Abstract P4-10-08: Absolute lymphocyte count (ALC) is a predictor of eribulin benefit in advanced or metastatic breast cancer (MBC)

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Abstract Objective: This post hoc analysis assessed predictors for OS in patients (pts) treated with eribulin using data from 2 phase 3 studies: EMBRACE and Study 301. Background: Eribulin is a nontaxane synthetic inhibitor of microtubule dynamics approved for use in locally advanced or metastatic breast cancer after two previous lines of chemotherapy. In EMBRACE, 508 pts were randomized to eribulin monotherapy and 254 pts to the treatment of physician’s choice (TPC). Median OS of pts in the eribulin arm was significantly better than the TPC arm but no significant difference was seen in progression-free survival (PFS) by independent review. Study 301 randomized 554 pts to eribulin and 548 pts to capecitabine; no significant difference was seen in PFS. Kashiwagi et al, PloS one, 2017, suggested that cells such as tumor-infiltrating lymphocytes (TILs) in the tumor microenvironment may be a predictive marker of eribulin efficacy—pts with a high number of TILs had significantly longer PFS than pts with low TIL counts. Miyagawa et al, Clin Breast Cancer, 2018, found neutrophil-to-lymphocyte ratio to be significantly associated with longer PFS with eribulin. Our analysis focused on ALC, a peripheral immune parameter. Methods: Pts from EMBRACE with baseline ALCs were included in this analysis. The Kaplan-Meier method was used to estimate OS distribution. Interaction analysis of OS was performed between treatment and baseline ALCs to explore differential cutoff values. Hazard ratios (HR) were estimated from the stratified Cox proportional hazard model with the randomization stratification factors: HER2/neu status, prior capecitabine treatment, and geographical region. Multivariate analyses for baseline factors were performed using the Cox proportional hazard model to identify predictors and to confirm baseline ALC effect for OS. Similar methods were used to analyze associations between baseline ALC and OS in Study 301. Results: EMBRACE included 500 pts in the eribulin arm and 251 in the TPC arm with an evaluable baseline ALC. Pts with high baseline ALC consistently experienced greater eribulin benefit vs pts with low baseline ALC across cutoff values from 1300-1750/μL. The greatest difference was observed at the cutoff value of 1500/μL. Median OS was higher in pts with baseline ALC ≥1500/µL vs baseline ALC <1500/µL in the eribulin arm (15.6 vs 11.6 months) but not in the TPC arm (Table). The eribulin group showed prolonged OS compared with the TPC group in pts with ALC ≥1500/µL (HR 0.586; 95% CI: 0.437-0.784; P<0.001). There was no significant difference by treatment for ALC <1500/µL (HR 1.002; 95% CI: 0.800-1.253; P=0.989). Study 301 included 553 pts on eribulin and 547 pts on capecitabine. Similar results were observed in the eribulin arm, median OS was higher in pts with baseline ALC ≥1500/µL vs pts with baseline ALC <1500/µL (19.6 vs 14.6 months). There was a treatment effect favoring eribulin vs capecitabine at ALC ≥1500/µL but not at ALC <1500/µL. Conclusion: ALC at baseline may potentially be an independent predictor for longer OS in pts treated with eribulin. This hypothesis-generating study speculates that baseline ALC may be useful in the selection of pts to be treated with eribulin. Table. Multivariate analysis of OS identified the following predictors for OS in the eribulin group: prior capecitabine, ECOG PS, HR status, number of organs involved, refractory to taxanes, and baseline ALCStudyBaseline ALCArmPatients, nMedian OS (months)HR (95% CI)EMBRACEALC ≥1500/µLEribulin19915.60.586 (0.437-0.784)TPC9211.4ALC <1500/µLEribulin30111.61.002 (0.800-1.253)TPC15910.3Study 301ALC ≥1500/µLEribulin23319.60.811 (0.662-0.993)Capecitabine26916.0ALC <1500/µLEribulin32014.60.907 (0.758-1.084)Capecitabine27812.5ALC, absolute lymphocyte count; CI, confidence interval; HR, hazard ratio; OS, overall survival; TPC, treatment of physician’s choice. Citation Format: Javier Cortes, Jose Manuel Perez-Garcia, Kenichi Nomoto, Karenza Alexis, Kenichi Saito, Yuta Yoshimura, Kenzo Muramoto, Yasuo Miyoshi. Absolute lymphocyte count (ALC) is a predictor of eribulin benefit in advanced or metastatic breast cancer (MBC) [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P4-10-08.