Durvalumab and tremelimumab before surgery in patients with hormone receptor positive, HER2-negative stage II-III breast cancer

Oncotarget. 2024 Mar 19:15:238-247. doi: 10.18632/oncotarget.28567.

Abstract

A clinical trial was conducted to assess the feasibility of enrolling patients with Stage II or III hormone receptor positive (HR+)/HER2-negative breast cancer to pre-operative dual PD-L1/CTLA-4 checkpoint inhibition administered prior to neoadjuvant chemotherapy (NACT). Eight eligible patients were treated with upfront durvalumab and tremelimumab for two cycles. Patients then received NACT prior to breast surgery. Seven patients had baseline and interval breast ultrasounds after combination immunotherapy and the responses were mixed: 3/7 patients experienced a ≥30% decrease in tumor volume, 3/7 a ≥30% increase, and 1 patient had stable disease. At the time of breast surgery, 1/8 patients had a pathologic complete response (pCR). The trial was stopped early after 3 of 8 patients experienced immunotherapy-related toxicity or suspected disease progression that prompted discontinuation or a delay in the administration of NACT. Two patients experienced grade 3 immune-related adverse events (1 with colitis, 1 with endocrinopathy). Analysis of the tumor microenvironment after combination immunotherapy did not show a significant change in immune cell subsets from baseline. There was limited benefit for dual checkpoint blockade administered prior to NACT in our study of 8 patients with HR+/HER2-negative breast cancer.

Keywords: ER positive; breast cancer; immunotherapy; neoadjuvant chemotherapy; tumor microenvironment.

MeSH terms

  • Antibodies, Monoclonal*
  • Antibodies, Monoclonal, Humanized*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Breast Neoplasms* / drug therapy
  • Breast Neoplasms* / pathology
  • Female
  • Humans
  • Neoadjuvant Therapy / adverse effects
  • Treatment Outcome
  • Tumor Microenvironment

Substances

  • durvalumab
  • tremelimumab
  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized