FDA Approval: Palbociclib for the Treatment of Postmenopausal Patients with Estrogen Receptor-Positive, HER2-Negative Metastatic Breast Cancer
Cet article présente les données cliniques ayant servi de base à l'autorisation de mise sur le marché américain du palbociclib pour le traitement des patientes atteintes d'un cancer métastatique du sein ER+ HER2- après la ménopause
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 1/2 trial (PALOMA-1) in 165 patients randomized to palbociclib (125mg orally daily for 21 consecutive days, followed by 7 days off treatment) plus letrozole (2.5mg orally daily) or letrozole alone. The Phase 2 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 to patients receiving letrozole alone [HR 0.488 (95% CI: 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 which may be contingent upon verification and description of clinical benefit in the on-going and fully accrued confirmatory trial, PALOMA-2.