Potency is clear, but for capivasertib, toxicity is an issue

CHICAGO – In a small study of postmenopausal women with estrogen receptor positive breast cancer, an AKT inhibitor added to fulvestrant demonstrated a significant benefit in progression free survival versus fulvestrant plus placebo — more than doubling time to progression.

That finding from the FAKTION trial was reported here in an oral abstract session on the final day of the American Society of Clinical Oncology meeting.

The investigator-led, phase II trial, which was conducted in England, randomly assigned patients 1:1 to fulvestrant 500 mg (day 1 and 15 of cycle 1 and day 1 only of subsequent 28 day cycles) and capivasertib 400 mg twice daily (n=69) or fulvestrant and placebo (n=71), said Robert Hugh Jones, MBBS, Velindre Cancer Centre and Cardiff University, Cardiff, U.K.

Capivasertib (AZD5363) is “a potent inhibitor of Akt1-3 isoforms,” Jones said, noting that it has shown synergistic activity with fulvestrant in pre-clinical studies.

Jones said that in an intention-t0-treat analysis the median PFS was 10.3 months for capivasertib compared to 4.8 months for placebo (hazard ratio (HR) 0.57; 95% CI: 0.39-0.84; one-sided P = 0.0017; two-sided P=0.0035).

The median overall survival was 26.0 months for capivasertib compared to 20.0 months for placebo, with a survival difference starting to emerge after 12 months, but it was not statistically significant.

Cesar A. Santa-Maria, MD, of Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, who served as discussant for the paper, noted that 39% of the patients in the capivasertib arm required dose reductions and 12% discontinued the study drug due to toxicity.

But Santa-Maria noted that the agent demonstrated activity regardless of PI3Kmut status, thus it is an investigational drug that should be further investigated in phase III studies.


The FAKTION trial was sponsored by the Velindre NHS Trust.

Hughes disclosed travel grants from Merck Serona Serbia.


Jones RH “Capivasertib (AZD5363) plus fulvestrant versus placebo plus fulvestrant after relapse or progression on an aromatase inhibitor in metastatic ER-positive breast cancer (FAKTION): A randomized, double-blind, placebo-controlled, phase II trial” ASCO 2019; Oral Abstract session, Breast Cancer – Metastatic June 4: Abstract 1005.

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