In a groundbreaking study that offers new hope for women with advanced breast cancer, researchers from UCLA's Jonsson Comprehensive Cancer Center have published final clinical trial results 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.
An investigational drug discovered and being developed by Pfizer Inc., palbociclib targets a key family of proteins (CDK4/6) responsible for cell growth by preventing them from dividing. Results of the multi-year phase 2 study showed a significant increase in PFS for patients with advanced breast cancer that was estrogen receptor positive (ER+), HER2-negative (HER2-), who were given a combination of the standard anti-estrogen treatment, letrozole, and palbociclib compared to letrozole alone.
"We're essentially putting the brakes on cell proliferation and causing these tumor cells to stop growing," said Dr. Richard Finn, associate professor of medicine at UCLA and lead author of the study.
The study was published today online ahead of print in the journal The Lancet Oncology.
Unlocking the Power of Palbociclib
The origin of the research began in 2007, when Finn and cancer pioneer Dr. Dennis Slamon, UCLA professor of medicine and director of the Revlon/UCLA Women's Cancer Research Program, 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 clinical study collaboration with Pfizer led by Finn and built on laboratory work directed by Slamon at the Translational Oncology Research Laboratory at UCLA.
"When we studied palbociclib, we found that signal (CDK4/6) inhibition in breast cancer hadn't been seen before, or had been looked at but missed," said Slamon."That's what really got us on the track."
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.
Phase 2 results showed 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 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. "With the addition of palbociclib, PFS effectively doubled. That type of result is not often seen in cancer medicine."
Results found that over 80% of the metastatic ER+ breast cancer patients in the study received some benefit from this treatment, said Finn and Slamon. The drug doesn't have side effects like traditional chemotherapy, such as infections, but does result in a lowered white blood cell count, which was very manageable.
A phase 3 international clinical trial of the drug conducted by Finn and Slamon with Pfizer in 660 ER+, HER2- advanced breast cancer patients is ongoing.
Because so many of the patients in the early testing showed significant long-lasting responses, the FDA granted palbociclib "breakthrough therapy" status in late 2013.
Patient Given Second Chance at Life
Gloria Zollar, 78, mother of five, 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.
With FDA having granted palbociclib "Breakthrough" Therapy status in late 2013, Zollar hopes the drug is made available to other patients 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."
UCLA's Jonsson Comprehensive Cancer Center