The combination of Femara® (letrozole) and the investigational agent PD 0332991 significantly improved median progression-free survival in patients with advanced estrogen receptor-positive (ER-positive) breast cancer, according to the results of a study presented at the 2012 CTRC-AACR San Antonio Breast Cancer Symposium.

Each year roughly 200,000 U.S. women are diagnosed with breast cancer. Many of these breast cancers are ER-positive, meaning that they are stimulated to grow by the female hormone estrogen. Treatment of ER-positive breast cancer often involves hormonal therapies that suppress or block the action of estrogen.

Femara is a type of hormone therapy known as an aromatase inhibitor and works by suppressing the production of estrogen in postmenopausal women. PD 0332991 is an investigational, oral, targeted agent that inhibits cyclin-dependent kinase (CDK) 4/6. Some research has shown that CDK 4/6 inhibition may play a role in the treatment of some breast cancers.

Researchers conducted a two-part, phase II study to evaluate PD 0332991 in combination with Femara. Part one included 66 postmenopausal women with ER-positive, HER2-negative metastatic breast cancer. Part two included 99 postemenopausal women with ER-positive, HER2-negative metastatic breast cancers with certain genomic alterations, specifically cyclin D1 (CCND1) amplification and/or p16 loss. In both parts of the study, women were randomized to receive Femara plus PD 0332991 or Femara alone. Treatment continued until disease progression, unacceptable toxicity, or withdrawal.

The results indicated that women in the combination treatment arm experienced a progression-free survival of 26.1 months, compared to 7.5 months for those treated with Femara alone. The combination treatment produced a 45 percent response rate, compared to 31 percent for Femara alone. The clinical benefit rate was 70 percent with the combination treatment and 44 percent with Femara alone. The combination treatment was well tolerated. The most common adverse events were neutropenia, leukopenia, anemia and fatigue.

Retrospective analysis of the biomarkers for CCND1 amplification or p16 loss indicated that the only biomarker necessary to select patients who were most likely to benefit from PD 0332991 was ER-positive status.

Research will be ongoing to evaluate PD 0332991 for the treatment of metastatic ER-positive breast cancer. If phase III studies verify these findings, PD 0332991 could become an important new treatment option for this patient population.


Finn RS, Crown JP, Lang I, et al. Results of a randomized phase 2 study of PD 0332991, a cyclin-dependent kinase (CDK) 4/6 inhibitor, in combination with letrozole vs letrozole alone for first-line treatment of ER+/HER2- advanced breast cancer (BC). Presented at the 2012 CTRC-AACR San Antonio Breast Cancer Symposium. December 4-8, 2012. Abstract S1-6.

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