|Sensitive then, sensitive now|
|The cyclin-dependent kinase 4 and 6 (CDK4/6) promote tumor cell proliferation in hormone-receptor-positive breast cancer, in concert with estrogen-receptor signaling. In a randomized, phase 3 trial (PALOMA-2 trial), results indicated palbociclib (a CDK4/6 inhibitor) and letrozole (an aromatase inhibitor, which reduces the levels of estrogen) prolonged progression-free survival for those with estrogen-receptor-positive, HER2-negative breast cancer who had not been treated. Data of the PALOMA-3 trial showed that hormone-receptor-positive, HER2-negative breast cancer patients bearing relapsed or progressed disease who had received endocrine therapy had progression-free benefit upon the combined treatment of palbociclib and fulvestrant (a selective estrogen receptor degrader) compared those treated with placebo and fulvestrant. However, whether the combination of CDK4/6 inhibitors and hormone therapy could prolong overall survival of recurrent/progressed hormone-receptor-positive, HER2- negative breast cancer patients that have been previously treated by endocrine therapy remains unclear.
The team led by Dr. Turner and colleagues published the results in a recent issue of the New England Journal of Medicine (here). A total of 521 patients—347 individuals in the palbociclib-fulvestrant group and 174 participants in the placebo-fulvestrant group—were enrolled in this double-blind randomized trial. After a median follow-up of 44.8 months, the median overall survival was 34.9 months in the palbociclib-fulvestrant group, and 28.0 months in the placebo-fulvestrant group, yielding no statistical difference between groups. However, in the subgroup analyses for those who were sensitive to previous endocrine therapy, the median overall survival was 39.7 months in the palbociclib-fulvestrant group, whereas the median overall survival was 29.7 months in the placebo-fulvestrant group, indicating overall survival benefit in this subgroup treated by palbociclib and fulvestrant. The rates of adverse events, most of which were hematologic, were comparable between groups.
Data of the PALMOA-3 trial indicate the combination of palbociclib and letrozole improve overall survival in recurrent or progressed hormone-receptor-positive, HER2-negative breast cancer patients that were previously sensitive to endocrine therapy.
This trial was supported by a pharmaceutical company.