Validation of different personalized risk models of chemotherapy-induced nausea and vomiting: results of a randomized, double-blind, phase III trial of fosaprepitant for cancer patients treated with high-dose cisplatin.

Autor: Zhao Y; 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., Zhao B; Department of Day Ward, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, P. R. China., Chen G; 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., Chen Y; Department of Medical Oncology, Jiangxi Cancer Hospital, Nanchang, Jiangxi, P. R. China., Liao Z; Department of Medical Oncology, Shaanxi Provincial Cancer Hospital, Xi'an, Shaanxi, P. R. China., Zhang H; Department of Medical Oncology, The First People Hospital of Xiangtan, Xiangtan, Hunan, P. R. China., Feng W; Department of Medical Oncology, The First People Hospital of Foshan, Foshan, Guangdong, P. R. China., Li Y; Department of Medical Oncology, Shenyang Tenth People's Hospital, Shenyang, Liaoning, P. R. China., Weng H; Respiratory Medicine, Fuzhou Pulmonary Hospital of Fujian, Fuzhou, Fujian, P. R. China., Li W; Department of Medical Oncology, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, Guangdong, P. R. China., Zhou Y; Department of Medical Oncology, The Central Hospital of Lishui, Lishui, Zhejiang, P. R. China., Ren B; Department of Medical Oncology, Chongqing Three Gorges Central Hospital, Chongqing, P. R. China., Lu Y; Department of Medical Oncology, The First Affiliated Hospital of Hainan Medical University, Haikou, Hainan, P. R. China., Chen J; Department of Medical Oncology, Hunan Province Tumor Hospital, Changsha, Hunan, P. R. China., Liu Z; Institute of Materia Medica, Luoxin Pharmaceutical Group Co., Ltd, Shanghai, P. R. China., Su Z; Institute of Materia Medica, Luoxin Pharmaceutical Group Co., Ltd, Shanghai, P. R. China., Wang W; Institute of Materia Medica, Luoxin Pharmaceutical Group Co., Ltd, Shanghai, P. R. China., Zhang L; 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.
Jazyk: angličtina
Zdroj: Cancer communications (London, England) [Cancer Commun (Lond)] 2023 Feb; Vol. 43 (2), pp. 246-256. Date of Electronic Publication: 2022 Dec 22.
DOI: 10.1002/cac2.12397
Abstrakt: Background: 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.
Methods: 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).
Results: 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 2 ), 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).
Conclusions: 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.
(© 2022 The Authors. Cancer Communications published by John Wiley & Sons Australia, Ltd. on behalf of Sun Yat-sen University Cancer Center.)
Databáze: MEDLINE
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