368P - Clinical Patterns of Palbociclib Associated Neutropenia in the Paloma-1/Trio-18 Trial

Abstract

ABSTRACT Background: Palbociclib (P) an oral selective, reversible CDK4/6 inhibitor, inhibits cell proliferation by halting cell cycle progression. PALOMA-1/TRIO-18, a randomized ph 2 study evaluated the efficacy and safety of P + letrozole (L) in women with post-menopausal ER + , HER2-advanced breast cancer (ABC). Progression-free survival was doubled over L alone. Neutropenia was the most frequently reported adverse event (AE). In preclinical studies evaluating the bone marrow, P did not appear to affect well-differentiated progenitor cells or mature peripheral neutrophils but induces quiescence (G1 arrest) of early multipotent progenitor cells (S Johnson, JCI 2010). These findings suggest P may induce neutropenia by a different mechanism than chemotherapy (CT). Methods: To characterize patterns of neutropenia with P +L in women with ABC, we retrospectively evaluated ph 2 data from the P + L arm in PALOMA-1. Safety assessments occurred at baseline and D1 of each cycle; blood counts occurred every 2 wk for 2 cycles and on D1 of subsequent cycles. Since women experienced multiple episodes during treatment, we analyzed all episodes in aggregate based on laboratory data per CTCAE 3.0. Results: In the P + L arm (n = 83), P was given 125 mg daily 3 weeks on /1 week off. The median treatment duration was 13.8 m (1-41). Per lab data, G3/G4 neutropenia occurred in 57%/5 % of pts. Median time to onset for first episode of any grade and ≥G3 neutropenia was 15 d (13-117) and 28 d (14-669) and median time from first dose to lowest ANC count was 43 d (14-961). The median duration for a ≥G3 episode was 7 d (1-112). 45% of pts had cycle delay with median of 4 d for any AE. 33% of pts had dose interruptions with median 2.5 d (1-16) and first onset at 2.5 m for any AE. The mean relative dose intensity was 94% (SD 26%). Discontinuation of study drug for neutropenia was uncommon (n= 5 pts; 6%). Neutropenia was not associated with prior CT, tumor grade, body weight or age. Conclusions: Findings suggest neutropenia with P +L is common but it differs from that seen with CT in that it is not commonly associated with fever, is self-limited, and characterized by recovery after a brief dose interruption or cycle delay. This is consistent with its proposed mechanism of action. Disclosure: R. Finn: This study was funded by Pfizer, Inc. Pfizer, Inc. has paid for travel; C. Huang-Bartlett, P. Schnell, S. Kim, S. Randolph and K. Wang: Employee of Pfizer, Inc. All other authors have declared no conflicts of interest.