Do the results of S0226 change your endocrine therapy of choice in denovo metastatic hormone positive breast cancer?

S0226 compared anastrozole to anastrozole plus fulvestrant loading dose in first-line treatment of metastatic ER-Positive Breast Cancer. The combination arm was more effective than anastrozole alone, with a significant improvement in PFS and OS. This concept of complete ER blockade has been an attractive preclinical and clinical concept (Massarweh et al, BCRT: 106:S115.SABCS,2007), but there are several limitations to the conclusions from the SWOG S0226 study.

First, there was no fulvestrant-only control arm in S0226, and another study (FACT) failed to show superiority of combined fulvestrant and AI vs an AI alone (Bergh et al, JCO 2012) in first line. Subsequently, the FIRST study, showed an improved OS with fulvestrant single agent over a...

S0226 is the only phase-III study to show overall survival advantage in first-line, largely endocrine-naïve patient population, currently. FACT required patients to be in first relapse; therefore, included largely endocrine-pretreated population, with more endocrine-pretreated patients and patients with liver metastases in the combination arm. Furthermore, the OS difference between FACT (median 38 months in both arms) and S0226 (median 42 months and 50 months in the 2 arms) attest to the differing patient populations in FACT and S0226. These OS survival data in S0226 were better than predicted at 36 months and 48 months, respectively, and thus a higher bar was crossed. Still, this benefit of fulvestrant addition retained statistical and cli...

Although I acknowledge that the results are quite good with combination, most of our group has pursue the path of CDK 4,6 Inhibitors together with AI with no direct comparison available