NEPA is an oral fixed-dose combination of netupitant, a new highly selective neurokinin-1 receptor antagonist, and palonosetron. This study was conducted to evaluate whether the efficacy of NEPA against chemotherapy-induced nausea and vomiting (CINV) in cycle 1 would be maintained over subsequent chemotherapy cycles in breast cancer patients receiving adjuvant anthracycline plus cyclophosphamide (AC). The study also describes the relationship between efficacy on day 1 through 5 (overall period) and control of CINV on day 6 through 21 (very late period) in each cycle. In this multicentre, phase II study, patients received both NEPA and dexamethasone (12 mg intravenously) just before chemotherapy. The primary efficacy endpoint was overall complete response (CR; no emesis and no rescue medication use) in cycle 1. Sustained efficacy was evaluated during the subsequent cycles by calculating the rate of CR in cycles 2–4 and by assessing the probability of sustained CR over multiple cycles. The impact of both overall CR and risk factors for CINV on the control of very late events (vomiting and moderate-to-severe nausea) were also examined. Of the 149 patients enrolled in the study, 139 were evaluable for a total of 552 cycles; 97.8% completed all 4 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 maintained in subsequent cycles. The cumulative percentage of patients with a sustained CR over 4 cycles was 53%. NEPA was well tolerated across cycles. In each cycle, patients with CR experienced a significantly better control of very late CINV events than those who experienced no CR. Among the patients with CR, the only predictor for increased likelihood of developing very late CINV was pre-chemotherapy (anticipatory) nausea (adjusted odds ratio = 0.65–0.50 for no CINV events on cycles 3 and 4). The high anti-emetic efficacy seen with the NEPA regimen in the first cycle was maintained over multiple cycles of adjuvant AC for breast cancer. Preliminary evidence also suggests that patients achieving a CR during the overall period gain high protection even against very late CINV events in each chemotherapy cycle. This trial was retrospectively registered at Clinicaltrials.gov identifier (NCT03862144) on 05/Mar/2019.

中文翻译：

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Netupitant /帕洛诺司琼（NEPA）和地塞米松预防接受辅助蒽环类药物加环磷酰胺治疗的乳腺癌患者的呕吐：一项多周期，II期研究。

NEPA是netupitant，新型高选择性神经激肽1受体拮抗剂和palonosetron的口服固定剂量组合。这项研究的目的是评估在接受辅助蒽环类抗生素加环磷酰胺（AC）治疗的乳腺癌患者中，在随后的化疗周期中，能否保持NEPA在第1周期中对抗化疗引起的恶心和呕吐（CINV）的功效。该研究还描述了每个周期中第1天至第5天（整个时期）的疗效与第6天至第21天CINV控制（非常晚的时期）之间的关系。在这项多中心，II期研究中，患者在化疗前同时接受了NEPA和地塞米松（静脉注射12 mg）。主要功效终点为第1周期的总体完全缓解（CR；无呕吐，无急救药物的使用）。在随后的循环中，通过计算2–4循环中CR的发生率并评估多个循环中持续CR的可能性，来评估持续疗效。还检查了CINV的总体CR和危险因素对极晚事件（呕吐和中度至重度恶心）控制的影响。在该研究的149名患者中，有139名可评估，共进行552个周期。97.8％完成了所有4个周期。在第1周期中，总体CR的患者比例为70.5％（90％CI，64.1至76.9），并在随后的周期中保持这一比例。持续CR超过4个周期的患者的累积百分比为53％。NEPA在各个周期中耐受性良好。在每个周期中，CR患者比未经历CR的患者对晚期CINV事件的控制明显更好。在CR患者中，发生CINV晚期的可能性增加的唯一预测因素是化疗前（预期的）恶心（第3和第4周期无CINV事件的校正比值比= 0.65-0.50）。在乳腺癌的佐剂AC的多个周期中，通过NEPA方案在第一周期中观察到的高止吐功效得以维持。初步证据还表明，即使在每个化疗周期中发生非常晚的CINV事件，在整个疗程中均达到CR的患者也可以获得较高的保护。该试验已于2019年3月5日在Clinicaltrials.gov标识符（NCT03862144）进行了追溯注册。在乳腺癌的佐剂AC的多个周期中，通过NEPA方案在第一周期中观察到的高止吐功效得以维持。初步证据还表明，即使在每个化疗周期中发生非常晚的CINV事件，在整个疗程中均达到CR的患者也可以获得较高的保护。该试验已于2019年3月5日在Clinicaltrials.gov标识符（NCT03862144）进行了追溯注册。在乳腺癌的佐剂AC的多个周期中，通过NEPA方案在第一周期中观察到的高止吐功效得以维持。初步证据还表明，即使在每个化疗周期中发生非常晚的CINV事件，在整个疗程中均达到CR的患者也可以获得较高的保护。该试验已于2019年3月5日在Clinicaltrials.gov标识符（NCT03862144）进行了追溯注册。