Palbociclib, a cyclin-dependent kinase 4/6 inhibitor, has been approved by the Food and Drug Administration for treating postmenopausal women with estrogen receptor–positive, human epidermal growth factor receptor 2–negative advanced breast cancer as initial endocrine-based therapy for metastatic disease, in combination with letrozole.

The accelerated approval was based on a randomized phase II study of 165 postmenopausal women with ER-positive, HER2-negative metastatic breast cancer, who had not been treated for advanced disease, in which investigators found a progression-free survival rate of about 20.2 months among the women treated with the combination, compared with about 10.2 months among those treated with letrozole, an aromatase inhibitor, alone. Overall survival results are not yet available, according to the Feb. 3 Food and Drug Administration statement announcing the approval.

“The addition of palbociclib to letrozole provides a novel treatment option to women diagnosed with metastatic breast cancer,” Dr. Richard Pazdur, director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research, said in the statement. Palbociclib was approved under the FDA Accelerated Approval Program, which “allows approval of a drug to treat a serious or life-threatening disease based on clinical data showing the drug has an effect on a surrogate endpoint reasonably likely to predict clinical benefit to patients,” and makes the drug available to patients earlier while the manufacturer conducts trials to confirm the benefits, according to the FDA. The indications and usage section of the prescribing information includes the statement that “continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.”

Neutropenia, leukopenia, fatigue, anemia, upper respiratory infection, nausea, stomatitis, alopecia, diarrhea, thrombocytopenia, decreased appetite, vomiting, lack of energy and asthenia, peripheral neuropathy, and epistaxis were the most common adverse effects associated with treatment, according to the FDA statement.

“Healthcare professionals are advised to monitor complete blood count prior to start of therapy and at the beginning of each cycle, as well as on day 14 of the first two cycles, and as clinically indicated,” the statement said.

The recommended starting dose for palbociclib is 125 mg once a day (with food) for 21 days followed by 7 days off treatment.

Palbociclib inhibits cyclin-dependent kinase (CDK) 4 and 6, involved in promoting the growth of cancer cells. Letrozole (Femara), also taken orally, is approved for treatment of breast cancer in postmenopausal women, as adjuvant treatment for hormone receptor–positive early breast cancer, extended adjuvant treatment of early breast cancer for patients who have received prior standard adjuvant tamoxifen therapy, and as first- and second-line treatment of hormone receptor–positive or unknown advanced breast cancer.

In a statement released by the University of California, Los Angeles, Jonsson Comprehensive Cancer Center, the principal investigator of the study that led to the approval, Dr. Richard S. Finn, pointed out that palbociclib is the first drug in its class to be approved. In the statement, Dr. Dennis J. Slamon, director of the Revlon/UCLA Women’s Cancer Research Program and Clinical/Translational Research at the Jonsson Cancer Center, said that he believes that palbociclib will become “a standard treatment approach for postmenopausal women with ER+/HER2– metastatic breast cancer.” He added that the magnitude of the benefit seen in the phase II study “was very gratifying and reminiscent of results we saw when we conducted the initial studies on Herceptin in HER2+ breast cancers 2 decades ago.”

Dr. Finn reported the of the phase II study at the annual meeting of the American Association for Cancer Research in April. He and Dr. Slamon are investigators in the phase III confirmatory trial of palbociclib in over 600 women, which has completed enrollment, according to the UCLA release.

Pfizer will market palbociclib as Ibrance.