Promising drug doubles positive effect in hormone-receptor–positive breast cancer

Breast cancer researchers from the Revlon / UCLA Women's Cancer Research Program at UCLA's Jonsson Comprehensive Cancer Center announced final clinical trial results this week that showed the amount of time patients were on treatment without their cancer worsening (called "progression-free survival") was effectively doubled in women with advanced breast cancer who took the experimental drug palbociclib.

The results of the phase 2 clinical trial were announced at the American Association for Cancer Research annual meeting in San Diego.

Palbociclib (PD 0332991) is an investigational drug discovered and being developed by Pfizer Inc.

The preclinical work testing palbociclib in a panel of human breast cancer cells growing in culture dishes showed very encouraging activity, specifically against estrogen-receptor–positive (ER+) cancer cells.

This led to a clinical study collaboration with Pfizer led by Dr. Richard Finn, associate professor of medicine at the Jonsson Cancer Center. The phase 1 study built on laboratory work from the Translational Oncology Research Laboratory, which is directed by Dr. Dennis Slamon, professor of medicine at the Jonsson Cancer Center and director of the Revlon/UCLA Women's Cancer Research Program.

The preclinical observations were moved into a phase 1 clinical study led by Finn and Slamon at UCLA. The study was designed to determine the doses and initial safety results of combining palbociclib with letrozole, a commonly used drug for advanced ER+ breast cancer. Once the phase 1 study was completed, the phase 2 study was performed in 165 postmenopausal breast cancer patients with advanced ER+, HER2- disease.

"By combining the test drug, palbociclib, with the standard drug, letrozole, we demonstrated a dramatic and clinically meaningful effect on progression-free survival in women with ER+ advanced breast cancer," Finn said. "We are gratified and excited that these results confirm the preclinical work we began at the Translational Laboratory."

As the primary endpoint of the study, progression-free survival was 20.2 months for patients who received palbociclib plus letrozole, and 10.2 months for those who received letrozole only. The progression-free survival results indicated a 51 percent reduction in the risk of disease progression with the addition of palbociclib to letrozole.

"Our final results very much validate the Translational Laboratory approach," Slamon said. "By identifying the effective treatment targets in the correct patients, we advance personalized cancer treatment that we hope will greatly improve outcomes for this group of women with breast cancer. These results are as exciting as the initial results we saw for trastuzumab (Herceptin) in HER2+ breast cancers but represent a new approach for women with advanced ER+ breast cancer. This group is different from the women with HER2+ breast cancer, and comprises approximately 60 per cent of all advanced breast cancer patients, compared with 20 percent with HER2+ cancer."