FROM THE NEW ENGLAND JOURNAL OF MEDICINE
Adding the CDK inhibitor palbociclib to standard endocrine therapy (letrozole) extended progression-free survival in a manufacturer-sponsored phase III trial of advanced ER-positive, HER2-negative breast cancer, investigators reported in the New England Journal of Medicine.
Compared with placebo, palbociclib significantly improved progression-free survival regardless of patient age, patient performance status, site of metastasis, prior use of chemotherapy, prior use of endocrine therapy, length of the disease-free interval before progression, or the cancer’s histologic subtype. “The median progression-free survival of 24.8 months in [our study] is longer than that seen in other phase III studies involving women with advanced breast cancer. Whether this progression-free survival will result in longer overall survival is uncertain until further follow-up is completed,” wrote Richard S. Finn, MD, of the University of California, Los Angeles, and his associates.
The investigators assessed the safety and performance of additive palbociclib in 666 women treated at 186 sites in 17 countries. The median patient age was 61-62 years. Approximately half of the study participants had visceral disease at baseline, 62.8% had received prior systemic therapy, and 40.7% had a disease-free interval of more than 12 months. They were randomly assigned to receive either 125 mg of oral palbociclib per day in 4-week cycles (444 patients) or a matching placebo (222 patients), in addition to 2.5 mg of daily oral letrozole, and were followed for a median of 23 months.
The primary endpoint – time to disease progression or death – was 24.8 months with active treatment, compared with 14.5 months with placebo, for a hazard ratio of 0.58. The rate of disease progression or death was 43.7% in the palbociclib group, compared with 61.7% in the placebo group. In addition, the rate of objective tumor response was 42.1% with palbociclib, compared with 34.7% with placebo, they reported.
“Data on overall survival were immature at the time of this analysis of the primary end point, and the final overall survival analysis will be performed when a total of 390 deaths occur, per protocol and in agreement with regulatory agencies,” Dr. Finn and his associates said (N Engl J Med. 2016 Nov. 17. doi: 10.1056/NEJMoa1607303). As expected, the rate of hematologic adverse events was high with palbociclib. “Although the incidence of neutropenia of any grade in the palbobiclib/letrozole group was 79.5% in the current study, the incidence of febrile neutropenia was lower than 2%. In addition, the rate of permanent treatment discontinuation associated with an adverse event did not differ significantly between the two study groups, although dose reductions were more common with palbociclib than with placebo,” they added.
Myelotoxic effects have been managed successfully with appropriate supportive care and dose reductions. At the time of this analysis, 199 patients (44.8%) in the active-treatment group were still taking palbociclib and letrozole, the investigators said.
This study was supported by Pfizer. Dr. Finn reported receiving grants, personal fees, and other support from Pfizer, Bayer, Novartis, and Bristol-Myers Squibb. His associates reported ties to numerous industry sources.
