Clinical trialPhase 3

Olanzapine for the Prevention of Chemotherapy-Induced Nausea and Vomiting

N Engl J Med · 2016380 evaluable patients (192 in the olanzapine group and 188 in the placebo group)

Navari RM, Qin R, Ruddy KJ, Liu H, Powell SF, Bajaj M, et al. N Engl J Med. 2016. 375:134-142

Study type: Clinical trial
Phase: Phase 3
Design: Randomised, double-blind, placebo-controlled trial
Sample size: 380 evaluable patients (192 in the olanzapine group and 188 in the placebo group)
Source: N Engl J Med · 2016
Trial registration: NCT02116530

In plain words

Some chemotherapy drugs cause severe nausea and vomiting. In this study, adding the drug olanzapine (10 mg a day for 4 days) to the usual anti-sickness medicines meant patients had less nausea and less vomiting. The main side effect of this medicine was drowsiness, which was most noticeable on the second day and was severe in 5% of patients.

Key results

74% vs 45% (olanzapine vs placebo)

No nausea in the first 24 hours after chemotherapy

P=0.002

42% vs 25%

No nausea from 25 to 120 hours after chemotherapy

P=0.002

37% vs 22%

No nausea over the whole 120-hour period

P=0.002

86% vs 65%

Complete response in the first 24 hours

P<0.001

67% vs 52%

Complete response from 25 to 120 hours

P=0.007

64% vs 41%

Complete response over the whole 120-hour period

P<0.001

Treatment arms and regimens

1Olanzapine group

Olanzapine 10 mg orally daily on days 1 to 4, with dexamethasone, aprepitant or fosaprepitant, and a 5-hydroxytryptamine type 3 (5-HT3) receptor antagonist. Doses of the concomitant drugs before and after chemotherapy were similar in both groups; their dose details are in the full text of the paper.

2Placebo group

Matching placebo daily on days 1 to 4, with dexamethasone, aprepitant or fosaprepitant, and a 5-HT3 receptor antagonist. Dose details of the concomitant drugs in the full text of the paper.

Source of the regimen details: Abstract of the paper

Doses are given for the information of specialists, as in this study’s protocol, and are not a prescription. Every drug must be prescribed by the treating physician for the individual patient.

Study population

Chemotherapy-naive patients receiving highly emetogenic chemotherapy: cisplatin (at a dose of ≥ 70 mg/m² of body surface area) or cyclophosphamide–doxorubicin.

Endpoints

Primary endpoint: prevention of nausea. Secondary endpoint: complete response (no emesis and no use of rescue medication).

Safety and side effects

No grade 5 toxicity was observed. Some patients receiving olanzapine had increased sedation on day 2, which was severe in 5%.

Clinical significance and place in guidelines

This trial shows that adding olanzapine to the standard three-drug regimen (dexamethasone, an NK1 antagonist and a 5-HT3 antagonist) improves nausea prevention and complete response with highly emetogenic chemotherapy. Sedation should be considered in decision-making. The status of this approach in current guidelines (such as ASCO, NCCN and MASCC/ESMO) should be checked separately, as the abstract gives no information on it.

Limitations

Based on the abstract, information on patients' cancer types, long-term follow-up and other limitations is not provided; these should be checked in the full text of the paper. Outcomes were assessed only up to 120 hours after chemotherapy.

Original article (DOI)PubMed ClinicalTrials.gov

This summary was prepared by the editorial team from the published paper; the original paper is the final reference. Read the original abstract on PubMed.