384MO - Final overall survival analysis for fulvestrant vs anastrozole in endocrine therapy (ET)-naïve, hormone receptor-positive (HR+) advanced breast cancer (FALCON)

Background

The phase 3 international, randomised, double-blind FALCON trial (NCT01602380) met its primary endpoint showing a statistically significant improvement in progression-free survival (PFS) with fulvestrant vs anastrozole as a first-line treatment for HR+ advanced breast cancer (BC). PFS improvement was confined to non-visceral disease (HR=0.59 [95% CI 0.42–0.84]) vs visceral disease (HR=0.99 [95% CI 0.74–1.33]). At the primary analysis, interim overall survival (OS) data were immature (31%). Here we report the prespecified final analysis of OS.

Methods

Postmenopausal women with ET-naïve, HR+/HER2– locally advanced or metastatic BC were randomised 1:1 to fulvestrant (500 mg, Days 0, 14 and 28, then monthly thereafter) or anastrozole (1 mg, daily). Secondary endpoints of OS, safety, and quality of life (QoL) are reported. The final OS analysis was triggered at a threshold of 65% maturity and ≥8 years since the last patient was enrolled, with an available 1-sided alpha of 0.01845.

Results

In the overall population (462 patients; 68% maturity; cut-off 11 July 2022), median OS was 44.8 months with fulvestrant vs 42.7 months with anastrozole (HR=0.97 [95% CI 0.77–1.21]; p=0.7579). Median OS across prespecified subgroups was consistent with the overall population. In patients with non-visceral disease, a 15% reduction in the risk of death was observed with fulvestrant vs anastrozole, although statistical significance was not reached (Table). No meaningful differences were seen in QoL. No new safety signals emerged. Table: 384MO

Median OS for visceral and non-visceral disease [DCO 11 July 2022]

CI, confidence interval; DCO, data cut-off; HR, hazard ratio; OS, overall survival.

Conclusions

At the final analysis of FALCON, no significant difference in OS was seen between fulvestrant and anastrozole in ET-naïve postmenopausal women with HR+/HER2– locally advanced or metastatic BC. The positive trend observed in OS for fulvestrant in non-visceral disease compared with visceral disease is consistent with the primary analysis.

Clinical trial identification

NCT01602380.

Editorial acknowledgement

Writing assistance was provided by Alison Lovibond PhD of BOLDSCIENCE Inc., funded by AstraZeneca.

Legal entity responsible for the study

AstraZeneca.

Funding

AstraZeneca.

Disclosure

J. Robertson: Financial Interests, Personal, Research Grant: AstraZeneca, Novartis; Financial Interests, Personal, Other, Personal fees are reported.: AstraZeneca. S. Noguchi: Financial Interests, Personal and Institutional, Advisory Role: AstraZeneca, Sysmex; Financial Interests, Personal, Invited Speaker: Pfizer, Eli Lilly; Financial Interests, Personal and Institutional, Funding: Chugai; Financial Interests, Personal and Institutional, Invited Speaker: Chugai, Sysmex; Financial Interests, Personal and Institutional, Royalties: Sysmex; Financial Interests, Personal and Institutional, Research Grant: Sysmex. S. Singh: Financial Interests, Institutional, Full or part-time Employment: AstraZeneca. S. Subramaniam, M.J. Ellis: Financial Interests, Personal and Institutional, Full or part-time Employment: AstraZeneca. All other authors have declared no conflicts of interest.