92MO Neoadjuvant nivolumab (NIVO) + palbociclib (PALBO) + anastrozole (ANA) for estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2−) primary breast cancer (BC): CheckMate 7A8

Abstract

Cyclin-dependent kinase (CDK) 4/6 inhibition + ER signaling blockade is a highly effective treatment option for metastatic ER+/HER2− BC. Preclinical studies show evidence of CDK 4/6 and programmed death-1 (PD-1) blockade synergy. CheckMate 7A8, a non-comparative, phase 2 study, evaluated neoadjuvant NIVO + PALBO + ANA in patients (pts) with ER+/HER2− primary BC. Here, we report safety outcomes from the safety run-in phase. Eligible pts were men or postmenopausal women with newly diagnosed, histologically confirmed, untreated ER+/HER2− BC with primary tumor ≥ 2 cm, an ECOG performance status of 0/1, and eligible for post-treatment surgery. Pts received NIVO 480 mg IV every 4 wks (1 cycle), PALBO 125 mg (dose level [DL] 1) or 100 mg (DL 2) PO once daily (QD) for 3 wks per cycle, and ANA 1 mg PO QD, for 5 cycles total/until disease progression. Primary endpoint (safety run-in phase) was the number of pts with occurrence of dose-limiting toxicity (treatment-emergent adverse events [AEs] within 4 wks of treatment start). As of safety data review on 6 May 2021, 21 pts (DL 1: n = 9; DL 2: n = 12) were treated. Most common grade ≥3 treatment-related AEs (TRAEs) were elevated alanine or aspartate aminotransferase, neutropenia, and decreased white blood cell count in DL 1 (n = 2 each; 22.2%), and decreased neutrophil count (n = 5; 41.7%) in DL 2. 5 pts (DL 1) and 4 pts (DL 2) discontinued treatment due to toxicity, mainly grade ≥3 hepatic TRAEs (Table). The study was closed on 27 July 2021 after safety run-in ended. Additional safety and preliminary efficacy data (database lock: 3 February 2022) will be presented.Table: 92MOTRAEs leading to discontinuation, n (%)Dose level 1 (n = 9)Dose level 2 (n = 12)Any gradeGrade 3/4Any gradeGrade 3/4Increased ALT2 (22.2)2 (22.2)1 (8.3)1 (8.3)Hypertransaminasaemia001 (8.3)1 (8.3)Increased AST2 (22.2)2 (22.2)00Increased transaminases1 (11.1)1 (11.1)01 (8.3)Febrile neutropenia1 (11.1)1 (11.1)00Rash1 (11.1)1 (11.1)00Pneumonitis1 (11.1)01 (8.3)0 Open table in a new tab Neoadjuvant NIVO + PALBO + ANA showed a higher incidence of grade ≥3 hepatic TRAEs than historical single-agent safety profiles. These findings show a potential safety risk for the use of endocrine therapy with PD-1 + CDK 4/6 blockade.