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Efficacy of olanzapine, neurokinin-1 receptor antagonists, and thalidomide in combination with palonosetron plus dexamethasone in preventing highly emetogenic chemotherapy-induced nausea and vomiting: a Bayesian network meta-analysis

Abstract

Background

Olanzapine, neurokinin-1-receptor-antagonists (NK-1-RA), and thalidomide added to palonosetron + dexamethasone (PALO-DEX) have been evaluated in separate studies as prophylaxis for chemotherapy-induced nausea and vomiting (CINV) due to highly emetogenic chemotherapy (HEC). We conducted a Bayesian network meta-analysis to compare the prophylactic efficacy of these agents in combination with PALO-DEX.

Methods

PubMed, Medline/Ovid, Embase, and Clinicaltrials.gov were searched from inception through 22 Mar 2018. Study quality was assessed using the Cochrane methodology. A Bayesian network meta-analysis using random-effects models was used to asses complete response (CR) and rate of no nausea (RNN) in acute, delayed, and overall phases and were expressed as odds ratios (OR) and 95% credible interval (95% CrI). Ranking probabilities of treatments were calculated using the surface under the cumulative ranking curve (SUCRA) to identify the probability of a given treatment as the best option against the worst option.

Results

Nine RCTs involving two thousand nine hundred fifty-nine patients were included. The olanzapine-based regimen showed greater CR in the acute, delayed, and overall-phases versus the PALO-DEX regimen (OR = 3.97, 95% CrI = 1.02–19.13; OR = 5.62, 95% CrI = 1.66–28.58; OR = 4.79, 95% CrI = 1.40–24.02, respectively). Additionally, it showed greater RNN than the NK-1-RA-based and the PALO-DEX regimens in the delayed phase only (OR = 2.90, 95% CrI = 1.34–5.15; OR = 4.53, 95% CrI = 1.89–10.55, respectively). Olanzapine-, NK-1-RA-, and thalidomide-based regimens did not differ in CR in the three phases. SUCRA probabilities ranked the olanzapine-based regimen as the best option in terms of CR and RNN, while ranking the NK-1-RA-based regimens as the second best option in terms of CR throughout the three phases.

Conclusion

Based on the data included in the analyses, there is insufficient evidence to support adding thalidomide or NK-1-RA to PALO-DEX in preventing CINV induced by HEC. However, adding olanzapine to PALO-DEX achieves better CR and RNN. Olanzapine side-effects and the absence of direct comparisons explain why some guidelines are cautious in suggesting the use of olanzapine.

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Correspondence to Abdullah A. Alhifany.

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Key message

This Bayesian network analysis suggests that there is insufficient evidence to support adding thalidomide or neurokinin-1 receptor antagonists as third agents to palonosetron plus dexamethasone in preventing nausea and vomiting induced by highly emetic chemotherapy. Adding olanzapine as a third agent provides an incremental clinical benefit but side-effects must be considered.

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Alhifany, A.A., McBride, A., Almutairi, A.R. et al. Efficacy of olanzapine, neurokinin-1 receptor antagonists, and thalidomide in combination with palonosetron plus dexamethasone in preventing highly emetogenic chemotherapy-induced nausea and vomiting: a Bayesian network meta-analysis. Support Care Cancer 28, 1031–1039 (2020). https://doi.org/10.1007/s00520-019-05210-4

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Keywords

  • Olanzapine
  • Neurokinin-1 receptor antagonists
  • Thalidomide
  • Palonosetron
  • Dexamethasone
  • Chemotherapy-induced nausea and vomiting
  • Highly emetic chemotherapy