Palbociclib (Ibrance®) is an oral, reversible, selective, small molecule inhibitor of cyclin-dependent kinase (CDK) 4 and CDK6, developed by Pfizer for the treatment of cancer. CDKs are important regulators of cell cycle entry and progression in response to growth signals, and inhibition of these kinases with palbociclib may enhance the activity of other anticancer drugs in tolerated regimens.

Faslodex(Fulvestrant): Treatment Effect, Symptom Relief, Clinical Outcome

Palbociclib was recently approved in combination with letrozole in the United States for first-line treatment of advanced breast cancer. Phase III development is ongoing worldwide, investigating it as first-line treatment of advanced breast cancer, as well as for the treatment of recurrent or advanced breast cancer and high-risk early breast cancer.

Palbociclib, an inhibitor of cyclin-dependent kinases 4 and 6 (CDK4/6), combined with Fulvestrant prolonged progression-free survival in patients with hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer.

Trial content

Randomly assigned patients with hormone receptor-positive, HER2-negative advanced breast cancer who had progressed or relapsed on prior endocrine therapy to receive palbociclib plus Fulvestrant or placebo plus Fulvestrant. Overall survival was analyzed; the efficacy of palbociclib, the efficacy of subsequent treatment after disease progression, and safety were evaluated according to prespecified stratification factors such as the presence or absence of sensitivity to endocrine therapy, the presence or absence of visceral metastatic disease, and menopausal status.

Trial results

Among the 521 patients who underwent randomization, the median overall survival was 34.9 months in the palbociclib-Fulvestrant group and 28.0 months in the placebo-Fulvestrant group.

Trial 2 content

Among the 410 patients who were sensitive to prior endocrine therapy, the median overall survival was 39.7 months in the palbociclib-Fulvestrant group and 29.7 months in the placebo-Fulvestrant group. The median duration of subsequent treatment was similar in the two groups, with the palbociclib-Fulvestrant group receiving chemotherapy for a median of 17.6 months and the placebo-Fulvestrant group for 8.8 months. No new safety signals were observed after 44.8 months of follow-up.

Trial results

In patients with hormone receptor-positive, HER2-negative advanced breast cancer who were sensitive to previous endocrine therapy, palbociclib-Fulvestrant prolonged overall survival compared with placebo-Fulvestrant. There was no significant difference in overall survival across the trial groups. Overall survival depends on the patient's sensitivity to previous endocrine therapy.