Abstract P6-17-01: Central nervous system metastases at diagnosis in patients with HER2+ MBC: Baseline characteristics, HER2-targeted treatments and clinical outcomes from the SystHERs registry
Authors: Cobleigh M , Hurvitz S , O'Shaughnessy J , Mason G , Yardley D , Jahanzeb M , Brufsky A , Rugo H , Swain S , Kaufman P , Tripathy D , Mayer M , Ogale S , Yoo B , Beattie M 
Published: May 2016

Abstract
Introduction
HER2+ MBC patients with CNS metastases are often excluded from clinical trials. The Systemic Therapies for HER2+ Metastatic Breast Cancer Registry (SystHERs), a real-world, prospective registry study, is uniquely positioned to evaluate this understudied population over time. Here we describe the clinical characteristics, HER2-targeted treatments, and survival outcomes of patients with and without CNS metastases at MBC diagnosis.
Methods
SystHERs is enrolling patients with HER2+ MBC who are &gt;18 years of age and within 6 months of MBC diagnosis. Patients with CNS metastases are identified by their physicians according to local clinical practice. Patient-reported outcomes are obtained at enrollment and throughout the study. Median PFS and OS were estimated using the Kaplan-Meier method and Cox regressions were used to estimate hazard ratios (HRs).
Results
As of February 2, 2015, data are available for 579 eligible patients, of whom 53 (9%) had CNS metastases at MBC diagnosis (median time from diagnosis to enrollment was 2.3 months). Clinical characteristics and patient-reported functioning in patients with and without CNS metastases at MBC diagnosis are shown in Table 1.
Table 1. CNS (n=53)Non-CNS (n=526)Median age (range)57 (36-86)56 (21-88)De novo MBCa, n (%)15 (28)275 (52)Hispanic or Latina, n (%)7 (13)52 (10)White, n (%)46 (87)407 (77)BMI (range)29 (17-43)28 (9-60)ECOG PS (0-1), n (%)36 (68)471 (90)Hormone receptor status, n (%) ER+,PR+21 (40)247 (47)ER+,PR-11 (21)106 (20)ER-,PR+010 (2)ER-, PR-21 (40)153 (29)FACT-Bb,c, median (IQR)(n=42)(n=422) 93 (78-110)102 (85-118)Rotterdam Symptom Checklistb,d, median (IQR)(n=43)(n=429) 75 (54-88)88 (67-100)General HRQOLb,d, median (IQR)(n=43)(n=434) 60 (50-80)80 (61-90)aMetastases confirmed within approximately 90 days of diagnosis. bHigher scores indicate better functioning. cScale range 0-144. dScale range 0-100.
First-line MBC treatment data are available for 502 patients, of whom 488 (97%) reported first-line HER2-targeted therapy at the time of data cutoff (Table 2).
Table 2.First-line HER2-targeted therapy, n (%)CNS (n=40)Non-CNS (n=448)Any trastuzumab + pertuzumab22 (55)313 (70)Any trastuzumab, no pertuzumab11 (28)117 (26)Any lapatinib14 (35)14 (3)Any T-DM15 (13)29 (6)
At a median follow-up time of 12.9 months, median first PFS was 8 months in patients with CNS metastases, and 11.9 months in those without (HR = 0.442; 95% CI 0.304 – 0.641). Median OS was 22 months in patients with CNS metastases, and was not reached in patients without CNS metastases (HR = 0.299; 95% CI 0.174 – 0.514).
Conclusions
Patients with CNS metastases at MBC diagnosis represent 9% of this registry population. Poor baseline function and an increased risk of progression and death characterized these patients compared to those without baseline CNS metastases. Treatments administered to these patients differ from ASCO consensus recommendations (Ramakrishna, 2014). Further studies are needed to determine the associations between treatments and both clinical and patient-reported outcomes. At the time of presentation, detailed treatment data and additional patient-reported data will be available.
Citation Format: Cobleigh M, Hurvitz S, O'Shaughnessy J, Mason G, Yardley D, Jahanzeb M, Brufsky A, Rugo H, Swain S, Kaufman P, Tripathy D, Mayer M, Ogale S, Yoo B, Beattie M. Central nervous system metastases at diagnosis in patients with HER2+ MBC: Baseline characteristics, HER2-targeted treatments and clinical outcomes from the SystHERs registry. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P6-17-01.