TY - JOUR
T1 - FDA approval
T2 - Palbociclib for the treatment of postmenopausal patients with estrogen receptor-positive, HER2-negative metastatic breast cancer
AU - Beaver, Julia A.
AU - Amiri-Kordestani, Laleh
AU - Charlab, Rosane
AU - Chen, Wei
AU - Palmby, Todd
AU - Tilley, Amy
AU - Zirkelbach, Jeanne Fourie
AU - Yu, Jingyu
AU - Liu, Qi
AU - Zhao, Liang
AU - Crich, Joyce
AU - Chen, Xiao Hong
AU - Hughes, Minerva
AU - Bloomquist, Erik
AU - Tang, Shenghui
AU - Sridhara, Rajeshwari
AU - Kluetz, Paul G.
AU - Kim, Geoffrey
AU - Ibrahim, Amna
AU - Pazdur, Richard
AU - Cortazar, Patricia
N1 - Publisher Copyright:
©2015 AACR.
PY - 2015/11/1
Y1 - 2015/11/1
N2 - On February 3, 2015, the FDA granted accelerated approval to palbociclib (IBRANCE, Pfizer Inc.), an inhibitor of cyclin-dependent kinases 4 and 6 (CDK4 and CDK6), for use in combination with letrozole for the treatment of postmenopausal women with estrogen receptor (ER)-positive, HER2-negative advanced breast cancer as initial endocrine-based therapy for their metastatic disease. The approval is based on a randomized, multicenter, open-label phase I/II trial (PALOMA-1) in 165 patients randomized to palbociclib (125 mg orally daily for 21 consecutive days, followed by 7 days off treatment) plus letrozole (2.5 mg orally daily) or letrozole alone. The phase II portion of the trial was divided into two cohorts: cohort 1 enrolled 66 biomarker-unselected patients and cohort 2 enrolled 99 biomarker-positive patients. The major efficacy outcome measure was investigator-assessed progression-free survival (PFS). A large magnitude of improvement in PFS was observed in patients receiving palbociclib plus letrozole compared with patients receiving letrozole alone (HR, 0.488; 95% confidence interval, 0.319-0.748). Multiple sensitivity analyses were supportive of clinical benefit. The most common adverse reaction in patients receiving palbociclib plus letrozole was neutropenia. This article summarizes the FDA thought process and data supporting accelerated approval based on PALOMA-1 that may be contingent upon verification and description of clinical benefit in the ongoing and fully accrued confirmatory trial PALOMA-2.
AB - On February 3, 2015, the FDA granted accelerated approval to palbociclib (IBRANCE, Pfizer Inc.), an inhibitor of cyclin-dependent kinases 4 and 6 (CDK4 and CDK6), for use in combination with letrozole for the treatment of postmenopausal women with estrogen receptor (ER)-positive, HER2-negative advanced breast cancer as initial endocrine-based therapy for their metastatic disease. The approval is based on a randomized, multicenter, open-label phase I/II trial (PALOMA-1) in 165 patients randomized to palbociclib (125 mg orally daily for 21 consecutive days, followed by 7 days off treatment) plus letrozole (2.5 mg orally daily) or letrozole alone. The phase II portion of the trial was divided into two cohorts: cohort 1 enrolled 66 biomarker-unselected patients and cohort 2 enrolled 99 biomarker-positive patients. The major efficacy outcome measure was investigator-assessed progression-free survival (PFS). A large magnitude of improvement in PFS was observed in patients receiving palbociclib plus letrozole compared with patients receiving letrozole alone (HR, 0.488; 95% confidence interval, 0.319-0.748). Multiple sensitivity analyses were supportive of clinical benefit. The most common adverse reaction in patients receiving palbociclib plus letrozole was neutropenia. This article summarizes the FDA thought process and data supporting accelerated approval based on PALOMA-1 that may be contingent upon verification and description of clinical benefit in the ongoing and fully accrued confirmatory trial PALOMA-2.
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U2 - 10.1158/1078-0432.CCR-15-1185
DO - 10.1158/1078-0432.CCR-15-1185
M3 - Article
C2 - 26324739
AN - SCOPUS:84947204419
SN - 1078-0432
VL - 21
SP - 4760
EP - 4766
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 21
ER -