Brufsky Discusses Background on Palbociclib in Breast Cancer

Adam Brufsky, MD, PhD, FACP, professor of medicine at the University of Pittsburgh School of Medicine, associate division chief for the Division of Hematology/Oncology at the University of Pittsburgh School of Medicine's Department of Medicine, medical director of the Magee-Women's Cancer Program, associate director for clinical investigations at UPMC Hillman Cancer Center, and co director of the Comprehensive Breast Cancer Center, discusses background and previous clinical data on palbociclib (Ibrance) as a treatment option for patients with estrogen receptor (ER)-positive, HER2-negative, advanced breast cancer.

Palbociclib is a first-in-class CDK4/6 inhibitor. Currently, the agent is approved for use in combination with an aromatase inhibitor or fulvestrant in patients with hormone receptor-positive, HER2-negative advanced breast cancer.

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0:08 | Palbociclib was the first CDK4/6 inhibitor on the market, and so we have the most data for it. There were a variety trials, the most important 1 was a trial called PALOMA-2 [NCT01740427], which was a randomized trial, I think of about 660 patients who had first-line, so they were untreated for the metastatic setting, estrogen receptor-positive metastatic breast cancer. They were given either letrozole [Femara] 2.5 mg a day, or letrozole and palbociclib

0:46 | The progression-free survival, which has been updated multiple times, shows a hazard ratio of about .58 absolute benefit for about 14 to 15 months to about 27-28 months. It's almost doubling progression-free survival. I think the important part though was that data was updated recently, within the last year at ASCO, and what was shown in the overall survival, the trials were not powered for overall survival, that was the issue, so the overall survival was equivalent. It was about 53 or 54 months in both arms, letrozole only, as well as the letrozole and palbociclib arm. That generated a lot of discussion because other CDK4/6 inhibitors, in particular ribociclib [Kisqali], appeared to have an overall survival benefit and abemaciclib [Verzenio], which was also presented recently, had a non-significant benefit that looked like about a year of absolute progression-free survival at the hazard ratio that is about .75.

1:52 | The issue is why did palbociclib not have that? I think it's a matter of some debate. One idea that's been floated is that in palbociclib in PALOMA-2, we didn't quite understand that you couldn't give letrozole after letrozole. There's a number of patients who just simply received an AI and palbociclib natural progression on an AI within 12 months of completing their adjuvant therapy in about 25% of the patients, 22% to 25%, in PALOMA-2 actually were patients who had progressed within 12 months of completion of their adjuvant therapy. This was a higher risk population. When you take those patients out and censored them, they have an overall survival that's similar to the other two CDK4/6 inhibitors.