Pfizer Inc. announced study results demonstrating palbociclib in combination with fulvestrant was superior to treatment with a standard of care, fulvestrant, by significantly extending progression-free survival (PFS) in women with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer whose disease has progressed during or after endocrine therapy (HR 0.42, median PFS, 9.2 vs. 3.8 months, in their respective arms, p<0.000001).

Results from the phase 3 PALOMA-3 study featured in a press briefing during the 51st Annual Meeting of the American Society of Clinical Oncology (ASCO) and will be presented as a late-breaker on Monday, June 1 at 8:00 a.m. CDT (Abstract #LBA502). The results will also be simultaneously published online by The New England Journal of Medicine. The Principal Investigator for the study, Nicholas C. Turner, MD, PhD, consultant medical oncologist at The Royal Marsden and Institute of Cancer Research in London, United Kingdom, will present these data.

“The current treatment options available for patients with this type of metastatic breast cancer present challenges for physicians and patients, as demonstrated by the limited clinical benefit of additional lines of endocrine therapy, and by the difficult side effects of chemotherapy,” said Dr. Turner. “The PALOMA-3 results demonstrate that palbociclib in combination with fulvestrant more than doubled the time before disease progression compared to fulvestrant alone, and suggest that palbociclib could be a promising treatment option for women with HR+, HER2- metastatic breast cancer after progression on endocrine therapy.”

“The results of PALOMA-3 are compelling and provide evidence that could potentially expand the role of palbociclib as an innovative first-in-class therapy for patients with metastatic breast cancer,” said Dr. Mace Rothenberg, senior vice president of Clinical Development and Medical Affairs and chief medical officer for Pfizer Oncology.

PALOMA-3 (also known as Study A5481023) is a multi-center trial with more than 140 global sites participating and 521 patients enrolled. The study is a randomized (2:1), double-blind phase 3 study designed to assess the PFS of palbociclib (125 mg once daily orally for three out of four weeks in each cycle) in combination with fulvestrant (500 mg intramuscularly on days 1 and 15 of cycle 1, and then on day 1 of each subsequent 28 day cycle) versus fulvestrant plus placebo in pre/perimenopausal and postmenopausal women with HR+, HER2- metastatic breast cancer whose disease has progressed during or after endocrine therapy. Pre/perimenopausal women also received ovarian suppression (goserelin). PFS is defined as time from randomization to time of disease progression or death from any cause.

As previously disclosed, the PALOMA-3 study met its primary endpoint of PFS at the interim analysis and was stopped early in April 2015 due to efficacy based on an assessment by an independent Data Monitoring Committee (DMC). Benefit from palbociclib was also demonstrated across all pre-specified subgroups, including both pre/perimenopausal and postmenopausal patients. At the time of the PFS analysis, overall survival (OS) data was immature.

The adverse events observed with palbociclib in combination with fulvestrant in PALOMA-3 were consistent with their respective labeled adverse event profiles. The most common adverse events reported for the palbociclib-fulvestrant group were neutropenia, leukopenia, fatigue and nausea. The rate of febrile neutropenia (0.6%) was the same in both arms in the study. Serious adverse events were balanced across arms in the study. The discontinuation rate due to adverse events was 2.6% on the palbociclib plus fulvestrant arm and 1.7% on the fulvestrant plus placebo arm.

Based on the results of PALOMA-3, Pfizer is in discussions with global regulatory authorities to determine next steps to potentially make palbociclib available for women with HR+, HER2- metastatic breast cancer whose disease has progressed following endocrine therapy. As previously disclosed, Pfizer intends to file a Marketing Authorisation Application for palbociclib to the European Medicines Agency (EMA) in the second half of 2015. In addition, Pfizer will work closely with the FDA to review these data and determine next steps for potential inclusion in the US label.

Palbociclib, under the brand name Ibrance, was approved in combination with letrozole by the US Food and Drug Administration (FDA) in February 2015 for the treatment of postmenopausal women with estrogen receptor-positive (ER+)/HER2- advanced breast cancer as initial endocrine-based therapy for their metastatic disease.1 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.

Ibrance (palbociclib) is an oral inhibitor of cyclin-dependent kinases (CDKs) 4 and 6.1 CDKs 4 and 6 are key regulators of the cell cycle that trigger cellular progression.2,3 Ibrance is indicated in the US for use in combination with letrozole for the treatment of postmenopausal women with estrogen receptor-positive, human epidermal growth factor receptor 2-negative (ER+/HER2-) advanced breast cancer as initial endocrine-based therapy for their metastatic disease.

The effectiveness of Ibrance in these patients is based on a study that measured progression-free survival. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.