Anastrozole; Aromatase inhibitors; Breast neoplasms; Cyclin-dependent kinases; Immune checkpoint inhibitors; Neoadjuvant therapy; Nivolumab; Patient safety; Programmed cell death 1 receptor; ERBB2 protein, human; palbociclib; Receptor, ErbB-2; Receptors, Estrogen; Female; Humans; Neoadjuvant Therapy; Pneumonia; Antineoplastic Combined Chemotherapy Protocols/adverse effects; Breast Neoplasms/drug therapy; Antineoplastic Combined Chemotherapy Protocols; Surgery; Oncology; Cancer Research
Abstract :
[en] [en] 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.
Disciplines :
Oncology
Author, co-author :
Jerusalem, Guy ; Centre Hospitalier Universitaire de Liège - CHU > > Service d'oncologie médicale
Prat, Aleix; Department of Medicine, University of Barcelona, Hospital Clinic, IDIBAPS, c/ Rosselló, 149-153, 08036, Barcelona, Spain. Electronic address: alprat@clinic.cat
Reinisch, Mattea; Breast Unit Kliniken Essen-Mitte, Henricistrasse 40, 45136, Essen, Germany, Department of Gynecology with Breast Center Charité, Charitéplatz 1, 10117, Berlin, Germany. Electronic address: m.reinisch@kem-med.com
Saura, Cristina; Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology (VHIO), Centro Cellex, Carrer de Natzaret, 115, 117, 08035, Barcelona, Spain. Electronic address: csaura@vhio.net
Ruiz-Borrego, Manuel; Virgen del Rocío University Hospital, Av. Manuel Siurot, S/n, 41013, Sevilla, Spain. Electronic address: ruizborrego@gmail.com
Nikolinakos, Petros; University Cancer and Blood Center, 3320 Old Jefferson Rd, Bldg 700, Athens, GA, 30607, USA. Electronic address: pnikolinakos@universitycancer.com
Ades, Felipe ; Bristol Myers Squibb, 3401 Princeton Pike, Lawrence Township, Princeton, NJ, USA. Electronic address: felipe.ades@bms.com
Filian, Jeiry; Bristol Myers Squibb, 3401 Princeton Pike, Lawrence Township, Princeton, NJ, USA. Electronic address: jeiry.filian@bms.com
Huang, Ning; Bristol Myers Squibb, 3401 Princeton Pike, Lawrence Township, Princeton, NJ, USA. Electronic address: ning.huang@bms.com
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