The U.S. Food and Drug Administration today approved a potentially groundbreaking new drug to treat women with advanced breast cancer, signaling a new treatment strategy to arrest tumor growth and extend the time before the cancer worsens.

The drug, IBRANCE (palbociclib) was studied in 165 post-menopausal breast cancer patients with advanced ER+, HER2- disease who had received no prior systemic therapy for their metastatic disease. Early results from a clinical study led by UCLA researchers showed a dramatic improvement and the FDA granted the drug "breakthrough therapy" status in April 2013, allowing it to be fast-tracked to early approval.

The ER+/HER2- subgroup represents the largest proportion of breast cancer cases and is traditionally treated with therapies, like tamoxifen or letrozole, that target the hormone receptor pathway.

"Palbociclib (IBRANCE) is the first drug in its class to be approved by the FDA," said Dr. Richard Finn, the study's principal investigator and a researcher at UCLA's Jonsson Comprehensive Cancer Center. "All of us at UCLA are very proud of the important role we played in bringing this new agent to patients."

Developed by Pfizer Inc., IBRANCE (palbociclib) targets a key family of proteins (CDK4/6) responsible for cell growth by preventing cells from dividing. Results of the multi-year phase 2 study showed a significant increase in progression-free survival (PFS) for patients with advanced breast cancer that was estrogen receptor positive (ER+), HER2-negative (HER2-), who were given 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," said Dr. Dennis Slamon, director of the Revlon/UCLA Women's Cancer Research Program and Clinical/Translational Research at the Jonsson Cancer Center. "I believe palbociclib will now become a standard treatment approach for postmenopausal women with ER+/HER2- metastatic breast cancer."

Developing IBRANCE: A New Hope in the Fight Against Breast Cancer

advertisement

The origin of the research began in 2007, when Finn and Slamon held a pivotal meeting with Pfizer to discuss palbociclib and other experimental drugs in its pipeline.

Preclinical work testing the drug 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 Finn and Slamon built on laboratory work directed at the Jonsson Cancer Center's Translational Oncology Research Laboratory at UCLA.

Once the phase 1 study was completed and showed the drug was safe, the phase 2 study was performed in 165 post-menopausal breast cancer patients with advanced ER+, HER2- disease who had not received prior systemic therapy for their metastatic disease.

Phase 2 results showed progression-free survival was essentially doubled to 20.2 months for patients who received palbociclib plus letrozole as compared to 10.2 months for those who received the current standard treatment of letrozole alone. The PFS results indicated a 51 percent reduction in the risk of disease progression with the addition of palbociclib to letrozole.

"What is really remarkable is that we doubled the median progression-free survival," said Finn. "That type of result is not often seen in cancer medicine."

Slamon added that, "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."

advertisement

The results showed that over 80 percent of the metastatic ER+ breast cancer patients in the study received some benefit from this treatment, said Finn and Slamon. They also found the drug's safety profile is distinct from traditional chemotherapy, but does result in a lowered white blood cell count, which was manageable.

A phase 3 international clinical trial of the drug conducted by Finn and Slamon with Pfizer in approximately 660 ER+, HER2- advanced breast cancer patients has been completely enrolled.

Survivor Stories: A Second Chance at Life

When Janet Klein was first diagnosed with stage I ER+ breast cancer, she decided to undergo a double mastectomy in 2004. A few years later, it was discovered that the breast cancer had returned as metastatic disease in her bones.

Klein's UCLA oncologist and Jonsson Cancer Center member Dr. Sara Hurvitz told her about a phase 1 clinical trial that was being offered to UCLA patients with advanced breast cancer in 2009.

Nine months after she enrolled in the trial and was prescribed IBRANCE (palbociclib) in combination with an anti-estrogen treatment, her scans showed no evidence of the cancer.

"I had a large party with a lot of champagne, it was life changing but in a good way," said Klein.

The 59-year-old cancer survivor is celebrating again, after the FDA approved the use of the drug.

"Sixty percent 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," she said.

Gloria Zollar joined the phase 2 clinical trial in August 2010, after her UCLA oncologist discovered that her advanced breast cancer had spread to her bones. She has been on treatment since that time, over four years.

But only one year later, doctors noticed that her tumors had stopped progressing, which allowed Zollar to remain active and continue playing golf.

"I am now in remission, and everyday I'm thankful to God that I'm alive and able to see my great-grandchildren and spend time with them," said Zollar. The 78-year-old patient is excited that the drug is now available to other women battling this deadly disease.

"I am very pleased that other women could have a second chance at life like many of us who participated in the trial," she said.