Date: 2014-10-23
Type of information: Presentation of results at a congress
phase: 3
Announcement: presentation of results at the International Society of Paediatric Oncology (SIOP) congress in Toronto, 22-24 October
Company: Helsinn (Switzerland)
Product: palonosetron HCl
Action
mechanism: Palonosetron (palonosetron hydrochloride) is a second generation 5-HT3 receptor antagonist developed for the prevention of CINV in patients with cancer.
Disease: chemotherapy-induced nausea and vomiting (CINV) in pediatric patients
Therapeutic area: Cancer - Oncology
Country:
Trial
details: The study was a Phase III, double-blind, double-dummy, randomized, parallel group stratified study of 502 patients randomized to treatment across 59 clinical centers, designed to show the non-inferiority of two dose levels of palonosetron (10 μg/kg and 20 μg/kg) compared with ondansetron (0.15 mg/kg every 4 hours/day for a maximum of 32mg/day), which is considered as standard therapy.
The primary objective of the trial was to demonstrate the non-inferiority of palonosetron to ondansetron, with a delta margin of -15%, in terms of complete response rates (no vomiting or recue medication) during the 24 hour period after chemotherapy administration (acute phase).
Secondary objectives included complete response rate at 25–120 hours and 0–120 hours after chemotherapy administration (delayed and overall phase respectively). The principal analysis population was the full analysis dataset (FAS) including 493 patients, aged from 64 days to 16.9 years. Of particular note, 45 patients were below age 2 years.
The patients were randomized to one of three groups: low-dose palonosetron (10 μg/kg; FAS n=166 patients), high-dose palonosetron (20 μg/kg; FAS n=165) and ondansetron (maximum dose 32mg/kg/day; FAS n=162).
Latest
news: * On October 23, 2014, Helsinn Group, the company focused on building quality cancer care, presented data at the International Society of Paediatric Oncology (SIOP) congress establishing that palonosetron, at a dose 20 μg/kg, is a valuable and efficacious treatment option for chemotherapy-induced nausea and vomiting (CINV) in pediatric patients up to 17 years of age. The data [presented at the SIOP congress in Toronto, 22-24 October] derive from a large randomized trial and establish that the investigated higher dose palonosetron (20 μg/kg), given as a single dose, demonstrated similar efficacy to multiple daily administrations of ondansetron up to 32mg/day (considered current standard of care) in the prevention of CINV in pediatric patients receiving highly emetogenic chemotherapy. The results also indicated that the 20 μg/kg dose of palonosetron does not require dose adjustment according to patient age. No safety concerns were raised by the study. Therefore, the study met its primary objective demonstrating the non-inferiority of palonosetron compared with ondansetron in pediatric patients up to 17 years of age. Considering the delayed phase, the complete response rate for palonosetron 20µg/kg was 38.8%, for ondansetron the complete response rate during this period was 28.9%. The pattern of results for complete response during the overall phase was consistent with that observed in the delayed phase rate for palonosetron 20µg/kg was 32.7%, and for ondansetron it was 24.1%. The type and frequency of treatment-emergent adverse events (TEAE) were consistent across the palonosetron 10 µg/kg and 20 µg/kg groups and the ondansetron group. No incremental toxicity was apparent in patients treated with the higher (20 µg/kg) palonosetron dose compared with those treated with the lower (10 µg/kg) dose. Throughout the study, no patients had drug-related TEAEs with fatal outcome or discontinued the study due to drug-related TEAEs. The safety profile of palonosetron in this pediatric study is consistent with the established information collected during previous clinical experiences. All withdrawals and/or deaths were unrelated to the study drug. In May 2014, the intravenous formulation of palonosetron was approved by the FDA for the prevention of acute nausea and vomiting associated with initial and repeat courses of emetogenic cancer chemotherapy in pediatric patients aged from one month up to 17 years. This was the first such approval of a product for patients under six months. The incidence of cancer in children peaks within the first year of life, so the approval increases the scope of treatment options to improve the quality of life for children undergoing cancer chemotherapy.
The complete response rate (95% CI) during the acute phase was 54.2% (46.3%–61.9%) and 59.4% (51.5%–66.9%) for the low- and high-dose palonosetron groups, respectively, and 58.6% (50.6%–66.2%) in the ondansetron group. This confirmed the non-inferiority between the high-dose 20 μg/kg of palonosetron and ondansetron. The pharmacokinetic profile of palonosetron after a 15 minute infusion was comparable for all age groups and for both dose levels confirming no need for dose adjustment according to patient age.
