persevERA Breast Cancer (BC): Phase III study evaluating the efficacy and safety of giredestrant (GDC-9545) palbociclib versus letrozole plus palbociclib in patients (pts) with estrogen-receptor-positive, HER2-negative locally advanced or metastatic BC (ER /HER2-LA/mBC).

Abstract

TPS1103 Background: Modulating estrogen synthesis and/or ER activity is the mainstay of treatment for pts with ER+ BC. Despite substantial progress, many pts experience relapse during/after adjuvant endocrine therapy. However, even though resistant to aromatase inhibitors (AIs) or tamoxifen, growth and survival of the majority of tumors are thought to remain dependent on ER signaling. Therefore, pts with ER+ BC can still respond to second- or third-line endocrine treatment after progression on prior therapy (Di Leo 2010; Baselga 2012). Therapeutic resistance can arise from mutations in ESR1, which can drive estrogen-independent transcription and proliferation. The highly potent, non-steroid..