Palbociclib Combo Approved by FDA for Pretreated HR+/HER2-Negative Breast Cancer

The approval is based on findings from the phase III PALOMA-3 trial, in which adding palbociclib to standard fulvestrant more than doubled progression-free survival (PFS) in pretreated patients with HR-positive, HER2-negative breast cancer. Palbociclib delayed disease progression by almost 5 months.

Palbociclib was initially approved by the FDA in February 2015 for use in combination with letrozole as a frontline treatment for postmenopausal women with ER-positive, HER2-negative metastatic breast cancer.

“Today's news gives more women with metastatic breast cancer the opportunity to benefit from this first-in-class medicine," said Liz Barrett, global president and general manager, Pfizer Oncology. “Since Ibrance was approved just over 1 year ago, physicians across the United States have embraced it as a standard of care in the first-line setting. The expanded approval of Ibrance is supported by a robust body of evidence."

The double-blind, multicenter PALOMA-3 study randomized 521 patients with metastatic breast cancer whose disease progressed on or following endocrine treatment in a 2:1 ratio to fulvestrant plus either palbociclib (n = 347) or placebo (n = 174).

Fulvestrant was administered at 500 mg (IM) on days 1 and 15 of cycle 1, and then on day 1 of each cycle thereafter, and patients received oral palbociclib at 125 mg/day continuously for the first 3 weeks of each cycle, followed by 1 week off. Treatment cycles were 28 days for both arms. Goserelin was also administered to pre- and perimenopausal patients.

Baseline patient data were similar between the 2 arms. The median patient age was 57 and 56 years in the palbociclib and placebo arms, respectively. Patients were stratified by menopausal status, sensitivity to prior hormonal therapy, and visceral metastases. In both treatment arms, 79% of patients were sensitive to previous endocrine treatment, 60% had visceral disease, and 79% were postmenopausal. One previous line of chemotherapy for advanced disease was permitted, of which 33% of patients in the overall population had received.

PFS was the primary outcome measure, with secondary objectives focusing on overall survival (OS), response, and safety. Following 195 PFS events, the trial was halted in April 2015 after an independent panel determined the study had met its primary endpoint.

Median PFS was 9.5 months with the palbociclib combination versus 4.6 months in the placebo arm (HR, 0.461; 95% CI 0.360-0.591; P <.0001). The PFS benefit was observed regardless of menopause status and remained consistent across all prespecified patient subgroups. OS data are not yet mature.

The overall response rate was 24.6% for the palbociclib arm compared with 10.9% for the placebo plus fulvestrant arm. The duration of response was 9.3 months versus 7.6 months, respectively.

The most common all-grade adverse events for the palbociclib versus the control arm included neutropenia (83% vs 4%), leukopenia (53% vs 5%), infections (47% vs 31%), fatigue (41% vs 29%), nausea (34% vs 28%), anemia (30% vs 13%), stomatitis (28% vs 13%), headache (26% vs 20%), diarrhea (24% vs 19%), thrombocytopenia (23% vs 0%), constipation (20% vs 16%), vomiting (19% vs 15%), alopecia (18% vs 6%), rash (17% vs 6%), decreased appetite (16% vs 8%), and pyrexia (13% vs 5%).