Comparison of palonosetron with ondansetron, with respect to clinical efficacy and cost effectiveness in the prevention of chemotherapy induced nausea and vomiting in cancer patients
Health technology assessment
|Updated
Key message
Telemark hospital HE has asked for a comparison of palonosetron (Aloxi®) with other antiemetic substances in the class of serotonin antagonists, with respect to clinical efficacy and cost effectiveness in the prevention of chemotherapy induced nausea and vomiting in cancer patients.
We searched for systematic reviews (SR) and single studies with a randomized controlled design. The search regarding cost effectiveness studies was not limited in study design. We conducted a systematic review of the knowledge foundation. Two studies with medium quality matched the inclusion criteria. The quality of the reported outcomes was evaluated with GRADE.
Primary efficacy results:
- For patients who received chemotherapy with a moderate potential of inducing nausea and vomiting: Treatment with palonosetron probably yields more patients with no nausea or vomiting in the acute phase, than treatment with ondansetron.
- For patients who received chemotherapy with a high potential to induce nausea and vomiting: An approximately equal share of patients experienced no nausea and vomiting in the acute phase, regardless of whether they received ondansetron with additional dexamethasone or palonosetron with additional dexamethasone. The result seems to be the same for patients who received monotherapie with serotonin antagonists, but this conclusion is less robust, due to the low quality of the evidence for this outcome.
Safety:
There seems to be no difference in the safety profile of palonosetron and ondansetron. None of the studies reported serious side effects connected to either palonosetron or ondansetron.
Cost effectiveness:
According to our analysis, it seems unlikely that treatment with palonosetron can be considered cost effective compared to treatment with ondansetron, given the assumption that willingness to pay per quality adjusted life year is NOK 500 000.
Summary
Comparison of palonosetron with ondansetron with respect to clinical efficacy and cost effectiveness in the prevention of chemotherapy induced nausea and vomiting in cancer patients.
Background
Treatment with chemotherapy often leads patients to experience nausea and vomiting. In order to prevent these side effects, antiemetic drugs are frequently used. There are different groups of antiemetic drugs, one of which is called serotonin antagonists. Within this group, palonosetron (Aloxi®) is the newest and most expensive drug on the Norwegian market.
Telemark hospital HE has asked us to compare palonosetron with other drugs within this class, with respect to clinical efficacy and cost effectiveness. The purpose of this review is to conduct a methodological assessment of the current evidence regarding this question.
Methods
We preformed a systematic literature search in The Cochrane Library, Medline, EMBASSY, CHANTAL (Cumulative Index to Nursing and Allied Health Literature), CRD (Centre for Reviews and Dissemination databases), HEED (Health Economic Evaluation Database) and Clinical Evidence.
We searched for systematic reviews or single studies with a randomized controlled design (RCT). The search for economic evaluation studies was not limited in study design. Inputs for our own, model based economic evaluation were identified through hand searches of relevant databases. We included all studies where palonosetron was compared to ondansetron or tropisetron on a population of cancer patients receiving chemotherapy.
Two researchers selected studies and evaluated their overall quality based on a check list. We only included studies which were considered to have moderate or high quality. We used GRADE to assess the quality of the individual outcomes reported in the studies.
Results
We included two randomized controlled trials, one with 570 patients and the other with 673. Both of the RCTs compared 0.25 mg and 0.75 mg palonosetron with 32 mg ondansetron. Both serotonin antagonists were administered once only, intravenously 30 minutes before chemotherapy.
Primary efficacy results
- Regarding patients who received moderately emetogenic chemotherapy without addition of dexamethasone: In the acute phase, palonosetron most likely yields a larger proportion of patients with complete response than ondansetron, respectively 80.5 % vs. 66.8 %, RR=0.81, 95 % CI=1.07-1.36.
- Regarding patients who received highly emetogenic chemotherapy without addition of dexamethasone: It is possible that an equal proportion of patients will experience complete response in the acute phase, regardless of whether they are treated with palonosetron or ondansetron, respectively 46.7 % vs. 57.9 %, RR=0.81, 95% CI= 0.96-1.40.
