e12594 Background: Anthracycline and Taxane have been widely used and studied in neoadjuvant setting for treatment of locally advanced breast cancer. Various regimens have explored the addition of newer agents to determine safety and efficacy, and pathological complete response(pCR) has been demonstrated to be associated with favorable overall survival in primary breast cancer. Pertuzumab increases the rate of pathological complete response in the preoperative context and increases overall survival among patients with metastatic disease when it is added to Trastuzumab and chemotherapy for the treatment of human epidermal growth factor receptor 2 (Her2)-positive breast cancer. In addition, APHINITY trial showed that Pertuzumab significantly improved the rates of invasive-disease-free survival among patients with HER2-positive, operable breast cancer when it was added to Tastuzumab and chemotherapy. We conducted a clinical phase II neoadjuvant trial of nab-Paclitaxel, Trastuzumab and Pertuzumab followed by Anthracycline Based Regimens in Patients with Operable Her2 Positive Breast Cancer. Methods: The study is designed to evaluate nab-paclitaxel, Trastuzumab and Pertuzumab followed by EC or AC or FEC as neoadjuvant therapy in patients with Her2 positive operable breast cancer. Patients are treated with neoadjuvant nab-paclitaxel(260 mg/m2 ), Trastuzumab and Pertuzumab followed by EC(Epirubicin 90 mg/m2 , Cyclophosphamide 600 mg/m2) or AC(Doxorubicin 60 mg/m2 , Cyclophosphamide 600 mg/m2) or FEC(Fluorouracil 500mg/m2, Epirubicin 100 mg/m2 , Cyclophosphamide 500 mg/m2 ) q21d x 4. Patients undergo surgery 4-6 weeks later from completing chemotherapy. The primary endpoint, pCR is defined as no evidence of invasive tumors in the final surgical sample both in the breast and axillary lymph nodes. Secondary endpoints include overall response rate, disease-free survival, rate of breast conserving surgery, histological response rate, rate of sensory neuropathy ant the safety of the treatment. Results: In 30 evaluable patients, the pCR rate was 50%; 6/19 (31.6%) in ER-positive and 9/11 (81.8%) in ER-negative, 1/7 (14.3%) in IHC 2+, FISH positive and 14/23 (60.9%) in IHC 3+ . Of the study treatments, the most frequent reason for delay or dose reduction was hematologic toxicity; no patient required a dose reduction for nab-PTX because of peripheral neuropathy. Conclusions: Neoadjuvant treatment using albumin-bound Paclitaxel, Trastuzumab and Pertuzumab followed by Anthracycline based regimens appears to be effective especially in pure HER2 type or IHC 3+ cases.

Purpose: While the absolute lymphocyte count (ALC) and neutrophil-to-lymphocyte ratio (NLR) are associated with prolonged progression-free survival (PFS) and overall survival (OS), the influence of previous chemotherapy on blood cell counts may necessitate an evaluation of baseline ALC and NLR in patients receiving first-line chemotherapy. Methods: Patients with human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (MBC) who received first-line eribulin chemotherapy in two phase 2 trials (BIRICHEN and OMC-BC 03) were retrospectively analyzed. HER2-negative MBC patients who received first-line chemotherapy other than eribulin (treatment of physician’s choice; TPC) at the Osaka Medical and Pharmaceutical University Hospital between March 2013 and March 2017 were also analyzed for comparison. Results: In the eribulin group, the median OS (mOS) was 30.9 and 17.8 months in the high-(H-)ALC (≥1500/μL; n=33) and low-(L-)ALC (<1500/μL; n=26) groups, respectively (hazard ratio [HR], 0.52; 95% confidence interval [CI]: 0.27-1.01), whereas it was 30.9 months and 15.4 months in the L-NLR (<2.5; n=23) and H-NLR (≥2.5; n = 36) groups, respectively (HR, 0.49; 95% CI: 0.25-0.95). In the TPC group, neither ALC nor NLR was associated with OS or PFS extension. After propensity-score matching, the mOS in the eribulin group was 32.0 and 19.6 months, respectively, in the H- and L-ALC groups (HR, 0.43; 95% CI: 0.18-0.99), while OS in the L- and H-NLR groups showed no significant differences in the eribulin group (HR, 0.65; 95% CI: 0.27-1.58). Conclusions: ALC is a prognostic marker for first-line eribulin chemotherapy, but not for other agents.

