The addition of a potent oral AKT inhibitor to an already established treatment for breast cancer resulted in “significantly longer” progression-free survival, according to the results of a recent phase 2 clinical trial. 

Results of the FAKTION trial were published in The Lancet, after examining the addition of AZD5363 to fulvestrant in patients with aromatase inhibitor-resistant advanced breast cancer. The patient population for the study included postmenopausal women “with an Eastern Cooperative Oncology Group performance status of 0-2 and oestrogen receptor-positive, HER2-negative, metastatic or locally advanced inoperable breast cancer,” according to the authors. Participants had already had their condition either relapse or progress on an aromatase inhibitor. 

Doctor discussing treatment. Source: Getty

The 140 qualifying participating patients received either the drug combination or fulvestrant and placebo. The fulvestrant was administered every 28 days, while the AZD5363 or placebo was given twice daily, four days per week. The dosage continued until “disease progression, unacceptable toxicity, loss to follow-up or withdrawal of consent,” the authors said. The primary endpoint was progression-free survival with a one-sided alpha of .20. 

Study participants were enrolled between 2015 and 2018. By Jan. 30, 2019, 112 progression-free survival events were reported. Of those, 71% were reported in the AZD5363 group, compared to 89% in the placebo group. The median progression-free survival was 10.3 months (95% CI 5.0-13.2) in the dual-drug group, compared to 4.8 months (3.1-7-7) in the placebo group. 

The most common grade 3-4 adverse events reported were hypertension (32% vs. 24%), diarrhea (14% vs. 4%), and rash (20% vs. 0%). There were also serious adverse reactions in the AZD group, including acute kidney injury, diarrhea, and rash, among others. The authors said reported adverse events were “common, but manageable with dose reduction, and did not seem to compromise efficacy.” 

There was also one death reported, which researchers said could have been to the AZD5363 treatment. The patient died of atypical pulmonary infection. There was a second death in that group as well, though the cause had not been determined at the time of publication. 

“To our knowledge, this study is the first randomized trial to report on the addition of an AKT inhibitor to endocrine therapy in oestrogen receptor-positive metastatic breast cancer after previous aromatase inhibitor therapy,” the authors wrote. “The results showed an improvement in progression-free survival and response rate with the addition of capivasertib to endocrine therapy, suggesting synergy, in contrast to the poor efficacy in combination with aromatherapy,” the authors said. 

After the successful completion of this trial, the authors said they believe that “although of modest size, it provides rationale for a subsequent phase 3 trial.”