Elacestrant

Carrick Therapeutics' CDK7 inhibitor samuraciclib demonstrated significantly extended progression-free survival in HR+ advanced breast cancer patients without TP53 mutations or liver metastases in two independent Phase 2 trials.

The EMERALD trial demonstrated that patients with ESR1-mutant metastatic breast cancer who received CDK4/6 inhibitor therapy for more than 12 months achieved significantly better outcomes with elacestrant, with median progression-free survival of 8.6 months versus 3.8 months in optimal patients.

ESR1 mutations are rare (<5%) in newly diagnosed breast cancer but develop in 30-40% of patients after aromatase inhibitor therapy, enabling tumors to remain active without estrogen.

• Sanofi discontinues the development of amcenestrant, an oral selective estrogen receptor degrader (SERD), after it failed in the AMEERA-5 phase 3 trial. • The AMEERA-5 trial compared amcenestrant plus palbociclib to letrozole plus palbociclib as a first-line treatment for HR-positive/HER2-negative advanced breast cancer. • This failure raises concerns about the potential of SERDs in the first-line treatment of breast cancer, impacting other developers in the field. • Sanofi will discontinue all amcenestrant studies, including the AMEERA-6 trial in early-stage HR+ breast cancer patients.

• The phase 3 FALCON trial's final overall survival (OS) analysis showed no significant difference between fulvestrant and anastrozole in endocrine therapy-naive, HR-positive advanced breast cancer. • Median OS was 44.8 months for fulvestrant versus 42.7 months for anastrozole (HR, 0.97; P = .76), with a median follow-up of 37.1 months. • A trend toward improved survival with fulvestrant was observed in patients with nonvisceral disease (median OS 65.2 months vs 47.8 months; HR, 0.85). • Post-hoc analysis revealed greater OS improvement with fulvestrant in nonvisceral vs. visceral disease subgroups compared to anastrozole.