A double-blind placebo controlled randomized phase III trial of fulvestrant and ipatasertib as treatment for HER-2 negative and estrogen receptor positive (ER+) metastatic breast cancer (MBC): Overall survival results of the CCTG/BCT MA.40/FINER study

MA.40/FINER

Paciente / Población Intervención / Exposición Comparación Desenlace

In patients with ER+/HER2-negative metastatic breast cancer progressing after a CDK4/6 inhibitor plus aromatase inhibitor, ipatasertib plus fulvestrant did not improve overall survival compared with placebo plus fulvestrant.

N

250pacientes

Diseño

Phase III, double-blind, placebo-controlled trial randomising pre-, peri- and postmenopausal women and men with ER+/HER2-negative metastatic breast cancer progressing on a CDK4/6 inhibitor plus aromatase inhibitor 1:1 to ipatasertib plus fulvestrant vs placebo plus fulvestrant, stratified by AKT pathway alteration on cfDNA and primary vs secondary endocrine resistance (NCT04650581).

Desenlace

Investigator-assessed progression-free survival in the ITT population. Overall survival, reported here, was a secondary endpoint.

ResultadoMedian overall survival in the ITT population 26.68 mo (95% CI 21.42-30.78) with ipatasertib vs 25.76 mo (95% CI 19.98-28.88) with placebo (HR 0.97, 95% CI 0.70-1.33; P = 0.83). In the exploratory AKT pathway-altered cohort, median overall survival 23.66 mo (95% CI 18.53-28.65) vs 25.23 mo (95% CI 16.99-28.88) (HR 1.14, 95% CI 0.72-1.80; P = 0.58). At a median follow-up of 35.0 mo, 3.2% vs 2.4% remained on protocol treatment. No new safety signals were observed with longer follow-up.

Redfern AD, Chia SK, Ayoub J, et al. Presented at ESMO Congress 2026, abstract LBA14, 24 October. Not yet published.

Discusión y crítica

This blinded, placebo-controlled trial shows that the progression-free survival gain previously reported for ipatasertib did not carry over into overall survival, either overall or in the AKT pathway-altered cohort. With a median follow-up of 35.0 months and almost all participants off protocol treatment, the overall survival data look mature, but overall survival was a secondary endpoint in a trial of 250 patients and the AKT-altered result is exploratory. The abstract does not report the number of deaths, subsequent therapies that might dilute an overall survival effect, the progression-free survival figures themselves or any detailed adverse event rates. The study was led by the Canadian Cancer Trials Group, with funding from the Canadian Cancer Society and F. Hoffmann-La Roche Ltd.