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Breast Cancer Drug Receives Breakthrough Designation from FDA
Posted Date: 4/11/2013 12:00 PM
Faculty: Dennis Slamon, M.D., Ph.D., Richard Finn, M.D.

Dr. Dennis Slamon

Richard Finn, M.D.

Dr. Dennis Slamon

Dr. Richard Finn

An experimental drug investigated for the treatment of advanced breast cancer by researchers from the Revlon/UCLA Women’s Cancer Research Program at UCLA’s Jonsson Comprehensive Cancer Center (JCCC) today received “Breakthrough Therapy” designation by the United States Food and Drug Administration (FDA).

Palbociclib (PD 0332991, Pfizer, Inc.) has shown a significant increase in progression-free survival (PFS, the length of time a patient is on treatment without tumor growth) for patients with advanced breast cancer that was estrogen receptor positive (ER+), HER2-negative (HER2-) and who were given a combination of the standard anti-estrogen treatment letrozole and palbociclib compared to letrozole alone.
The phase 2 clinical data supporting the designation were initially reported in December 2012 at the CTRC-AACR San Antonio Breast Cancer Symposium by Dr. Richard S. Finn, associate professor of medicine at JCCC. The clinical study was built on laboratory work from the Translational Oncology Research Laboratory directed by Dr. Dennis Slamon, Professor of Medicine at JCCC and director of the Revlon/UCLA Women’s Cancer Research Program.
The preclinical work testing palbociclib in a panel of human breast cancer cells growing in culture dishes showed very encouraging activity, specifically against ER+ cancer cells. These preclinical observations were then moved into phase 1 clinical studies led by Finn and Slamon at UCLA. Those studies were designed to determine the doses and initial safety results of a combination with letrozole, a commonly used drug for ER+ breast cancer.

Once the phase 1 studies were completed, the phase 2 studies were performed in 165 breast cancer patients with ER+ disease. The “Breakthrough Therapy” designation was based on the preliminary analysis of the phase 2 data showing that the median PFS of patients given the palbociclib-letrozole combination was 26.1 months compared to 7.5 months for those given letrozole alone. Among patients with measurable disease, 45 percent receiving the combination had confirmed responses, compared to 31 percent with letrozole alone, and the clinical benefit rates (tumor shrinkage and/or stable disease for a minimum of six months) were 70 and 44 percent, respectively.

Enacted as part of the 2012 FDA Safety and Innovation Act (FDASIA), Breakthrough Therapy designation is intended to expedite the development and review of a potential new medicine if it is “intended, alone or in combination with one or more other drugs, to treat a serious of life-threatening disease or condition and preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints.”

“This drug combination demonstrated a dramatic and clinically meaningful effect on PFS in women with ER+ breast cancer,” said Finn. “These results confirm the preclinical work we began at the Translational Lab.”

Finn and colleagues have initiated a randomized, multicenter, double-blind phase 3 study to evaluate palbociclib combined with letrozole compared to letrozole alone as a first-line treatment for post-menopausal patients with ER+, HER2-, locally advanced or metastatic breast cancer. The researchers will continue to work closely with Pfizer and the FDA to better understand the implications of Breakthrough Therapy designation with the hope that further study will support potential regulatory submission.

“The results of this phase 2 study validate the Translational Laboratory approach by identifying the correct targets for treatment in the right patient population," said Slamon. "We move forward with personalized oncology that we hope will greatly improve the outcomes for this group of breast cancer patients. These results are as exciting as the initial results we saw for trastuzumab (Herceptin) in HER2+ breast cancers but represent a new approach for a different and larger subset of breast cancers, i.e., those that are ER+. We are working diligently to enroll the phase 3 validation study as quickly and safely as possible.”

UCLA's Jonsson Comprehensive Cancer Center has more than 240 researchers and clinicians engaged in disease research, prevention, detection, control, treatment and education. One of the nation's largest comprehensive cancer centers, the Jonsson center is dedicated to promoting research and translating basic science into leading-edge clinical studies. In July 2012, the Jonsson Cancer Center was once again named among the nation’s top 10 cancer centers by U.S. News & World Report, a ranking it has held for 12 of the last 13 years. For more information on the Jonsson Cancer Center, visit our website at http://www.cancer.ucla.edu.



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