Background: Eribulin demonstrated improving overall survival of HER2-negative metastatic breast cancer in EMBRACE trial. Recently, ad hoc analysis of the trial showed that immune response markers such as absolute lymphocyte count (ALC) was associated with prognosis. However, blood cell count must be influenced by previous chemotherapy because the trial was targeted for late-line treatment.Previously we had conducted two phase 2 trials that estimated efficacy of eribulin as the first-lien chemotherapy for HER2-negative metastatic breast cancer in Japan. Base line ALC and NLR were examined for the participants of these trials to determine whether they were also associated with prognosis in the first-line setting. Patients and Methods: A total of 59 patients were enrolled this study including 35 patients of BIRICHEN trial (UMIN000006086; SpringerPlus 2016;5:164) for only first-line chemotherapy with eribulin and 24 patients who treated as the first-line chemotherapy in OMC-BC03 trial targeted for first and second line chemotherapy (UMIN000009568; Cancer Chemother Pharmacol 2018; 81:923). Pretreatment blood cell counts were collected from case report form and compared with survival data. Cutoff value of ALC was set at 1500/mm3 and that of NLR was set at 3 in accordance with ad hoc analysis of EMBRACE trial. The ethics committees of Osaka Medical College and Osaka City University approved the present study. Results: Median value of ALC was 1690/mm3(Quartile Q1,Q3: 1014, 2012) and that of NLR was 2.17(Q1,Q3: 1.54, 2.99). In comparison with ALC, overall survival (OS) was 132.6 months in the ALC-high group(&gt;=1500;n=33) versus 76.4 months in the ALC-low group (&lt; 1500; n=26). Hazard ratio(HR) was 0.52(95%CI; 0.27-1.01) with border line significancy. Progression free survival(PFS) is 28.0 months in the ALC-high group versus 20.4 months in the ALC-low group. HR was 0.91(95% CI; 0,51-1.60) without statistically significant difference. In NLR, OS was 20.7 months in the NLR-low group(&lt;3;n=45) versus 4.6 months in the NLR-high group. HR was 0.40 (95%CI; 018-0.90) with statistical significance. PFS was 6.2 months in the NLR-low group versus 10.8 months in the NLR-high group (&gt;=3; n=14). HR was 0.57 (95%CI; 0.25-1.30) without statistically significant difference. Conclusions: In the post hoc analysis of the EMBRACE trial, patients who assigned eribulin group with ALC 1500 or higher had better OS than those with ALC less than 1500, but no difference was observed in PFS. In addition, those with NLR less than 3 had better PFS and OS than those with NLR 3 or more. In comparison with the capecitabine group, although low NLR was a good prognostic factor not only in eribulin group but also in capecitabine group, high ALC was suggested to be a particular prognostic factor of eribulin. However, since EMBRACE study was a late line setting, there could be an effect of myelosuppression by pretreatment. Our first-line results did not affect bone marrow function by prior chemotherapy, but similar results were obtained. ALC may be a prognostic factor of eribulin regardless of the treatment line, suggesting that eribulin exerts its effect by acting on the immune microenvironment. Citation Format: Tsutomu Takashima, Kosei Kimura, Hidemi Kawajiri, Shinichiro Kashiwagi, Shinya Tokunaga, Shigehiko Nishimura, Satoru Noda, Hiroyo Oku, Ayana Ikari, Tomo Tominaga, Saki Maezawa, Junna Sakane, Mitsuhiko Iwamoto. High absolute lymphocyte counts are associated with longer overall survival in patients with metastatic breast cancer treated with eribulin as the first-line chemotherpy. Combined analysis of two phase 2 study [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P4-05-06.