Abstract P3-09-02: Optimal anti-emetic choice for breast cancer patients receiving anthracycline and cyclophosphamide-based chemotherapy - A systematic review and network meta-analysis of randomized controlled trials
Authors: Ng TL , Clemons M , Kuchuk I , Roscoe J , Hutton B 
Published: August 2014

Background: International expert consensus groups such as ASCO (JCO 2011) and MASCC (Ann of Oncol. 2010) recommend that patients (pts) receiving anthracycline and cyclophosphamide-based chemotherapy (A&C-CT) regimens receive an anti-emetic combination of 5HT3 antagonist (day 1), NK1 receptor antagonist (day/s 1 or 1-3), and dexamethasone (days 1-3/4). Clinical experience would suggest that Total Control (no episodes of chemotherapy-induced nausea and vomiting [CINV] and no rescue anti-emetic use for 5 days after CT) is often not achieved. We therefore sought to use Network meta-analysis (NMA) to provide a quantitative summary of existing randomised controlled trials (RCTs) to identify the optimal anti-emetic regimen for these pts.

Methods: A peer reviewed search of RCTs assessing combination anti-emetic regimens in breast cancer pts on A&C-CT was performed using Medline, Embase and Cochrane CENTRAL. No additional restriction criteria were employed. Two individuals independently screened citations and full text articles to identify eligible RCTs. Pt and study characteristics, as well as, outcome data were collected to ensure studies were sufficiently similar to include in the NMA. The primary outcome was Total Control of CINV (no nausea, no vomiting, and no rescue anti-emetics for 5 days). Secondary outcomes included Complete Response (no vomiting and no rescue medications for 5 days), No Vomiting and No Nausea in the acute (0-24 hrs) and delayed (24-120 hrs) periods, respectively.

Results: From 962 citations identified, 152 were retained after abstract screening, and 20 retained after full-text screening. Trials were published from 1990 to 2012. There was limited reporting of pt characteristics and CINV outcomes beyond the first CT cycle. The majority of comparisons in the network of treatments were supported by only one RCT. The significant heterogeneity in anti-emetic regimens (n = 21) mandated combining treatment doses and durations to make NMA feasible. Six out of 20 studies reported Total Control, occurring in a mean proportion of 26.9% (23 - 65%) of pts. Complete Response was reported in 11/18 trials, occurring in a mean of 49.8% (31.2% - 79.3%) of pts.

Conclusions: Clinical experience suggests that despite best practice recommendations, many pts do not achieve Total Control of CINV. In preparing for a NMA, we identified marked heterogeneity between trials. This included variability in study design, sample size, treatment agents, duration of agents used, and in reporting of pt characteristics and outcome measures. Given these limitations, despite the recommendations of consensus groups, we have yet been able to make any firm decision on the optimal anti-emetic regimen based on the evidence at this time. We will present findings from our NMA, which will try to account for these limitations. However, if anti-emetic care is to be improved future pragmatic RCTs that include both nausea and vomiting outcomes are clearly required.

Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P3-09-02.