Background: Breast cancer (BC) patients receiving anthracycline-cyclophosphamide (AC) chemotherapy (CT) are at risk for developing CINV due not only to the emetogenicity of the CT but also to young age and gender. As recommended by international antiemetic guidelines, targeting multiple molecular pathways involved in emesis related to AC is important for maximizing control of CINV and improving the functional status of BC patients during CT. NEPA is a fixed-dose combination of netupitant (NETU), a highly-selective NK1 receptor antagonist (RA), and palonosetron (PALO), a pharmacologically distinct 5-HT3 RA, that targets dual antiemetic pathways with a convenient single day dose. Methods: This was a multinational, randomized, double-blind, phase 3 study evaluating the efficacy and safety of a single oral dose of NEPA (NETU 300 mg + PALO 0.50 mg) versus a single oral 0.50 mg dose of PALO in chemotherapy-naïve patients receiving AC. All patients received oral dexamethasone (DEX) on day 1 (12 mg NEPA arm; 20 mg PALO arm). The primary efficacy endpoint was complete response (CR: no emesis, no rescue medication) in the delayed phase, 25-120h after CT. The Functional Living Index-Emesis (FLIE) questionnaire with a 5-day recall period was used to assess the impact of CINV on patients’ daily lives as a secondary endpoint. The FLIE consists of 9 nausea-specific (nausea domain) and 9 vomiting-specific (vomiting domain) items that address the effect of nausea and vomiting on daily life. Each item is scored on a 7-point 100 mm visual analog scale with anchors of “none/not at all” and “a great deal”. The proportion of patients with an average item score >6 reflecting “no impact on daily life” (NIDL) (ie, total FLIE score >108, nausea/vomiting domain score >54) was compared for NEPA vs PALO using a Cochran-Maentel-Haenszel test stratified by age class and region. Results: 1455 patients with a mean age of 54 were randomized to receive NEPA or PALO. Treatment groups were similar; 98% were females with BC (97%). As previously reported (ASCO 2013), NEPA showed superior CR rates compared to PALO for the acute 0-24h (88% vs 85%; p = 0.047), delayed (77% vs 70%; p = 0.001) and overall 0-120h (74% vs 67%; p = 0.001) phases. A greater proportion of NEPA-treated patients reported NIDL for nausea, vomiting and combined domains compared to PALO. % Patients with NIDL (Overall 0-120h)NEPA (N = 724)PALO (N = 725)p-valueNausea domain72%66%0.015Vomiting domain90%84%0.001Overall combined79%72%0.0056 patients excluded who did not receive AC or study drug The adverse event (AE) profile was comparable between groups. Most frequently reported treatment-related AEs for NEPA and PALO, respectively, were headache (3.3%, 3.0%) and constipation (2.1%, 2.1%). Conclusions: In this large Phase 3 study of predominantly females with BC receiving AC, NEPA was superior to PALO in preventing CINV and reducing the negative impact of CINV on patients’ daily lives. As a fixed-dose antiemetic drug combination including an NK1 RA and 5-HT3 RA, NEPA offers improved efficacy over PALO alone, with a convenient single-day dose, and oral DEX only on day 1. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P3-09-01.

Background: Single-agent chemotherapy (CT) is the standard treatment option in endocrine receptor (ER)-positive advanced breast cancer (ABC) after failure of endocrine therapy (ET) or in patients (pts) without visceral crisis. Both weekly paclitaxel (WP) and oral vinorelbine (OV) are among the recommended treatment options in this setting. The aim of this study was to evaluate the efficacy and safety profiles of OV and WP in a face to face study. Material and methods: Pts with ER-positive, HER2-negative ABC, with an age ≥18 years and with a documented locally recurrent or metastatic involvement previously untreated by CT were eligible. Pts were randomized to receive, as first-line CT, 3 weekly-cycles of either: ARM A: weekly OV, given as a 80 mg/m2 dose (following a first cycle at 60 mg/m2, dose escalation to 80 in the absence of grade 3 or 4 toxicity at cycle 1); ARM B: WP 80 mg/m2 per week. Primary endpoint was disease control rate (DCR). Pts were stratified according to prior taxane CT and visceral metastases. Results: 131 pts have been treated (OV: 66, WP: 65). Baseline pts characteristics (Arms OV/WP): median age 58/61 years; median number of prior ET: 2/2; prior (neo) adjuvant CT 74/72%; prior anthracycline 67/62%; prior taxane: 41/42%; >3 metastatic sites 42/48%; visceral metastases 79/79%. Median number of cycles (range): 6(1-55)/7(1-44); dose escalation of OV was performed in 75% of pts. Safety: most common non-hematological related G3/4 adverse events per pt were fatigue 8/2%, peripheral neuropathy 0/5%, nausea 3/0%, diarrhoea 3/2%, vomiting 3/0%, constipation 3/2%, alopecia (G2) 2/34%, no toxic deaths; febrile neutropenia was present in 2/0% of pts. Quality of life: over time, no major differences between both arms have been observed. Efficacy: DCR in the intent-to-treat population was [95%CI] 75.8 [63.6-85.5] /75.4 [63.1-85.2]%; overall response rate 20/40%; median progression-free survival: 5.5/6.4 months. Median overall survival was: OV 27.6/WP 22.3 months. Conclusion: Both OV and WP reached similar DCR rates of 75%. Each regimen presented a specific tolerance profile, with, in particular, a lower incidence of alopecia and peripheral neuropathy with OV. OV and WP are valid first-line CT options for ER-positive/HER2-negative pts with ABC. Citation Format: Aapro MS, Hegg R, Ruiz Borrego M, Staroslawska E, Morales S, Cinieri S, De Freitas Junior R, Garcia Estevez L, Szombara E, Hervieu H, Groc M, Villanova GR. Final results of NorBreast-231, a randomized phase II study evaluating weekly oral vinorelbine versus weekly paclitaxel as first-line chemotherapy in patients with advanced breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-14-01.

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