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

BACKGROUND

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.

CASE: 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.

CONCLUSION

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.