Abstract PD5-06: Adjuvant palbociclib plus endocrine therapy for hormone receptor positive/HER2 negative breast cancer: A phase II feasibility study
Authors: Mayer EL , DeMichele AM , Guo H , Miller KD , Rugo HS , Schneider B , Waks AG , Come SE , Mulvey T , Huang Bartlett C , Koehler M , Barry W , Winer EP , Burstein HJ 
Published: February 2018

Abstract
Background:
The CDK4/6 inhibitor palbociclib (P) combined with endocrine therapy (ET) prolongs progression-free survival in previously untreated and treated hormone receptor positive/HER2 negative (HR+/HER2-) metastatic breast cancer (MBC). The most common toxicity with P is neutropenia, typically non-cumulative and uncomplicated. Given observed benefits of P in metastatic BC, this single arm phase II trial was designed to determine the feasibility and toxicity of combination adjuvant P and ET for HR+/HER2- early BC (EBC).
Methods:
Eligible patients (pts) had HR+/HER2- stage II (not T2N0)-III EBC, with prior completion of 3-24 mo of ET (either AI or tamoxifen) without significant adverse events (AE). Pts received P at 125 mg daily, 3 wk on/1 wk off in a 28d cycle, plus continuous ET, for planned duration 2 yrs. Pts were removed from study for toxicity, non-adherence, or other events related to tolerability; pts who recurred or completed 2 yrs of therapy were censored for the primary endpoint. The primary objective was to evaluate the treatment discontinuation rate at 2 yrs; a rate of &gt;50%, would indicated a non-feasible treatment duration (null hypothesis). Discontinuation rates at 2 yrs are estimated by Kaplan Meier with 95% confidence bands. A sample size of 160 pts provided 92% power to reject the null hypothesis using a one-sided alpha = 0.025 if the true rate of discontinuation is &lt;33.3%, and accounting for a censoring rate of up to 20% over the 2 yrs. Secondary endpoints include toxicity, adherence, QOL, and pharmacogenomics.
Results:
Between 3/2014 and 11/2015, 162 pts initiated P; the majority had stage III EBC (52%) and received prior chemotherapy (63%). As of 05/2017, 120 (74%) have completed at least 1 yr of P + ET, and 50 (31%) have completed 2 yrs of P + ET. Early discontinuation of protocol treatment was reported for 59 pts (36%), including 49 events (30%) related to protocol-mandated (9%) and non-mandated (21%) tolerability. The cumulative rate of all discontinuations was 15.1% at 6 mos, 20.9% at 12 mos and 27.8% at 18 mos. Half of all non-mandated discontinuations occurred within the first 6 mos of initiation of therapy, and the rate decreased with greater provider and pt education. Median duration of pts still on treatment is 20 mos (inter-quartile range: 18 to 21 mos). The rate of grade 3/4 neutropenia was 77%, with 0 cases of febrile neutropenia. Other common all-grade P-related AE &gt; 20% included fatigue 65%, alopecia 25%, mucositis 24%, and anemia 24%. 32% of pts required one dose reduction, 16% required two. There have been 2 BC recurrence events and 1 chemotherapy-related AML. Updated data for the primary analysis of feasibility and tolerability, as well as pharmacogenomics, QOL, and adherence, will be presented.
Conclusions:
In this single arm phase II trial, the majority of pts have completed at least 1 year of adjuvant P + ET therapy, with no new toxicity signals. Non-protocol discontinuations have decreased with education. Updated results for the primary analysis will be presented. As in the MBC setting, extended duration palbociclib appears feasible and tolerable for most pts. The efficacy of 2 years of P and ET will be addressed by the phase III PALLAS trial (NCT NCT02513394).
Citation Format: Mayer EL, DeMichele AM, Guo H, Miller KD, Rugo HS, Schneider B, Waks AG, Come SE, Mulvey T, Huang Bartlett C, Koehler M, Barry W, Winer EP, Burstein HJ. Adjuvant palbociclib plus endocrine therapy for hormone receptor positive/HER2 negative breast cancer: A phase II feasibility study [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr PD5-06.