State Key Laboratory of Oncology in South China, Guangzhou, China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, China; Medical Oncology Department, Sun Yat-Sen University Cancer Center, Guangzhou, China.
Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China.
Ann Oncol. 2018 Feb 1;29(2):452-458. doi: 10.1093/annonc/mdx698.
BACKGROUND: Co-administration of multiple antiemetics that inhibit several molecular pathways involved in emesis is required to optimize chemotherapy-induced nausea and vomiting (CINV) control in patients receiving highly emetogenic chemotherapy (HEC). NEPA, a fixed combination of a highly selective NK1 receptor antagonist, netupitant (300 mg), and the pharmacologically distinct 5-HT3RA, palonosetron (PALO 0.50 mg), has shown superior CINV prevention compared with PALO in cisplatin and anthracycline/cyclophosphamide-based settings. This study is the first head-to-head comparison of NEPA versus an aprepitant (APR)/granisetron (GRAN) regimen. PATIENTS AND METHODS: This randomized, double-blind phase III study conducted in Asia was designed with the primary objective to demonstrate non-inferiority of a single oral dose of NEPA compared with a 3-day oral APR/GRAN regimen in chemotherapy-naïve patients receiving cisplatin-based HEC. All patients also received oral dexamethasone (DEX) on days 1-4. The primary efficacy endpoint was complete response (CR: no emesis/no rescue medication) during the overall (0-120 h) phase. Non-inferiority was defined as a lower 95% CI greater than the non-inferiority margin set at - 10%. Secondary efficacy endpoints included no emesis, no rescue medication, and no significant nausea (NSN). RESULTS: Treatment groups were comparable for the 828 patients analyzed: predominantly male (71%); mean age 54.5 years; ECOG 0-1 (98%); lung cancer (58%). NEPA demonstrated non-inferiority to APR/GRAN for overall CR [NEPA 73.8% versus APR/GRAN 72.4%, 95% CI (-4.5%, 7.5%)]. No emesis [NEPA 75.0% versus APR/GRAN 74.0%, 95% CI (-4.8%, 6.9%)] and NSN rates [NEPA 75.7% versus APR/GRAN 70.4%, 95% CI (-0.6%, 11.4%)] were similar between groups, but significantly more NEPA patients did not take rescue medication [NEPA 96.6% versus APR/GRAN 93.5%, 95% CI (0.2%, 6.1%)]. NEPA was well tolerated with a similar safety profile to APR/GRAN. CONCLUSIONS: In this first study comparing NK1RA regimens and DEX, NEPA administered only on day 1 was non-inferior to a 3-day oral APR/GRAN regimen in preventing CINV associated with HEC.
背景：为了优化接受高致吐性化疗（HEC）的患者的化疗引起的恶心和呕吐（CINV）的控制，需要联合使用多种抑制呕吐相关分子途径的止吐药。NEPA 是一种高度选择性 NK1 受体拮抗剂奈妥吡坦（300mg）与药理学上不同的 5-HT3RA 帕洛诺司琼（PALO 0.50mg）的固定组合，与 PALO 相比，在顺铂和蒽环类药物/环磷酰胺为基础的方案中，显示出更好的 CINV 预防作用。本研究是首次对头对头比较 NEPA 与阿瑞匹坦（APR）/格拉司琼（GRAN）方案的研究。
患者和方法：这是一项在亚洲进行的随机、双盲 III 期研究，主要目的是证明与 3 天口服 APR/GRAN 方案相比，单剂量口服 NEPA 在接受顺铂为基础的 HEC 的化疗初治患者中的非劣效性。所有患者还在第 1-4 天接受了口服地塞米松（DEX）。主要疗效终点是在整个（0-120 小时）阶段的完全缓解（CR：无呕吐/无解救药物）。非劣效性定义为 95%置信区间（CI）下限大于设定的非劣效性边界为-10%。次要疗效终点包括无呕吐、无解救药物和无明显恶心（NSN）。
结果：对分析的 828 名患者进行治疗组之间具有可比性：主要为男性（71%）；平均年龄 54.5 岁；ECOG 0-1（98%）；肺癌（58%）。NEPA 对总体 CR 的非劣效性优于 APR/GRAN[NEPA 为 73.8%，而 APR/GRAN 为 72.4%，95%CI（-4.5%，7.5%）]。无呕吐[NEPA 为 75.0%，而 APR/GRAN 为 74.0%，95%CI（-4.8%，6.9%）]和 NSN 率[NEPA 为 75.7%，而 APR/GRAN 为 70.4%，95%CI（-0.6%，11.4%）]在两组之间相似，但明显更多的 NEPA 患者没有使用解救药物[NEPA 为 96.6%，而 APR/GRAN 为 93.5%，95%CI（0.2%，6.1%）]。NEPA 耐受性良好，安全性与 APR/GRAN 相似。
结论：在这项比较 NK1RA 方案和 DEX 的首次研究中，仅在第 1 天给予的 NEPA 在预防与 HEC 相关的 CINV 方面与 3 天口服 APR/GRAN 方案不劣效。
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