- Regarding patients who received highly emetogenic chemotherapy with addition of dexamethasone: It is possible that an approximately equal proportion of patents will experience complete response in the acute phase, regardless of whether they are treated with palonosetron or ondansetron, respectively 64.7 % vs. 55.8 %, RR= 1.16, 95 % CI= 0.96-1.40.
Secondary efficacy results
For patients receiving moderately emetogenic chemotherapy:
Palonosetron is likely to yield a higher proportion of patients with complete response in the delayed phase than ondansetron. An approximately equal share of patients will be in need of rescue medication in the delayed and total phase.
For patients receiving highly emetogenic chemotherapy without addition of dexamethasone:
An approximately equal share of patients will achieve complete response in the delayed and total phase regardless of whether they are treated with palonosetron or ondansetron.
For patients’ receiving highly emetogenic chemotherapy with addition of dexamethasone:
Palonosetron is likely to yield a higher proportion of patients with complete response in the delayed phase; a higher proportion of patients with the outcome “no impact on their activities of daily life” due to nausea in the acute and delayed phase; due to vomiting in the delayed phase; and due to the combination of nausea and vomiting in the acute and delayed phase.
Safety results
An approximately equal share of patients will experience at least one side effect regardless of whether they are treated with palonosetron or ondansetron. None of the serious side effects were considered to be related to the serotonin antagonists.
Results from the economic evaluation
For patient who received moderately emetogenic chemotherapy, the additional costs of palonosetron compared to ondansetron is NOK 875 000 per quality adjusted life year (QALY) and NOK 3 000 per additional complete response over a period of five days.
For patients who received highly emetogenic chemotherapy with addition of dexamethasone, the additional cost of palonosetron compared to ondansetron is NOK 1 330 000 per QALY, NOK 4 000 per additional complete response.
For patients who receive highly emetogenic chemotherapy without addition of dexamethasone, treatment with ondansetron is cost saving compared to treatment with palonosetron.
The probabilistic sensitivity analysis (PSA) indicate that it is unlikely that treatment with palonosetron can be considered cost effective compared with treatment with ondansetron, given the assumption that willingness to pay per QALY is NOK 500 000.This conclusion is valid for all scenarios analyzed in this report.
Discussion
Results are based on two studies with medium quality. The two studies were based on two different populations. Both studies were designed to show non-inferiority. Twelve of the twenty reported outcomes have medium quality, the remaining were of low quality. None of the outcomes in the delayed phase were primary outcomes. The knowledge base regarding cost effectiveness is limited. The cost effectiveness results are highly dependent on the assumptions made. We chose to take this uncertainty into account by performing a probabilistic sensitivity analysis, where the uncertain parameters are assigned probability distributions.
Conclusion
For patients receiving moderately emetogenic chemotherapy palonosetron is likely to yield a higher proportion of patients with complete response in the acute, delayed and overall phase. For patients receiving highly emetogenic chemotherapy with additional dexamethasone, palonosetron is likely to yield a higher proportion of patients with complete response in the delayed and overall phase. For all other reported outcomes, except “activities of daily life”, palonosetron and ondansetron are likely to be equally efficacious.
The probabilistic sensitivity analysis (PSA) indicate that it is unlikely that palonosetron can be considered cost effective compared with treatment with ondansetron, given our assumption that willingness to pay per QALY is NOK 500 000.This conclusion is valid for all scenarios analyzed in this report.
Norwegian Knowledge Centre for the Health Services summarizes and disseminates evidence concerning the effect of treatments, methods, and interventions in health services, in addition to monitoring health service quality. Our goal is to support good decision making in order to provide patients in Norway with the best possible care. The Centre is organized under The Directorate for Health and Social Affairs, but is scientifically and professionally independent. The Centre has no authority to develop health policy or responsibility to implement policies.