Pfizer announced that it intends to file a New Drug Application (NDA) with the U.S. Food and Drug Administration (FDA) for palbociclib in combination with letrozole as first-line systemic treatment of post-menopausal women with estrogen receptor positive (ER+), human epidermal growth factor receptor 2 negative (HER2-) locally advanced or metastatic breast cancer.
The intended filing was supported by the company’s discussions with the FDA and supported by the final results of the randomized Phase II PALOMA-1 trial investigating progression-free survival in patients who received palbociclib in combination with letrozole compared to letrozole alone. The FDA awarded palbociclib Breakthrough Therapy designation based on positive results from the trial.
Breast cancer is the leading cancer in women around the world. According to the World Health Organization, breast cancer incidence is rising in the developing world due to increased life expectancy, growing urbanization, and adoption of western lifestyles. Early detection is key to improve breast cancer outcomes as breast cancer is often diagnosed in its late stages, especially in low- and middle- income countries.
Palbociclib is an investigational oral targeted agent that performs selective inhibition on cyclin-dependent kinases (CDKs) 4 and 6 in order to regain cell cycle control and stop tumor cell growth. Preclinical data suggests that dual inhibition of CDK 4/6 and estrogen receptor-positive signaling is synergistic and influential in stopping proliferation of ER + BC lines in the growth 1 (G1) phase.
The company has started two Phase III studies of the drug in advanced or metastatic breast cancer, PALOMA-2 and PALOMA-3. PALOMA-2 extends the investigation of the combination treatment albociclib in combination with letrozole versus letrozole plus placebo as a first-line treatment for post-menopausal patients with ER+, HER2- advanced breast cancer. PALOMA-3 evaluates palbociclib in combination with fulvestrant compared to fulvestrant with placebo in women with hormone receptor-positive (HR+), HER2- metastatic breast cancer who went through endocrine therapy but who experienced disease progression.
Pfizer said it anticipates filing the NDA based on the PALOMA study results early in the third quarter of 2014.