Navari Rudolph M, Bonizzoni Erminio
World Health Organization, Mount Olive, Alabama, USA.
RIDE2Med Foundation, Milan, Italy.
Cancer Med. 2025 Apr;14(7):e70549. doi: 10.1002/cam4.70549.
Although control of chemotherapy-induced nausea and vomiting (CINV) is substantially improved with guideline-directed antiemetic prophylaxis, breakthrough CINV remains a significant clinical patient problem. In subsequent cycles after breakthrough occurs, antiemetic guidelines recommend adding agents not used in the initial cycle. This study was designed to evaluate the use of NEPA (netupitant/palonosetron) plus dexamethasone with or without olanzapine for the prevention of CINV in the second cycle of chemotherapy for patients receiving highly (HEC) or moderately emetogenic chemotherapy (MEC) who developed breakthrough CINV in their first cycle despite guideline-directed prophylactic antiemetics.
This was a Phase 2, single center, open-label study. Patients received guideline-recommended prophylactic antiemetics in Cycle 1 based on the chemotherapy emetogenicity. Patients who experienced breakthrough CINV in Cycle 1 received intravenous (IV) NEPA (Day 1) plus dexamethasone (Days 1-4) and olanzapine (Days 1-4) for HEC or IV NEPA (Day 1) plus dexamethasone (Days 1-4) for MEC in Cycle 2.
Of the 227 patients enrolled in Cycle 1, 100 patients (n = 37 HEC, 63 MEC) experienced breakthrough CINV and received the NEPA-based treatments in Cycle 2. The complete response (no emesis/no rescue use) rates [95% confidence intervals] during the overall (0-120 h) phase were 76% [59%, 88%] and 79% [67%, 89%] in the HEC and MEC groups, respectively.
These results show that NEPA with or without olanzapine is an effective approach for CINV prevention for patients receiving HEC or MEC who develop breakthrough CINV after their first course of chemotherapy. The results support the antiemetic guideline recommendations.
clinicaltrials.gov identifier: NCT06065722.
尽管通过指南指导的止吐预防措施，化疗引起的恶心和呕吐（CINV）的控制有了显著改善，但突破性CINV仍然是一个严重的临床患者问题。在突破性CINV发生后的后续周期中，止吐指南建议添加在初始周期中未使用的药物。本研究旨在评估NEPA（奈妥匹坦/帕洛诺司琼）联合地塞米松加或不加奥氮平，用于预防在第一个周期中尽管接受了指南指导的预防性止吐药物治疗仍发生突破性CINV的接受高致吐性化疗（HEC）或中度致吐性化疗（MEC）的患者在第二个化疗周期中的CINV。
这是一项2期、单中心、开放标签研究。患者在第1周期根据化疗致吐性接受指南推荐的预防性止吐药物。在第1周期经历突破性CINV的患者在第2周期接受静脉注射（IV）NEPA（第1天）加地塞米松（第1 - 4天）以及奥氮平（第1 - 4天）用于HEC，或静脉注射NEPA（第1天）加地塞米松（第1 - 4天）用于MEC。
在第1周期入组的227例患者中，100例患者（n = 37例HEC，63例MEC）经历了突破性CINV并在第2周期接受了基于NEPA的治疗。在整个（0 - 120小时）阶段，HEC组和MEC组的完全缓解率（无呕吐/未使用救援药物）[95%置信区间]分别为76%[59%，88%]和79%[67%，89%]。
这些结果表明，对于在第一个化疗疗程后发生突破性CINV的接受HEC或MEC的患者，使用或不使用奥氮平的NEPA是预防CINV的有效方法。这些结果支持止吐指南的建议。
clinicaltrials.gov标识符：NCT06065722。
