ICIs Exceptional Long Response in TNBC: Addressing the Issue of Optimal ICIs Duration. Two Cases and Review of the...

Breast cancer is the leading cause of cancer-related mortality in women, with triple-negative breast cancer (TNBC) being an aggressive subtype associated with poor prognosis and limited treatment options. TNBC is known for its immunogenic characteristics, including high genetic instability and elevated tumor-infiltrating lymphocytes (TILs). Immune checkpoint inhibitors (ICIs) have shown efficacy in TNBC treatment, but the optimal treatment duration in case of prolonged response remains unclear.

This case series here reported presents two patients with metastatic TNBC who demonstrated an excellent response to ICI therapy. The first patient, a 60-year-old, was enrolled in a Phase I clinical trial and received a combination of anti-PD-1, anti-LAG-3, and anti-CSF-1 monoclonal antibodies. The second patient, a 45-year-old with BRCA1-mutated TNBC, participated in a Phase II trial and received a combination of avelumab (anti-PD-L1) and talazoparib (PARP inhibitor). Both patients achieved a complete radiological response (CR), which has been maintained for 5 years. A literature review performed here identified seven additional long-term ICI responders in metastatic TNBC. While ICIs showed significant efficacy in some patients, variability in PD-L1 expression and TILs suggests that other factors may influence response. Two patients in previous studies discontinued ICIs after 2 years without progression, prompting questions about the optimal treatment duration.

ICIs optimal treatment duration remains uncertain. Literature on metastatic melanoma suggests that discontinuing ICIs after a complete response rarely leads to recurrence. Prospective studies and emerging biomarkers, such as circulating tumor DNA, may help tailor treatment decisions.