Window of opportunity trials with immune checkpoint inhibitors in triple-negative breast cancer

• Published in: ESMO open 2024-10, Vol.9 (10), p.103713, Article 103713
• Main Authors: Quintana, A., Saini, K.S., Vidal, L., Peg, V., Slebe, F., Loibl, S., Curigliano, G., Schmid, P., Cortes, J.
• Format: Article
• Language: English
• Subjects: immune checkpoint inhibitors; PD-L1; Review; triple-negative breast cancer; tumor-infiltrating lymphocytes; window of opportunity
• ISSN: 2059-7029; 2059-7029
• DOI: 10.1016/j.esmoop.2024.103713

Patients with triple-negative breast cancer (TNBC) have a relatively poor clinical outcome. The immune checkpoint inhibitor (ICI) pembrolizumab combined with chemotherapy is the current standard of care in TNBC patients with stage II and III. Monotherapy with ICIs has not been comprehensively assessed in the neoadjuvant setting in TNBC patients, given unfavorable results in metastatic trials. ICIs, however, have been tested in the window of opportunity (WOO) before surgery or standard chemotherapy-based neoadjuvant treatment. The WOO design is well suited to assess an ICI alone or in combination with other ICIs, targeted therapy, radiotherapy or cryotherapy, and measure their pharmacodynamic and clinical effect in this treatment-naive population. Some patients show a good response to ICIs in WOO studies. Biomarkers like tumor-infiltrating lymphocytes, programmed death ligand-1, and interferon-γ signature may predict activity and may identify patients likely to benefit from ICIs. Moreover, an increase in tumor-infiltrating lymphocytes, programmed death ligand-1 expression or T cell receptor expansion following administration of ICIs in the WOO setting could potentially inform of immunotherapy benefit, which would allow tailoring further treatment. This article reviews WOO trials that assessed immunotherapy in the early-stage TNBC population, and how these results could be translated to test de-escalation strategies of neoadjuvant chemotherapy and immunotherapy without compromising a patient’s prognosis. •Immune checkpoint inhibitors (ICIs) have not been adequately assessed in early triple-negative breast cancer (TNBC).•The window of opportunity (WOO) offers a niche to test ICIs alone or in combination and measure responses and biomarkers.•This article reviews and summarizes the results of different WOO trials with ICIs in TNBC.•Some patients responded very well to a few doses, allowing partial de-escalation of therapy without compromising prognosis.