Background: NEPA is an oral fixed-dose combination of netupitant, a new highly selective neurokinin-1 receptor\nantagonist, and palonosetron. This study was conducted to evaluate whether the efficacy of NEPA against\nchemotherapy-induced nausea and vomiting (CINV) in cycle 1 would be maintained over subsequent\nchemotherapy cycles in breast cancer patients receiving adjuvant anthracycline plus cyclophosphamide (AC). The\nstudy also describes the relationship between efficacy on day 1 through 5 (overall period) and control of CINV on\nday 6 through 21 (very late period) in each cycle.\nMethods: In this multicentre, phase II study, patients received both NEPA and dexamethasone (12 mg\nintravenously) just before chemotherapy. The primary efficacy endpoint was overall complete response (CR; no\nemesis and no rescue medication use) in cycle 1. Sustained efficacy was evaluated during the subsequent cycles by\ncalculating the rate of CR in cycles 2â??4 and by assessing the probability of sustained CR over multiple cycles. The\nimpact of both overall CR and risk factors for CINV on the control of very late events (vomiting and moderate-tosevere\nnausea) were also examined.\nResults: Of the 149 patients enrolled in the study, 139 were evaluable for a total of 552 cycles; 97.8% completed all\n4 cycles. The proportion of patients with an overall CR was 70.5% (90% CI, 64.1 to 76.9) in cycle 1, and this was\nmaintained in subsequent cycles. The cumulative percentage of patients with a sustained CR over 4 cycles was\n53%. NEPA was well tolerated across cycles. In each cycle, patients with CR experienced a significantly better\ncontrol of very late CINV events than those who experienced no CR. Among the patients with CR, the only\npredictor for increased likelihood of developing very late CINV was pre-chemotherapy (anticipatory) nausea\n(adjusted odds ratio = 0.65â??0.50 for no CINV events on cycles 3 and 4).\nConclusion: The high anti-emetic efficacy seen with the NEPA regimen in the first cycle was maintained over\nmultiple cycles of adjuvant AC for breast cancer. Preliminary evidence also suggests that patients achieving a CR\nduring the overall period gain high protection even against very late CINV events in each chemotherapy cycle.\nTrial registration: This trial was retrospectively registered at Clinicaltrials.gov identifier (NCT03862144) on 05/Mar/\n2019.
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