Pfizer Inc. announced that the phase 3 PALOMA-3 trial for Ibrance (palbociclib) met its primary endpoint of demonstrating an improvement in progression-free survival (PFS) for the combination of Ibrance plus fulvestrant compared with fulvestrant plus placebo in women with hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2-) metastatic breast cancer following disease progression during or after endocrine therapy.
The study was stopped early due to efficacy based on an assessment by an independent Data Monitoring Committee (DMC). These are the first randomized phase 3 trial results for Ibrance, a new anti-cancer medicine with the novel mechanism of cyclin-dependent kinase 4/6 (CDK 4/6) inhibition.
“The results of this trial are especially important because they help us understand the potential of Ibrance to improve outcomes in patients with this difficult to treat cancer. We’re gratified to be able to stop the trial early and are engaging in discussions with health authorities regarding a regulatory path forward,” said Dr. Mace Rothenberg, senior vice president of clinical development and medical affairs and chief medical officer for Pfizer Oncology.
The adverse events observed with Ibrance in combination with fulvestrant in PALOMA-3 were generally consistent with their respective known adverse event profiles. Detailed efficacy and safety results from PALOMA-3 will be submitted for presentation at the American Society of Clinical Oncology (ASCO) 2015 Annual Meeting.
Ibrance was approved by the US Food and Drug Administration (FDA) in February 2015 as a first-line treatment for women with advanced or metastatic estrogen receptor positive, human epidermal growth factor receptor 2 negative (ER+/HER2-) breast cancer. Ibrance (palbociclib), in combination with letrozole, is indicated for the treatment of postmenopausal women with ER+/HER2- advanced breast cancer as initial endocrine-based therapy for their metastatic disease. This indication is approved under accelerated approval based on PFS. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. The confirmatory phase 3 trial, PALOMA-2, is fully enrolled. Ibrance is not approved for the use being investigated in PALOMA-3 or for any indication in any market outside the US.
PALOMA-3 (also known as Study A5481023) is a randomized (2:1), multi-center, double blind Phase 3 study designed to assess the PFS of Ibrance (125 mg once daily for three out of four weeks in repeated cycles) in combination with fulvestrant versus fulvestrant (500 mg intramuscularly on days 1 and 15 of cycle 1, and then on day 1 of each subsequent 28 day cycle) plus placebo in women with HR+, HER2- metastatic breast cancer whose disease has progressed during or after endocrine therapy. PFS is defined as time from randomization to time of disease progression or death from any cause. PALOMA-3 is a multi-center trial with more than 150 global sites participating and 521 patients enrolled.