Abstract P2-09-31: Predictive impact of absolute lymphocyte counts for progression-free survival in HER2-positive advanced breast cancer treated with pertuzumab and trastuzumab plus eribulin or nab-paclitaxel

Abstract

Background: Tumor-infiltrating lymphocytes might be a one of predictive outcome of human epidermal growth factor receptor 2 (HER2)-positive advanced breast cancer (ABC) patients (pts) who treated with trastuzumab and pertuzumab (TP) plus docetaxel. Although peripheral blood-based parameter (PBBP) is reported as a prognostic indicator of patients with early breast cancers, utility of PBBP has not been studied in HER2-positive ABC. Objective:The aim of our study was to determine whether PBBP is significant for predictive efficacy in HER2-positive ABC treated with TP combined with eribulin (ERI) or nab-paclitaxel (Nab-PTX). Methods: The 51 patients' data from two single arm phase II trials was included in this retrospective-prospective study; ERI + TP (n=30) or Nab-PTX + TP (n=21) registered with UMIN000012375 or UMIN000006838, respectively. We assessed the PBBP in prospectively collected data and investigated their association with progression-free survival (PFS). In consideration of PBBP, we evaluated absolute lymphocyte count (ALC), neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR). The cutoff values of ALC, NLR, and PLR were set at 1000 cells/μL, 2, and 250, respectively. Results:Median age at baseline was 58 years (range: 31-77). Median number of previous chemotherapy was 3 (range: 1-10). Pts had multiple metastases, 53% with LNs, 35% with bone, 25% with lung, 20% with liver, and 6% with brain. The objective response rate (CR+PR) and clinical benefit rate (CR+PR+ more than 6 month SD) were 37% (n=19) and 59% (n=30), respectively. The median PFS of all pts was 301 days (range: 21-1281). The PFS of pts with ALC-High was significantly better than those of ALC-low (hazard ratio (HR): 2.74, 95% confidence interval (CI): 1.28 to 5.86; p= .0097). Furthermore, improved PFS was obtained in pts with ALC greater than 1500 cells/μL compared with less than 1000 cells/uL (HR: 4.05, 95% CI: 1.60 to 11.6; p= .0029). Significant associations seem to exist irrespective of number of previous chemotherapy. Since we combined different studies for evaluating PBBP, ERI and Nab-PTX were calculated separately. Marginally significant associations between ALC and PFS were obtained both in ERI (HR: 2.18, 95% CI: 0.87 to 5.60; p=.0973) and Nab-PTX (HR: 3.26, 95% CI: 0.80 to 12.4; p=.0939). The PFS of NLR-low pts was significantly better than those of NLR-high (HR: 2.29, 95% CI: 1.01 to 5.90; p= .0477), but this statistical difference was inferior to those of ALC. There was no significant association between PLR and PFS. Conclusions: Pre-treatment ALC-High was significantly correlated with favorable PFS of pts treated with TP irrespective of combination chemotherapy in HER2-positve ABC. Prolonged PFS of TP combination therapy might be obtained mediating through host systemic onco-immunity. These data obtained here suggest that a usefulness of ALC for selecting pts who might have clinical benefit from TP combination therapy for heavily treated HER2-positve ABC. Citation Format: Araki K, Ito Y, Fukada I, Kobayashi K, Ohno S, Miyagawa Y, Imamura M, Kira A, Takatsuka Y, Egawa C, Suwa H, Miyoshi Y. Predictive impact of absolute lymphocyte counts for progression-free survival in HER2-positive advanced breast cancer treated with pertuzumab and trastuzumab plus eribulin or nab-paclitaxel [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 P2-09-31.

A maintained absolute lymphocyte count predicts the overall survival benefit from eribulin therapy, including eribulin re-administration, in HER2-negative advanced breast cancer patients: a single-institutional experience

“…lymphopenia as an adverse prognostic factor) in patients with ABC or other advanced malignancies [22][23][24]. Indeed, to our knowledge, there is only one report from Araki et al [25] that described a significant association between a maintained ALC (≥1500/μL) and the PFS of anti-HER2 therapy in HER2+ ABC patients receiving eribulin or nab-paclitaxel combined with trastuzumab and pertuzumab. According to our present study, an ALC of ≥1000/μL was an independent hematologic parameter influencing the OS in the ER+ subgroup, but not in the ER-subgroup.…”