Neoadjuvant nivolumab + palbociclib + anastrozole for oestrogen receptor-positive/human epidermal growth factor receptor 2-negative primary breast cancer: Results from CheckMate 7A8

Breast. 2023 Dec:72:103580. doi: 10.1016/j.breast.2023.103580. Epub 2023 Sep 15.

Abstract

Background: Preclinical data suggest synergistic activity with the combination of programmed death-1 and cyclin-dependent kinase 4/6 blockade in oestrogen receptor-positive/human epidermal growth factor 2-negative (ER+/HER2-) breast cancer. The noncomparative phase 1b/2 CheckMate 7A8 study (NCT04075604) evaluated neoadjuvant treatment with nivolumab, palbociclib, and anastrozole in patients with ER+/HER2- breast cancer. Here, we report outcomes from the safety run-in phase.

Methods: Patients with histologically confirmed, untreated ER+/HER2- breast cancer, primary tumour ≥2 cm, ECOG performance status ≤1, and eligible for post-treatment surgery received nivolumab 480 mg intravenously every 4 weeks, palbociclib 125 mg or 100 mg orally once daily for 3 weeks per cycle, and anastrozole 1 mg orally once daily for five 4-week cycles, or until disease progression. The primary endpoint was the proportion of patients with dose-limiting toxicities (DLTs) within 4 weeks of treatment initiation.

Results: At safety data review, 21 patients were treated (palbociclib 125-mg group: n = 9; palbociclib 100-mg group: n = 12). DLTs were reported in 2 (22.2%) and 0 patients in the palbociclib 125-mg and 100-mg groups, respectively. Across both groups, 9 patients discontinued treatment due to toxicity (grade 3/4 hepatic adverse events [n = 6], grade 3 febrile neutropaenia [n = 1], grade 1 pneumonitis [n = 1], and grade 3 rash and grade 2 immune-mediated pneumonitis [n = 1]). Consequently, the study was closed early.

Conclusions: Neoadjuvant treatment with nivolumab, palbociclib, and anastrozole showed a high incidence of grade 3/4 hepatotoxicity and treatment discontinuation, indicating that this combination should not be further pursued for treatment of primary ER+/HER2- breast cancer.

Keywords: Anastrozole; Aromatase inhibitors; Breast neoplasms; Cyclin-dependent kinases; Immune checkpoint inhibitors; Neoadjuvant therapy; Nivolumab; Patient safety; Programmed cell death 1 receptor.

Publication types

  • Clinical Trial, Phase II
  • Clinical Trial, Phase I

MeSH terms

  • Anastrozole
  • Antineoplastic Combined Chemotherapy Protocols* / adverse effects
  • Breast Neoplasms* / drug therapy
  • Female
  • Humans
  • Neoadjuvant Therapy
  • Nivolumab
  • Pneumonia
  • Receptor, ErbB-2
  • Receptors, Estrogen

Substances

  • Anastrozole
  • ERBB2 protein, human
  • Nivolumab
  • palbociclib
  • Receptor, ErbB-2
  • Receptors, Estrogen