Palonosetron compared with ondansetron in pediatric cancer patients: multicycle analysis of a randomized Phase III study

Abstract

aim:To investigate across multiple cycles the efficacy and safety of palonosetron in the prevention of chemotherapy-induced nausea and vomiting in pediatric cancer patients receiving highly or moderately emetogenic chemotherapy (HEC/MEC). Patients & methods: Patients were randomly assigned to 10, 20 μg/kg palonosetron or 3 × 150 μg/kg ondansetron for up to four cycles of HEC/MEC. Results: In all on-study chemotherapy cycles, complete response rates were higher in patients in the 20 μg/kg palonosetron group than the ondansetron group. Treatment-emergent adverse events were comparable between the palonosetron 20 μg/kg and ondansetron groups. conclusion: Over four cycles of HEC/ MEC, 20 μg/kg palonosetron was an efficacious and safe treatment for the prevention of chemotherapy-induced nausea and vomiting in pediatric cancer patients. Chemotherapy-induced nausea and vomiting (CINV) are common and distressing side effects in cancer patients receiving highly emetogenic chemotherapy (HEC) and moderately emetogenic chemotherapy (MEC) regimens [1,2]. CINV negatively impacts on patient quality of life [3], and can lead to medical complications and to noncompliance or premature discontinuation of anticancer therapy [4]. It is recognized that children receiving chemotherapy are more prone to vomiting than adults, and it is estimated that 70% of pediatric cancer patients receiving chemotherapy will develop CINV [2].Prevention of CINV in adult cancer patients receiving HEC or MEC regimens can be achieved through the use of antiemetic agents, a combination of a 5-hydroxytryptamine-3 (5-HT 3 ) receptor antagonist, a corticosteroid and a neurokinin-1 (NK 1 ) receptor antagonist is recommended [5][6][7]. While fewer studies of these agents have been performed in pediatric cancer patients than in adults, at the time of the study design, the combination of a 5-HT 3 receptor antagonist with a corticosteroid was recommended for pediatric patients receiving HEC or MEC chemotherapy regimens [2,5,6]. In later guidance from the Pediatric Oncology Group of Ontario (POGO), children scheduled to receive HEC are recommended to receive antiemetic prophylactic therapy of ondansetron or granisetron plus dexamethasone and aprepitant (≥12 years of age and receiving antineoplastic drugs not known to interact with aprepitant) or ondansetron or granisetron plus dexamethasone (<12 years of For reprint orders, please contact: reprints@futuremedicine.com

Palonosetron for Patients Undergoing High or Moderate Emetogenic Chemotherapy

“…The additional 12 included RCTs published in 14 reports comprised 7 open-label 22,23,[25][26][27]31,34 and 5 double-blind 24,[28][29][30]32,33,35 trials. Ten RCTs were parallel [22][23][24][25][27][28][29][30][32][33][34][35] and 2 were cross-over 26,31 in design. Sample size calculation was performed and reported in 9 RCTs.…”

“…[23][24][25]27,29,31,32,34,35 The efficacy results were analyzed using intention-to-treat approach in 2 RCTs 28,31 and per-protocol analysis or not was reported in the other 10 studies. [22][23][24][25][26][27]29,30,[32][33][34][35] Of the 5 included economic studies, 4 were cost-utility analysis 36,37,39,40 and 1 was a costeffectiveness analysis. 38 The cost-utility analysis by Botteman et al (2020) 36 was conducted using the efficacy data from a phase III noninferior RCT by Zhang et al (2018) 29 to determine the cost-effectiveness of NEPA relative to the granisetron-aprepitant regimen for HEC.…”

“…The detailed characteristics of the included SR 21 (Table 2), primary clinical studies (RCTs) [22][23][24][25][26][27][28][29][30][31][32][33][34][35] (Table 3), economic studies [36][37][38][39][40] (Table 4), and guidelines [41][42][43][44][45][46][47] (Table 5) are provided in Appendix 2.…”

“…The RCTs were conducted by authors in Egypt, 22 the Netherlands, 23 Japan, 24,26,31,35 India, 25,27 China, [28][29][30] Korea, 34 the US and multiple countries in Latin America, Western and Eastern Europe, and Russia. 32,33 Two RCTs were published in 2021, 22,23 1 in 2020, 24 2 in 2019, 25,26 3 in 2018, [27][28][29] and 4 in 2016. 31,32,34,35 Four RCTs were designed to test the noninferiority of palonosetron compared to ondansetron 23,27,32 or to granisetron.…”

“…34 There were 4 RCTs 25,27,28,32,33 involving pediatric patients with mean age ranging from 5 to 8 years and the proportion of females ranged between 28% to 52%. Two RCTs included patients naive to chemotherapy who were scheduled to receive HEC or MEC, 25,27 1 RCT included patients with or without previous chemotherapy who were scheduled to receive HEC or MEC, 32,33 and 1 RCT included patients with or without previous chemotherapy who were scheduled to receive HEC. 28 The types of cancer included both hematological cancer and solid tumour.…”