Work

Hormone therapy enhances anti-PD1 efficacy in premenopausal estrogen receptor-positive and HER2-negative advanced breast cancer

Year: 2024

Type: article

Abstract: The efficacy of immunotherapy for estrogen receptor-positive/HER2-negative (ER+/HER2−) metastatic breast cancer (MBC) has not been proven. We conduct a phase 1b/2 trial to assess the efficacy of combining pembrolizumab (anti-PD1 antibody), exemestane (nonsteroidal aromatase inhibitor), and leuprolide (gonadotropin-releasing hormone agonist) for 15 patients with premenopausal ER+/HER2− MBC who had failed one to two lines of hormone therapy (HT) without chemotherapy. The primary endpoint of progression-free survival rate at 8 months (i.e., 64.3%) is achieved. Moreover, 5 of the 14 evaluable subjects exhibited partial responses (overall response rate = 35.7%). The combination of anti-PD1 antibody and anti-hormone therapy is associated with an enhanced immunoreactive microenvironment influencing treatment efficacy, as observed in pre- and post-treatment tumor samples through NanoString analysis. Post-treatment tumors are associated with increased immune response and immune cells. The findings indicate that combining HT with anti-PD1 antibody is a promising treatment strategy for patients with premenopausal ER+/HER2− MBC. This study was registered at ClinicalTrials.gov ( NCT02990845 ). • HT increases anti-PD1 antibody efficacy in premenopausal ER+/HER2− MBC • HT plus anti-PD1 antibody increases immune cell infiltration and activation • Estrogen suppression plus immunotherapy activates ER+/HER2− tumor microenvironment Chen et al. demonstrate that the combination of hormone therapy and anti-PD1 antibody is effective in patients with premenopausal ER+/HER2− MBC. The combination treatment turns the tumor microenvironment into immunoactive status.

Source: Cell Reports Medicine

DOI: 10.1016/j.xcrm.2024.101879