Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, P. R. China.
Department of Day Ward, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, P. R. China.
Cancer Commun (Lond). 2023 Feb;43(2):246-256. doi: 10.1002/cac2.12397. Epub 2022 Dec 22.
Highly emetogenic chemotherapy induces emesis in cancer patients without prophylaxis. The purpose of this study was to evaluate the efficacy and safety of a fosaprepitant-based triple antiemetic regimen for the prevention of chemotherapy-induced nausea and vomiting (CINV) in patients with solid malignant tumors, determine risk factors and externally validate different personalized risk models for CINV.
This phase III trial was designed to test the non-inferiority of fosaprepitant toward aprepitant in cancer patients who were to receive the first cycle of single-day cisplatin chemotherapy. The primary endpoint was complete response (CR) during the overall phase (OP) with a non-inferiority margin of 10.0%. Logistic regression models were used to assess the risk factors of CR and no nausea. To validate the personalized risk models, the accuracy of the risk scoring systems was determined by measuring the specificity, sensitivity and area under the receiver operating characteristic (ROC) curve (AUC), while the predictive accuracy of the nomogram was measured using concordance index (C-index).
A total of 720 patients were randomly assigned. CR during the OP in the fosaprepitant group was not inferior to that in the aprepitant group (78.1% vs. 77.7%, P = 0.765) with a between-group difference of 0.4% (95% CI, -5.7% to 6.6%). Female sex, higher cisplatin dose (≥ 70 mg/m ), no history of drinking and larger body surface area (BSA) were significantly associated with nausea. The AUC for the acute and delayed CINV risk indexes was 0.68 (95% CI: 0.66-0.71) and 0.66 (95% CI: 0.61-0.70), respectively, and the C-index for nomogram CINV prediction was 0.59 (95% CI, 0.54-0.64). Using appropriate cutoff points, the three models could stratify patients with high- or low-risk CINV. No nausea and CR rate were significantly higher in the low-risk group than in the high-risk group (P < 0.001).
Fosaprepitant-based triple prophylaxis demonstrated non-inferior control for preventing CINV in patients treated with cisplatin-base chemotherapy. Female cancer patients without a history of alcohol consumption, with larger BSA and received high-dose cisplatin might be more vulnerable to CINV. Three personalized prediction models were well-validated and could be used to optimize antiemetic therapy for individual patients.
高致吐性化疗在没有预防措施的情况下会引起癌症患者的呕吐。本研究的目的是评估基于福沙吡坦的三联止吐方案预防实体恶性肿瘤患者化疗引起的恶心和呕吐（CINV）的疗效和安全性，确定 CINV 的风险因素，并对外验证不同的个体化风险模型。
这项 III 期试验旨在测试福沙吡坦与阿瑞匹坦相比在接受单天顺铂化疗的癌症患者中的非劣效性。主要终点是整个阶段（OP）的完全缓解（CR），非劣效性边界为 10.0%。使用逻辑回归模型评估 CR 和无恶心的风险因素。为了验证个体化风险模型，通过测量特异性、敏感性和接收者操作特征（ROC）曲线下的面积（AUC）来确定风险评分系统的准确性，而通过一致性指数（C-index）来测量列线图的预测准确性。
共有 720 名患者被随机分配。福沙吡坦组的 OP 期间的 CR 不劣于阿瑞匹坦组（78.1%对 77.7%，P=0.765），两组之间的差异为 0.4%（95%CI，-5.7%至 6.6%）。女性、较高的顺铂剂量（≥70mg/m ）、无饮酒史和较大的体表面积（BSA）与恶心显著相关。急性和迟发性 CINV 风险指数的 AUC 分别为 0.68（95%CI：0.66-0.71）和 0.66（95%CI：0.61-0.70），列线图 CINV 预测的 C-index 为 0.59（95%CI，0.54-0.64）。使用适当的截断点，这三个模型可以对具有高或低 CINV 风险的患者进行分层。低风险组的无恶心和 CR 率明显高于高风险组（P<0.001）。
基于福沙吡坦的三联预防方案在接受顺铂为基础的化疗的患者中显示出对 CINV 的非劣效控制。无饮酒史、BSA 较大和接受高剂量顺铂的女性癌症患者可能更容易发生 CINV。三个个体化预测模型得到了很好的验证，可以用于优化个体患者的止吐治疗。
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