancer do not survive to receive second-line treatment. This high attrition rate underscores the critical importance of administering the most effective therapy—offering the best PFS and response rate—in the first-line setting to maximize patient outcomes.
Antibody-drug conjugates (ADCs) can cause immunogenic cell death, remodeling the tumor microenvironment and enhancing antigen presentation. This mechanism could potentially make PD-L1 negative ('cold') tumors responsive to immune checkpoint inhibitors, creating a strong rationale for investigating ADC-immunotherapy combinations in this patient population.
For patients with lung metastases and symptoms like shortness of breath, choosing an ADC becomes complex. The primary concern is the inability to distinguish between disease progression and drug-induced interstitial lung disease (ILD), a known risk with certain ADCs. This diagnostic ambiguity can lead clinicians to favor ADCs with a lower ILD risk profile.
The ASCENT-03 and -04 trials featured a high rate of crossover, with over 80% of patients in the chemotherapy arm receiving Sacituzumab Govitecan (SG) upon progression. This ethical trial design confounds the overall survival (OS) data, making the observed OS benefit appear smaller than the drug's true potential if used exclusively in the first-line setting.
Managing side effects of antibody-drug conjugates is not one-size-fits-all. Sazetuzumab-govatecan requires managing GI issues, while Datopotamab-deruxtecan has unique risks like ophthalmologic problems and ILD, necessitating pre-treatment specialist evaluation. Proactive patient education and tailored mitigation are key to maintaining treatment continuity and efficacy.