Abstract P5-19-19: Impact of adding palbociclib to letrozole on pain severity and pain interference with various activities of daily life in patients with ER+, HER2- metastatic breast cancer as first line treatment
Authors: Bell Timothy , Crown John Paul , Lang Istvan , Bhattacharyya Helen , Zanotti Giovanni , Randolph Sophia , Kim Sindy , Huang Xin , Huang Bartlett Cynthia , Finn Richard , Slamon Dennis 
Published: May 2015

Abstract
Background
Palbociclib, a selective inhibitor of CDK-4/6, prevents DNA synthesis by blocking cell cycle progression. A randomized Phase 2 study of palbociclib (P) 125 mg QD for 3 weeks followed by 1 week off plus letrozole (L) 2.5 mg QD continuously compared to L alone was conducted. A secondary objective of the study was to assess the impact of adding P in combination with L compared to L alone on pain severity and pain interference with various activities of daily life.
Methods
This Phase 2 trial was designed to evaluate P+L in front-line ER+/HER2- metastatic breast cancer (MBC) compared to L alone. The primary endpoint was investigator assessed progression-free survival (PFS) defined as time from randomization to objective progression or death. Patient reported outcomes of pain severity (PS) and pain interference (PI) with various activities of daily life were assessed using the Brief Pain Inventory (BPI) at baseline and day 1 of each cycle thereafter. The PS and PI scores were summarized by cycle using observed values as well as changes from baseline.
Results
The final analysis of primary endpoint showed a statistically significant improvement in PFS for the P+L arm (20.2 months) vs. L arm (10.2 months) with hazard ratio (HR)=0.488 (95% CI: 0.319, 0.748) and 1-sided p=0.0004. The most common adverse events in the P+L arm were neutropenia, leukopenia, fatigue, and anemia.
For the PS scale, patients in the P+L arm showed numerically lower scores and greater reductions from baseline than the L arm, until the later cycles, when the number of patients had decreased to a small number. The difference between treatment arms in the mean change from baseline was statistically significant at some of the earlier cycles (Cycles 5, 6, 7, 8, 10, 12; p&lt;0.05; no adjustments were made for multiplicity) representing a numerically greater decrease in the pain experienced by patients in the P+L arm compared with the L arm.
For the PI score, observed mean scores for both treatment arms appeared to be stable over time until the later cycles, when the number of patients had decreased to a small number. Patients in the P+L treatment arm also generally showed a consistently greater numeric reduction from baseline in pain interference (ie, a decrease in PI on daily activities) until later cycles although without reaching statistical significance at any cycle.
Conclusions
The addition of palbociclib to letrozole was associated with increased efficacy without negatively impacting pain severity or pain interference on daily activities.
Citation Format: Timothy Bell, John Paul Crown, Istvan Lang, Helen Bhattacharyya, Giovanni Zanotti, Sophia Randolph, Sindy Kim, Xin Huang, Cynthia Huang Bartlett, Richard Finn, Dennis Slamon. Impact of adding palbociclib to letrozole on pain severity and pain interference with various activities of daily life in patients with ER+, HER2- metastatic breast cancer as first line treatment [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P5-19-19.