Background: Palbociclib (PA), a CDK4/CDK6 inhibitor, has been shown in clinical trials to prolong progression free survival (PFS) in HR+/Her-2 negative MBC when combined with an aromatase inhibitor (AI) or fulvestrant (FULV). This study assessed real world outcomes of HR+ MBC patients (pts) treated with PA/endocrine therapy (ET).
Methods: This is a retrospective, single institution review of
... [Show full abstract] HR+ MBC pts treated with PA plus either an AI or FULV from 2015-2017. The primary outcome was progression-free survival (PFS) as assessed by the clinician based on radiological and/or clinical criteria. Tolerability and observed toxicities with PA and overall survival (OS)—defined as date of initial PA treatment to date of death— were also evaluated as secondary outcomes.
Results: 411 women with HR+ MBC who received PA were identified. 94% were HER-2 negative. Median and average follow up duration were 10.2 and 11.3 months, respectively. 55% received PA/letrozole (LTZ), 6% PA/other AI, and 38% PA/FULV. PA/ET was initiated as 1st, 2nd, 3rd, or 4th line and beyond in 36%, 26%, 13%, and 25% of pts, respectively. As of 1/3/2018, 310 patients (76%) were still alive, 186 patients (45%) had progressed on PA with 48% currently on PA. The estimated median PFS for PA/LTZ was 8.92 months (95% CI 6.16-11.0)—similar to that for PA/other AI. For PA/FULV the estimated median PFS was 10.3 months (95% CI 8.16-12.3). Most pts (65%) received PA/LTZ in the 2nd line and beyond. For pts who received PA/LTZ as 1st line therapy, the estimated PFS was 15.1 months (95% CI 12.3-infinity). The median OS could not be calculated because of insufficient number of deaths. In the overall cohort, the 1 and 2 year OS rates were 78% and 53.1%, respectively. PA was dose reduced in 27% of pts due to drug toxicity, most commonly because of neutropenia. Permanent discontinuation of PA due to toxicity was infrequent occurring only in 7% of pts.
Conclusions: Among HR+ MBC pts in non-clinical trial setting, the estimated PFS on PA/fulvestrant was comparable to PALOMA-3, however our observed PFS with PA/letrozole as 1st line therapy was shorter than that reported in PALOMA-2. PA was well tolerated with manageable toxicity and low drug discontinuation rate.