PALOMA-3 Trial of CDK 4/6 Inhibitor Palbociclib Stopped Early

Pfizer announced that the phase III trial of palbociclib was stopped early after meeting its primary endpoint of improved progression-free survival in women with HR–positive, HER2-negative metastatic breast cancer.

Pfizer recently announced that the phase III trial of its cyclin-dependent kinase 4/6 (CDK 4/6) inhibitor palbociclib was stopped early after meeting its primary endpoint of improved progression-free survival when combined with fulvestrant in women with hormone receptor (HR)-positive, HER2-negative metastatic breast cancer who had previously progressed on endocrine therapy.

The PALOMA-3 trial was stopped after an interim analysis by an independent Data Monitoring Committee. The trial randomly assigned 521 women 2:1 to 125 mg palbociclib once daily for 3 out of 4 weeks combined with fulvestrant, or to fulvestrant plus placebo. Women included in the study had HR-positive, HER2-negative breast cancer and had progressed during or after prior treatment with endocrine therapy.

Palbociclib is not currently approved for use in HR-positive, HER2-negative breast cancer. However, the drug did receive US Food and Drug Administration (FDA) accelerated approval in February 2015 based on improved progression-free survival in postmenopausal women with advanced or metastatic estrogen receptor (ER)-positive, HER2-negative breast cancer when used in combination with letrozole as a first-line treatment.

Palbociclib was approved for this indication based on a study of 165 women randomly assigned to treatment with palbociclib with or without letrozole. Women assigned the study drug combination had a median progression-free survival of 20.2 months compared with 10.2 months in the letrozole alone arm.

According to a release from Pfizer, the adverse event profile of palbociclib in the PALOMA-3 trial was consistent with the drug’s known adverse event profile. In the study of palbociclib plus letrozole, the most frequently reported serious adverse reactions in patients receiving palbociclib plus letrozole were pulmonary embolism (3 of 83; 4%) and diarrhea (2 of 83; 2%).

The most common adverse events were neutropenia, leukopenia, fatigue, anemia, upper respiratory infection, nausea, stomatitis, alopecia, diarrhea, thrombocytopenia, decreased appetite, vomiting, asthenia, peripheral neuropathy, and epistaxis.

According to the release, the full efficacy and safety results of the PALOMA-3 trial will be presented at the 2015 American Society of Clinical Oncology (ASCO) Annual Meeting.