Date: 2015-05-30
Type of information: Presentation of results at a congress
phase: 3
Announcement: presentation of results at the 51st Annual Meeting of the American Society of Clinical Oncology (ASCO)
Company: Pfizer (USA - NY)
Product: Ibrance® (palbociclib)
Action
mechanism: cyclin dependant kinase inhibitor. Ibrance® was approved by the U.S. 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.i This indication is approved under accelerated approval based on PFS.i 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 U.S.
Disease: HR+, HER2- metastatic breast cancer
Therapeutic area: Cancer - Oncology
Country: Australia, Belgium, Canada, Germany, Ireland, Italy, Japan, Republic of Korea, The Netherlands, Portugal, Romania, Russian Federation, Taiwan, Turkey,Ukraine, UK,USA
Trial
details: 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. (NCT01942135)
Latest
news: * On May 30, 2015, Pfizer 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 will be featured during the 51st Annual Meeting of the American Society of Clinical Oncology (ASCO) (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. 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 (See below). 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 U.S. label. * On April 15, 2015, Pfizer 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®. 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 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.i This indication is approved under accelerated approval based on PFS.i 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.
