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Palbociclib, a selective inhibitor of cyclin-dependent kinases 4 and 6, received accelerated approved from the FDA in February 2015 for the treatment of estrogen receptor (ER)—positive breast cancer. This approval was based on the phase II, PALOMA-1 trial evaluating palbociclib in combination with letrozole in 165 postmenopausal patients. The median progression-free survival (PFS) was 20 months with palbociclib versus 10 months with letrozole alone.
While the trial demonstrated a significant improvement in PFS, says Edith A. Perez, MD, no overall survival advantage has been established. This FDA approval could be rescinded just as quickly if the phase III data do not corroborate what was seen in the phase II trial, cautions Debu Tripathy, MD.
In addition to the PFS benefit, Tripathy notes, the toxicity profile of palbociclib is fairly favorable. Patients on palbociclib therapy are at risk of neutropenia and must have a complete blood count panel repeated every 2 weeks for the first 2 months of therapy, says Carlos L. Arteaga, MD. In the study, the neutropenia rate was 50%, although there was not a higher incidence of neutropenia-related infections.
The majority of adverse events occurred in the elderly population, observes Denise A. Yardley, MD. In elderly patients, challenges such as marrow failure syndromes and poor reserve make it even more important to closely monitor patients.
The randomized, placebo-controlled phase III PALOMA-3 trial assessed the use of palbociclib in women with ER-positive, HER2-negative breast cancer who progressed during or after prior treatment with endocrine therapy. This study randomized 521 women to receive either palbociclib in combination with fulvestrant or fulvestrant plus placebo. The first analysis demonstrated that the primary endpoint, PFS, had been reached.
In the combination arm, PFS was 9.2 months compared with 3.8 months in the control arm. PALOMA-3 appears to support the hypothesis that fulvestrant is a more effective combination partner for palbociclib than letrozole, says Joyce O’Shaughnessy, MD, adding that palbociclib has already become the standard of care in her practice.