A Phase III, Randomized, Open-label, Multicenter Study Evaluating the Efficacy and Safety of Adjuvant Giredestrant Compared with Physician's Choice of Adjuvant Endocrine Monotherapy in Patients with Estrogen Receptor-Positive, HER2-Negat

Endocrine therapy with tamoxifen or aromatase inhibitors (AIs [with or without ovarian function suppression (OFS)]) are currently the main endocrine treatment options for estrogen receptor?positive (ER+) early breast cancer (EBC). Despite the effectiveness of available therapies, many patients ultimately experience disease relapse or develop resistance to these agents (Angus et al. 2017). In addition, treatment-associated toxicity is an important major barrier to the full application of the current cancer treatment leading to treatment discontinuation in many patients (Partridge et al. 2008; Hershman et al. 2010). Consequently, there is a critical need for more optimal adjuvant therapy in patients with ER+ EBC, particularly for patients who have a high likelihood of recurrence. Small-molecule, selective estrogen receptor degraders (SERD) are recognized as a therapeutic approach in patients with ER+ metastatic breast cancer (MBC). Fulvestrant, a first-generation?approved SERD, has shown statistically significant improvement in progression-free survival (PFS) compared with anastrozole in front-line patients, as demonstrated in the FALCON study (NCT01602380; Robertson et al. 2016). Although fulvestrant demonstrated clinical benefit in MBC, unfavorable pharmacokinetic (PK) properties and a requirement for intramuscular (IM) injection have hindered further development of this drug in EBC. Oral SERDs may provide a more tolerable treatment option that enables better adherence and thus maximizes therapeutic benefit and compliance. Giredestrant (GDC-9545) is a potent, orally bioavailable SERD with a known mode of action, which parallels fulvestrant’s mechanism of action (MoA). On the basis of its MoA, nonclinical, and clinical activity profile, giredestrant has the potential to be an important new drug for the treatment of patients with ER+ breast cancer and support development of giredestrant in EBC in addition to the ongoing development in MBC.