Breakthrough Breast Cancer Treatment Granted FDA Priority Review

The FDA today granted priority review status to a breakthrough breast cancer drug developed by Pfizer Inc.

Combined with letrozole, palbociclib is a treatment for postmenopausal women with estrogen receptor positive (ER+) and human epidermal growth factor receptor 2 negative (HER2-) advanced breast cancer who have not previously undergone systemic treatment for the disease. The first-line treatment was granted breakthrough therapy designation by the FDA in April 2013.

“If approved as a first-line therapy in combination with letrozole, palbociclib will be an important new option for the thousands of women in the United States who are living with metastatic breast cancer,” said Pfizer Oncology President Garry Nicholson in a press release. “We look forward to continuing to work closely with the FDA through the review process.”

Palbociclib is an oral agent that inhibits cyclin-dependent kinases (CDKs) 4 and 6 in order to regain cell cycle control and block the proliferation of tumor cells. Increased activity by CDK 4/6 is frequent in ER+ breast cancer.

CDK 4/6 are regulators of cell cycles that trigger cellular progression from the growth phase into phases associated with DNA replication. CDK 4/6 have also been found to become overactivated in numerous cancers, which leads to the loss of proliferative control. Preclinical data suggests inhibiting both CDK 4 and 6 can stop the growth of ER+ BC cell lines in the G1 phase.

Pfizer has initiated multiple phase 3 clinical trials to evaluate palbociclib for the treatment of advanced and metastatic breast cancer. One of the trials is a randomized multi-center, double blind study to evaluate palbociclib in combination with letrozole, compared with letrozole plus placebo, as a first-line treatment for postmenopausal patients with ER+, HER2- advanced breast cancer.

Another is a randomized multi-center, double blind trial to evaluate 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.

Both trials recently completed patient enrollment.

Investigators are also enrolling patients to study palbociclib for advanced/metastatic breast cancer and early breast cancer. A randomized, multi-center, open-label trial will evaluate palbociclib in combination with exemestane compared with capecitabine in postmenopausal women with ER+, HER2- metastatic breast cancer whose disease was refractory to previous nonsteroidal aromatase inhibitors (letrozole or anastrozole).

An additional randomized, double blind, placebo-controlled study compares palbociclib with standard endocrine therapy versus placebo plus standard endocrine therapy in patients with HR+, HER2- early-stage breast cancer with certain features that suggest an increased risk for recurrence after preoperative chemotherapy followed by surgery.

The FDA is expected to decide on the treatment’s approval on April 13, 2015.