ATLANTACombining the investigational aromatase inhibitor atamestane with the estrogen-blocker toremifene (Fareston) in an attempt to achieve "complete estrogen blockade" did not improve time to progression (TTP) in patients with advanced breast cancer, compared with aromatase inhibitor monotherapy with letrozole (Femara). Paul E. Goss, MD, PhD, of the Massachusetts General Hospital, reported the findings for the 777 CLP-29 Study Group at the 2006 ASCO meeting (abstract LBA525).
This multinational randomized, double-blind, double-dummy phase III clinical trial enrolled postmenopausal women with advanced breast cancer who were ER and/or PR positive. "The overwhelming majority of patients had not had adjuvant chemotherapy or adjuvant endocrine therapy," Dr. Goss said.
Subjects received either atamestane 500 mg/d with toremifene 60 mg/d (n = 434), or letrozole 2.5 mg/d (n = 431). The primary endpoint was TTP. The study had 80% power to detect a 25% increase in TTP and assumed a TTP of 9.4 months in the letrozole group.
"We considered the option of atamestane and toremifene against atamestane alone, as well as against toremifene alone, but in 2001 when this study was designed, letrozole had just been approved as first-line metastatic therapy. FDA did not favor toremifene or atamestane in the control arm but accepted this design as the best proof of concept of complete estrogen blockade against letrozole," he said.
The overall TTP for the study population was 11.2 months for both treatment groups. The objective response rate overall was 30% for the combination and 36% for letrozole alone. "The distribution of responses was fairly well balanced," Dr. Goss said. Time to progression, median time to treatment failure, and median survival were identical between the two arms, he concluded.