Mario Campone, MD, Ph.D., Professor, Medical Oncologist, Director General of the Institut de Cancérologie de l’Ouest (ICO), René Gauducheau, St Herblain, France speaks about ESMO 2021 Abstract – 264P – AMEERA-1: Subgroup analyses of phase I/II study of amcenestrant (SAR439859), an oral selective estrogen receptor (ER) degrader (SERD), with palbociclib in postmenopausal women with ER+/ human epidermal growth factor receptor 2-negative (HER2–) advanced breast cancer (aBC).
264P – Abstract
Backstory:
Amcenestrant is an optimized, oral SERD that has showed promising anticancer activity in ER+/HER2– aBC when combined with palbociclib (palbo). Updated data, including anticancer activity by subgroups, is shown here.
Methodologies:
This phase 1/2 open-label study evaluated palbo 125 mg (21 days on, 7 days off) plus amcenestrant in ER+/HER2– aBC patients (pts) with less than 6 months of prior endocrine therapy in dose escalation (Part C; n = 15; 200 and 400 mg QD in 28-day cycles) and dose expansion (Part D; n = 30; 200 mg recommended phase 2 dose) in ER+/HER2– In response-evaluable pts without prior CDK4/6 or mTOR inhibitors (n = 35; Part C, n = 6; Part D, n = 29), antitumor activity was measured using the objective response rate (ORR; confirmed complete response [CR] and partial response [PR]) and clinical benefit rate (CBR; CR, PR, or stable disease [SD] 24 weeks) per RECIST v1.1. Subgroup analyses were carried out based on past therapy and baseline ESR1 mutation status (wild-type [wt] or mutant [m]). ddPCR and NGS were used to analyze ESR1 mutations and genomic profiling in cfDNA, respectively.
Outcomes:
The table shows the results of subgroup analysis (March, 2021 cut off). 7/8 pts with Y537S, D538G, E380Q, or Y537N baseline ESR1 mutations had CB, while 3/8 pts with D538G or E380Q had OR. In 33 pts with baseline NGS data, 23 had wtESR1 + other genomic aberrations, with OR in 6/23 (26.1%) and CB in 16/23 (69.6%); of 11/33 pts with OR, 8 pts had wtESR1 (including 1 pt with prior fulvestrant, PIK3CA, and PTEN) and 2 pts had no aberration; of 5/33 pts
Observations:
Regardless of ESR1 mutation status, amcenestrant coupled with palbociclib exhibited encouraging OR and CB in patients with ER+/HER2- aBC.
Clinical trial identification –
NCT03284957