FDA Approves Ibrance Plus Faslodex for Hormone Receptor-Positive Breast Cancer

The U.S. Food and Drug Administration (FDA) has approved Ibrance (palbociclib) for use in combination with Faslodex (fulvestrant) in pretreated patients with hormone receptor (HR)-positive, HER2-negative metastatic breast cancer, according to the developer of the oral medication, Pfizer.

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

The FDA initially approved Ibrance in February 2015 for use in combination with Femara (letrozole) as a frontline treatment for postmenopausal women with estrogen receptor-positive, HER2-negative metastatic breast cancer.

“There currently is no cure for metastatic breast cancer, so ongoing treatment is usually needed to control the spread of the disease,” Marisa Weiss, chief medical officer and founder, Breastcancer.org, said in a statement. “That's why the availability of a first-of-its-kind treatment option like Ibrance for women dealing with HR+/HER2- metastatic disease represents a very important advance.”

Palbociclib is an oral medication that targets cyclin-dependent kinases (CDK4 and CDK6), which promote tumor cell growth in HR-positive breast cancer. In the multicenter PALOMA-3 study, 521 patients with metastatic breast cancer whose disease progressed on or following endocrine treatment were randomized in a 2:1 ratio to Faslodex plus either Ibrance (n = 347) or placebo (n = 174).

Faslodex was administered at 500 mg on days 1 and 15 of cycle 1, and then on day 1 of each cycle thereafter, and patients received oral Ibrance 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 Ibrance and placebo arms, respectively. Patients were stratified by menopausal status, sensitivity to prior hormonal therapy, and visceral metastases.

In both treatment arms, 79 percent of patients were sensitive to previous hormonal therapy, 60 percent had visceral disease, and 79 percent were postmenopausal. One previous line of chemotherapy for advanced disease was permitted, of which 33 percent 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 Ibrance combination versus 4.6 months in the placebo arm, representing a 54 percent reduction in the risk of progression or death (hazard ratio [HR], 0.461; 95 percent confidence interval [CI], 0.360-0.591; P <.0001). The PFS benefit was observed regardless of menopause status and remained consistent for all patients. OS data were not yet available at the time of the analysis.

The overall response rate was 24.6 percent for the Ibrance arm compared with 10.9 percent for the placebo plus Faslodex arm. The duration of response was 9.3 months versus 7.6 months, respectively.

The most common all-grade adverse events for the Ibrance versus the control arm included abnormally low levels of neutrophils (83 percent vs 4 percent) and white blood cells (53 percent vs 5 percent), which led to an increased rate of infections (47 percent vs 31 percent).

Additionally, patients experienced fatigue (41 percent vs 29 percent), nausea (34 percent vs 28 percent), anemia (30 percent vs 13 percent), mouth sores (28 percent vs 13 percent), headache (26 percent vs 20 percent), diarrhea (24 percent vs 19 percent), blood platelets deficiency (23 percent vs 0 percent), constipation (20 percent vs 16 percent), vomiting (19 percent vs 15 percent), alopecia (18 percent vs 6 percent), rash (17 percent vs 6 percent), decreased appetite (16 percent vs 8 percent), and fever (13 percent vs 5 percent).

Neutropenia (66 percent) and leukopenia (31 percent) were the most common grade 3/4 AEs. The most frequently reported serious AEs in the palbociclib arm were infections, pyrexia, neutropenia, and pulmonary embolism. Dose reductions related to AEs occured in 36 percent of patients, and 6 percent of patients discontinued treatment due to AEs.

“Today's news gives more women with metastatic breast cancer the opportunity to benefit from this first-in-class medicine," Liz Barrett, global president and general manager, Pfizer Oncology, said in a statement. “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.”

Turner NC, Ro J, Andre F, et al. PALOMA3: A double-blind, phase III trial of fulvestrant with or without palbociclib in pre- and post-menopausal women with hormone receptor-positive, HER2-negative metastatic breast cancer that progressed on prior endocrine therapy. J Clin Oncol. 2015;33 (suppl; abstr LBA502).