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Lead PALOMA-2 Author Says Results Will Boost Global Use of Palbociclib

Laura Panjwani
Published: Monday, Nov 28, 2016

Richard Finn, MD

Richard Finn, MD

Results from the phase III PALOMA-2 study—which demonstrated a significant progression-free survival (PFS) advantage with palbociclib (Ibrance) plus letrozole compared with letrozole alone in ER-positive, HER2-negative metastatic breast cancer—were recently published in The New England Journal of Medicine.

The use of palbociclib, the first CDK4/6 inhibitor approved in this setting, will only continue to rise following these published findings, said lead study author Richard Finn, MD, an associate professor of Medicine at the UCLA David Geffen School of Medicine.

“The uptake has been very brisk in the United States, and that is really driven by the compelling efficacy data and the fact that it is well tolerated,” he said. “PALOMA-2 will just continue to boost that, not only in the United States, but globally.”

The double-blind, placebo-controlled trial found that the addition of the CDK4/6 inhibitor increased median PFS from 14.5 months to 24.8 months versus letrozole alone. The treatment was also well tolerated.

These findings confirm the results of the phase II PALOMA-1 study, which led to the February 2015 FDA accelerated approval of palbociclib as a frontline treatment for postmenopausal women with ER-positive, HER2-negative metastatic breast cancer.

In an interview with OncLive, Finn discussed the clinical impact of PALOMA-2 and palbociclib in ER-positive breast cancer and the reason CDK4/6 inhibition is effective in this patient population.

OncLive: What led to the development of palbociclib?

Finn: The development of palbociclib goes back several years. It was a drug that was really looking for an indication and there was a collaboration between myself, Dr Dennis Slamon, and others at UCLA Jonsson Comprehensive Cancer Center and Pfizer. We received this compound—which didn’t have a name at the time, it was called PD-0332991—and we did a preclinical evaluation to try and identify an indication for this CDK4/6 inhibitor. The biology of CDK4/6 had been around for a long time, but no one really had a good CDK4/6 inhibitor, and the companies that did were still looking for an indication of where to develop them.

In the preclinical findings, which were published in 2009 and referenced in The New England Journal of Medicine article, we identified that the ER-positive subtype of breast cancer is very sensitive to inhibition in the lab and that there was synergy between CDK4/6 inhibition with palbociclib and antiestrogens.

The phase II study, PALOMA-1, looked at 165 patients who received palbociclib and letrozole versus letrozole alone to see if the laboratory data held up in the clinic. That study was impressive. We saw a more than 10-month improvement in PFS, and it turned out to be very well tolerated. This was the basis for an accelerated approval by the FDA in 2015. There was always a commitment to do a real phase III registration study—not only for the FDA—but because several global registration authorities would not accept a phase II study.

How did PALOMA-2 compare with previous findings?

PALOMA-2 was a large phase III study, which had over 600 patients and was blinded and placebo-controlled with palbociclib and letrozole versus placebo and letrozole. The goal of the study was to serve as confirmation of PALOMA-1. Remarkably, the results were exactly like the phase II study. We went from a small, open-label phase II trial to a large randomized phase III trial, and we still saw the same increase of over 10 months improved PFS. The safety profile was also very much the same, as fewer than 2% of patients had neutropenic fever and it was very well tolerated.

What impact has palbociclib had for patients with ER-positive breast cancer?

There has been a lot of effort to improve on single-agent endocrine therapy in metastatic breast cancer. For decades in frontline therapy, we only had endocrine therapy, and that’s not because other things weren’t looked at, but because nothing tended to be positive in randomized studies.

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