Pfizer has announced that the randomized Phase 2 trial, PALOMA-1, of Palbociclib achieved its primary endpoint by demonstrating a statistically significant and clinically meaningful improvement in progression-free survival ( PFS ) for the combination of Palbociclib and Letrozole ( Femara ) compared with Letrozole alone in post-menopausal women with estrogen receptor positive ( ER+ ), human epidermal growth factor receptor 2 negative ( HER2- ) locally advanced or newly diagnosed metastatic breast cancer.
ER+ and HER2- advanced breast cancer represents approximately 60% of the advanced breast cancer population.
Adverse events observed for the Palbociclib arm were consistent with the known adverse event profile for this combination. Detailed efficacy and safety data from PALOMA-1 will be submitted for presentation at the American Association for Cancer Research ( AACR ) Annual Meeting 2014.
Palbociclib has received Breakthrough Therapy designation by the United States Food and Drug Administration ( FDA ) in April 2013, for the initial treatment of women with advanced or metastatic ER+, HER2- breast cancer.
This designation was based on interim data from the PALOMA-1 trial.
Palbociclib is an investigational oral targeted agent that selectively inhibits cyclin-dependent kinases ( CDKs ) 4 and 6 to regain cell cycle control and block tumor cell proliferation. Loss of cell cycle control is a hallmark of cancer and CDK 4/6 are overactivated in numerous cancers, leading to loss of proliferative control.
CDK 4/6 are key regulators of the cell cycle that trigger cellular progression from growth phase ( G1 ) into phases associated with DNA replication ( S ).
CDK 4/6, whose increased activity is frequent in estrogen receptor-positive ( ER+ ) breast cancer, are key downstream targets of ER signaling in ER+ breast cancer.
Preclinical data suggest that dual inhibition of CDK 4/6 and ER signaling is synergistic and has been shown to stop growth of ER+ breast cancer cell lines in the G1 phase.
PALOMA-1 ( also known as Study 1003 ) is a Phase 2 trial designed to assess the progression-free survival of Palbociclib ( 125 mg once daily for three out of four weeks in repeated cycles ) in combination with Letrozole versus Letrozole alone ( 2.5 mg once daily on a continuous regimen ) in post-menopausal women with ER+, HER2- advanced breast cancer.
Progression-free survival is comprised of time from randomization to time of disease progression or death from any cause. PALOMA-1 is a multi-center trial with 101 global sites participating.
Pfizer has initiated two Phase 3 studies of Palbociclib in advanced/metastatic breast cancer. PALOMA-2 ( also known as Study 1008 ) is a randomized ( 2:1 ), multi-center, double blind study that evaluates Palbociclib in combination with Letrozole versus Letrozole plus placebo as first-line treatment for post-menopausal patients with ER+, HER2- advanced breast cancer.
PALOMA-3 ( also known as Study 1023 ) is a randomized ( 2:1 ), multi-center, double blind 3 study that evaluates Palbociclib in combination with Fulvestrant versus Fulvestrant plus placebo in women with hormone receptor-positive ( HR+ ), HER2- metastatic breast cancer whose disease has progressed after prior endocrine therapy.
Source: Pfizer, 2014