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Fulvestrant plus capivasertib versus placebo after relapse or progression on an aromatase inhibitor in metastatic, oestrogen receptor-positive, HER2-negative breast cancer (FAKTION): overall survival, updated progression-free survival, and expanded biomarker analysis from a randomised, phase 2 trial

  • 0The University of Manchester and The Christie NHS Foundation Trust, Manchester, UK.
The Lancet. Oncology +

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June 7, 2022

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June 7, 2022

View abstract on PubMed

Summary

This summary is machine-generated.

Capivasertib combined with fulvestrant improves survival for advanced ER-positive, HER2-negative breast cancer resistant to aromatase inhibitors. This benefit is most pronounced in patients with specific PI3K/AKT/PTEN pathway alterations in their tumors.

Area Of Science

  • Oncology
  • Pharmacology
  • Genetics

Background

  • Estrogen receptor (ER)-positive, HER2-negative advanced breast cancer often develops resistance to aromatase inhibitors.
  • Capivasertib, an AKT inhibitor, combined with fulvestrant, has shown potential in overcoming this resistance.
  • Previous studies suggested a benefit independent of PI3K/AKT/PTEN pathway alterations, but further investigation with advanced genetic testing was warranted.

Purpose Of The Study

  • To report updated progression-free survival (PFS) and overall survival (OS) data from the FAKTION trial.
  • To examine the impact of PI3K/AKT/PTEN pathway alterations, identified by expanded genetic testing, on treatment outcomes.
  • To evaluate the safety profile of capivasertib plus fulvestrant.

Main Methods

  • A randomized, double-blind, placebo-controlled, phase 2 trial involving postmenopausal women with advanced ER-positive, HER2-negative breast cancer resistant to aromatase inhibitors.
  • Participants received fulvestrant plus either capivasertib or placebo.
  • Tumor samples were analyzed using an expanded genetic testing panel, including next-generation sequencing, to identify PI3K/AKT/PTEN pathway alterations.

Main Results

  • Updated median PFS was 10.3 months with capivasertib plus fulvestrant versus 4.8 months with placebo (HR 0.56, p=0.0023).
  • Updated median OS was 29.3 months with capivasertib plus fulvestrant versus 23.4 months with placebo (HR 0.66, p=0.035).
  • In the subgroup with PI3K/AKT/PTEN pathway alterations, median PFS was 12.8 months with capivasertib versus 4.6 months with placebo (HR 0.44, p=0.0014), and median OS was 38.9 months versus 20.0 months (HR 0.46, p=0.0047). No significant benefit was observed in the pathway non-altered subgroup.

Conclusions

  • Capivasertib plus fulvestrant significantly improves PFS and OS in patients with advanced ER-positive, HER2-negative breast cancer resistant to aromatase inhibitors.
  • The benefit of capivasertib appears predominantly in patients with PI3K/AKT/PTEN pathway-altered tumors.
  • Further Phase 3 trials are needed to confirm these findings, particularly in patient populations not included in this study, such as those with prior CDK4/6 inhibitor exposure.