Fulvestrant–Capivasertib Combo Significantly Prolongs Survival in ER-Positive Breast Cancer

Phase 2 study findings showed that adding capivasertib to fulvestrant therapy significantly extended progression-free survival (PFS) over placebo plus fulvestrant in patients with metastatic, estrogen receptor (ER)-positive breast cancer (Lancet Oncol. 2020 Feb 5. Epub ahead of print).

“The FAKTION trial investigated whether the addition of capivasertib to fulvestrant improved…PFS…in patients with aromatase inhibitor-resistant advanced breast cancer,” explained lead investigator Robert H. Jones, MRCP, Department of Cancer and Genetics, Cardiff University, United Kingdom, and colleagues.

A total of 140 postmenopausal patients with estrogen receptor–positive, HER2-negative, metastatic or locally advanced, inoperable breast cancer that relapsed or progressed during therapy with an aromatase inhibitor were enrolled in the study between March 16, 2015, and March 6, 2018.

Patients in the double-blind, placebo-controlled were collected from 19 hospitals across the United Kingdom. They were then randomized in a 1:1 ratio to receive fulvestrant 500 mg every 28 days plus capivasertib 400 mg (n = 69) or matching placebo (n = 71) twice daily on an intermittent weekly schedule. Treatment was administered until disease progression, unacceptable toxicity, loss to follow-up, or withdrawal of consent occurred.

The primary end point of the study was PFS with a 1-sided alpha of 0.20, and PFS follow-up lasted for a median of 4.9 months.

As of January 30, 2019 (the point of primary analysis for PFS), 112 PFS events had occurred, including 49 (71%) in the capivasertib arm and 63 (89%) in the placebo arm. The median PFS was 10.3 months (95% CI, 5.0-13.2) versus 4.8 months (95% CI, 3.1-7.7) in the capivasertib and placebo arms, respectively, providing an unadjusted hazard ratio of 0.58 (95% CI, 0.39-0.84) in favor of capivasertib (2-sided P = .0044; 1-sided log rank test P = .0018).

The most frequently reported grade 3-4 adverse events were hypertension (32% in the capivasertib arm vs 24% in the placebo arm), diarrhea (14% vs 4%, respectively), rash (20% vs 0%, respectively), infection (6% vs 3%, respectively), and fatigue (1% vs 4%, respectively).

Only patients in the capivasertib arm had serious adverse events, including acute kidney injury, diarrhea, rash, hyperglycemia, loss of consciousness, sepsis, and vomiting.

One patient death from atypical pulmonary infection was deemed possibly related to capivasertib therapy. A second death in the capivasertib arm had an unknown cause, whereas all other mortalities in both arms were disease-related (19 in the capivasertib arm and 31 in the placebo arm).

“[PFS] was significantly longer in participants who received capivasertib than in those who received placebo. The combination of capivasertib and fulvestrant warrants further investigation in phase 3 trials,” Dr Jones and colleagues concluded.—Hina Porcelli