On February 3, the Food and Drug Administration (FDA) approved a new drug that has showed promising results for women with aggressive estrogen receptor positive (ER+) breast cancer. The new drug, IBRANCE (palbociclib), provides a new treatment strategy to halt tumor growth and extend the time before the cancer worsens. The approval was made after the release of the results of a study led by researchers at UCLA’s Jonsson Comprehensive Cancer Center.
The cancer drug developed by Pfizer, Inc., IBRANCE, was evaluated in 165 post-menopausal breast cancer patients who had with advanced ER+, human epidermal growth factor receptor 2 negative (HER2–) cancers who had received no prior systemic (whole body) treatment for their metastatic disease (cancer that had spread beyond the breast). Early results from the multi-year clinical study found a significant improvement; therefore, the granted the drug “breakthrough therapy” status in April 2013, allowing it to be fast-tracked to early approval.
“Palbociclib is the first drug in its class to be approved by the FDA,” explained principal investigatorRichard Finn, a researcher at UCLA’s Jonsson Comprehensive Cancer Center. He added, “All of us at UCLA are very proud of the important role we played in bringing this new agent to patients.” He explained that the ER+/HER2- subgroup represents the largest proportion of breast cancer cases and is traditionally treated with treatments such as tamoxifen or letrozole, which target the hormone receptor pathway.
IBRANCE targets an important family of proteins (CDK4/6), which are responsible for cell growth by preventing cells from dividing. Results of the study showed a significant increase in progression-freesurvival (PFS) for women with advanced breast cancer that was estrogen receptor positive ER+, HER2– who received a combination of a standard anti-estrogen treatment, letrozole, and palbociclib compared to letrozole alone.
“With the FDA approval, this study represents a potential practice-changing result,” explained Dennis Slamon, PhD, director of the Revlon/UCLA Women’s Cancer Research Program and Clinical/Translational Research at the Jonsson Cancer Center. He added, “I believe palbociclib will now become a standard treatment approach for postmenopausal women with ER+/HER2- metastatic breast cancer.”
The research began in 2007, when Drs. Finn and Slamon held a key meeting with Pfizer to discuss palbociclib and other experimental drugs under development by the company. Preclinical studies tested the drug in a tissue culture of human breast cancer cells extremely encouraging activity, specifically against ER+ cancer cells. This finding led to a clinical study alliance with Pfizer led by Drs. Finn and Slamon based on laboratory studies at the Jonsson Cancer Center’s Translational Oncology Research Laboratory at UCLA. After drug safety was established by a he phase 1 study, phase 2 study was conducted on the 165 post-menopausal breast cancer patients with advanced ER+, HER2- cancers. The results of this study showed that progression-free survival was essentially doubled to 20.2 months for the women who received IBRANCE plus letrozole, compared to 10.2 months for those who received the standard treatment of letrozole alone. The women who received IBRANCE experienced a 51% reduction in the risk of disease progression.
Dr. Finn explained, “What is really remarkable is that we doubled the median progression-free survival. That type of result is not often seen in cancer medicine.” Dr. Slamon added, “The magnitude of the observed benefit was very gratifying and reminiscent of results we saw when we conducted the initial studies on Herceptin in HER2+ breast cancers two decades ago.” Drs. Finn and Slamon explained that the results showed that more than 80% of the metastatic ER+ breast cancer patients in the study received some benefit from this treatment. They also found that the drug’s safety profile is distinct from traditional chemotherapy; however, it does result in a lowered white blood cell count, which was manageable. Moving forward, a phase 3 international clinical trial of the drug conducted by the two doctors and Pfizer comprised of approximately 660 ER+, HER2- advanced breast cancer patients has been completely enrolled.
In 2004, Janet Klein was diagnosed with stage I ER+ breast cancer and decided to undergo a double mastectomy. A few years later, the cancer returned as metastatic disease in her bones. Her UCLA oncologist and Jonsson Cancer Center member Dr. Sara Hurvitz told her about the phase 1 clinical trial that was being offered to UCLA patients with advanced breast cancer in 2009. Nine months after Janet enrolled in the study and was prescribed IBRANCE in combination with an anti-estrogen treatment, her scans showed no evidence of the cancer. She said, “I had a large party with a lot of champagne, it was life changing but in a good way.” The 59-year-old cancer survivor is celebrating again, after the drug received FDA approval. She said, “60% of all women diagnosed with this disease have my variety, and this drug having this sort of an impact, so fast and so effectively, is earth shattering.”
In August 2010, Gloria Zollar enrolled in the phase 2 clinical trial, after her UCLA oncologist discovered that her advanced breast cancer had spread to her bones. She has been on treatment since that time, for more than four years. However, only one year after enrolling in the study, her physicians discovered that her tumors had stopped progressing, which allowed her to remain active and continue playing golf. The 78-year-old woman explained, “I am now in remission, and every day I’m thankful to God that I’m alive and able to see my great-grandchildren and spend time with them.” She is excited that the drug is now available to other women battling this deadly disease. She explained, “I am very pleased that other women could have a second chance at life like many of us who participated in the trial.”
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