CR1447 is a novel transdermal formulation of 4-OH-Testosterone with aromatase inhibiting properties and androgen receptor modulation. Phase I data demonstrated efficacy and a favorable toxicity profile. In this trial efficacy and toxicity cohort A (A) with estrogen-receptor positive disease and cohort B (B) with androgen-receptor positive triple negative metastatic breast cancer was investigated.
Based on the phase I data, a dose of 400 mg was topically administered on both thighs every day. Primary endpoint was disease control rate at week 24 (DC24). The goal is to show that disease control at 24 weeks (DC24) of > 30% (A) and >15 % (B). In (A) patients (pts) with a maximum of one line of endocrine therapy for advanced disease (AD) for at least six months without progression were eligible (N = 21). Eight pts were excluded because they did not fulfill these criteria. In (B) up to two prior lines of chemotherapy for AD were allowed.
After registration of 37 pts (A)=29 and (B)=8, accrual was stopped after an interim analysis due to futility in (A) and slow accrual in (B). DC24 was reached in 5 out of 21 eligible pts (24%) in (A) and 0% in (B). In (A) eight pat were ineligible due to amendment of inclusion criteria. In (A) median PFS of eligible pts was 5.1 months (m) (95% CI: 2.5-5.6) and 2.6 months (95% CI: 2.1-2.9) in non-eligible pts. In (B) median PFS was 2.5 m (95% CI 0.7-2.6). Median OS of eligible pts in (A) was 24.6 m (95% CI 22.9-NA) and in (B) 10.8 m (95% CI 3.3-10.9). QoL assessed by FACT-ES questionnaire at baseline, week 4 and 24 showed no deterioration under treatment. CR1447 had a favorable safety profile without treatment related grade 3-5 toxicities in stratum A. Most common treatment related toxicities were: hypertriglyceridemia (60%), aspartate aminotransferase increased (51%) and dry skin (46%).
CR1447 is an innovative endocrine therapy with a favorable safety profile. Despite not reaching the primary endpoint (DC24 in 30% of patients), the DC24-rate of 24% in the 2nd-line setting and one patient in prolonged PR are a signal of activity. Further evaluation in a truly endocrine sensitive population is warranted.
NCT02067741.
SAKK Switzerland.
Curadis, Erlangen, Germany.
All authors have declared no conflicts of interest.