RWD Show Survival Advantage of Frontline Letrozole Plus Palbociclib in Minorities With aBC

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 codirector of the Comprehensive Breast Cancer Center, discusses the real-world efficacy of letrozole (Femara) in combination with palbociclib (Ibrance) as treatment of patients with estrogen receptor-positive, HER2-negative, advanced breast cancer, based on race and ethnicity.

Patients with ER-positive, HER2-negative, advanced breast cancer were evaluated on this treatment in the phase 3 PALOMA-2 study (NCT01740427), explained Brufksy. Overall, there was no survival benefit shown in the overall study population when palbociclib was added to letrozole. However, a progression-free and overall survival was shown in patients who identified as Black or Hispanic.

0:07 | Obviously, real-world analyses can’t replace randomized clinical trials. But it can add a lot of data to it. Randomized clinical trials, as much as we love them, especially since the NSAB over the last 50 years has really changed the practice of breast oncology, only refer to the patients in the trial. And the patients had to be very restrictive. In their entry criteria, the treatment is very restricted, you can’t violate or have the lab values be abnormal for more than a couple of weeks. I think people have tried a lot of times.

0:41 | Another thing is that these trials take so long to conduct in breast cancer, because people rightfully live such a long time, that the standard-of-care for the placebo arm changes. So, you have all these issues. For that reason, I think a lot of us have gotten very interested in real-world analyses. I think the 21st Century Cures Act from the FDA, that was an act of that, again, I think, within the last 5 years or so, really allows for the use of real-world evidence that is from databases, or charter reviews, or things like that to be at least considered in drug approvals, or label expansions. It doesn't replace a randomized clinical trial. I think it fills in the data, in particular groups that maybe were under-represented in the trial like elderly or various minority groups, African Americans, for example. I think that looking at those subgroups in the real-world analysis helps us out.

1:32 | We did a real-world analysis of first-line palbociclib and letrozole from the Flatiron database, which is a large database of about 2.8 million records. When we did this analysis, a bunch of investigators got together with Pfizer, and we analyze looks at me and I was about 1,300 or 1,400 patients per, or even higher who receive letrozole only, starting in 2015 and going up to 2020, or letrozole with palbociclib. And we did a variety of physical techniques to try to eliminate confounding and bias to the best we could do. There's always going to be confounding and bias, but we use things like inverse probability treatment waiting, and propensity score matching to try to match them as closely as we could. When we did that, we found not only a progression-free survival benefit that was very similar to that seen in PALOMA-2, but there was an overall survival benefit that was totally significant. So even though the randomized trial didn't show any benefit in terms of overall survival with Palbociclib, the real data did. And so, this kind of consistent with the idea that there probably are going to be differences between the 3 CDK4/6 inhibitors, and the issue is how clinically significant those differences are. And I think that's still a matter of open debate amongst breast oncologists.