An experimental drug known as palbociclib, developed by Pfizer, Inc. and tested at the Revlon/UCLA Women’s Cancer Research Program in UCLA’s Jonsson Comprehensive Cancer Center (JCCC), extended progression-free survival of women with breast cancer by twice that achieved in women treated without palbociclib in a phase 2 clinical trial. The news was presented at the American Association for Cancer Research Annual Meeting held in San Diego.
“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,” said Dr. Richard S. Finn, associate professor of medicine at JCCC, in a news release from UCLA. “We are gratified and excited that these results confirm the preclinical work we began at the Translational Lab.”
Pfizer developed palbociclib (PD 0332991) in preclinical work using a panel of human breast cancer cells. Notably, the drug was especially effective against estrogen receptor positive (ER+) breast cancer cells. Additionally, Dr. Dennis Slamon, professor of medicine at JCCC and director of the Revlon/UCLA Women’s Cancer Program, conducted research in his lab at the Translational Oncology Research Laboratory. These preclinical investigations led to a phase 1 clinical trial with collaborations between JCCC and Pfizer and led by Dr. Finn.
During this study, which was based in UCLA, Drs. Finn and Slamon established a dosing regimen and safety profile for the use of palbociclib with letrozole. After these were developed, the two doctors initiated the phase 2 trial in 165 post-menopausal women with advanced ER+, HER2- breast cancer.
“Our final results very much validate the Translational Laboratory approach,” said Dr. Slamon. “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.”
Final results, published in “The Cyclin-dependent Kinase 4/6 Inhibitor Palbociclib in Combination with Letrozole Versus Letrozole Alone As First-line Treatment of Oestrogen Receptor-positive, HER2-negative, Advanced Breast Cancer (PALOMA-1/TRIO-18): a Randomised Phase 2 Study” identified a 20.2-month progression-free survival for patients treated with both palbociclib and letrozole, compared to a 10.2-month progression-free survival for patients treated with letrozole alone. This represented a 51% reduction in the risk for disease progression.
“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 ER+ advanced breast cancer,” stated Dr. Slamon. “This group is different from HER2+ breast cancer and affects approximately 60 percent of all advanced breast cancer patients compared with approximately 20 percent for HER2.” If palbociclib passes into phase 3 trials and into the clinic, it may have a significant impact on the way ER+ breast cancer patients are treated.