P4-13-03: Retrospective Analysis of Palonosetron Compared with Older 5-HT3 Receptor Antagonists (Ondansetron, Dolasetron, and Granisetron) in Preventing Anthracycline-Induced Nausea and Vomiting in Breast Cancer Patients from Four Phase 3 Trials.
Authors: HS Rugo, L Schwartzberg, GR Morrow, SY Barbour, G Ballinari, MD Thorn, D Cox
Journal: Cancer Research (2011)

Abstract In patients with breast cancer, the risk of developing chemotherapy-induced nausea and vomiting (CINV) is particularly high due to the common use of highly emetogenic chemotherapy coupled with pt-related risk factors including female gender and young age. Despite prophylactic antiemetics, controlling CINV is difficult in this high risk population, particularly in the delayed phase following CT. Palonosetron, a potent 5-HT3 receptor antagonist (RA) with a distinctly different pharmacokinetic and receptor binding profile, has demonstrated improved CINV protection compared to older 5-HT3 RAs in phase 3 and 4 clinical trials in a variety of settings and tumor types. We conducted a retrospective subset analysis of pts with breast cancer, the majority of whom (89%) received anthracycline combination chemotherapy (doxorubicin or epirubicin and cyclophosphamide, AC/EC) from four phase 3, randomized, double-blind, parallel group studies to assess the comparative effectiveness and safety of single IV doses of palonosetron (0.25 or 0.75 mg) versus older 5HT3-RAs (ondansetron 32 mg, dolasetron 100 mg, and granisetron 3 mg) in preventing CINV in pts receiving this highly emetogenic chemotherapy. The primary efficacy evaluation was for complete response (CR), defined as the proportion of patients with no emetic episodes &amp; no use of rescue medication during 0–24hrs (acute), &amp;gt;24-120hrs (delayed), &amp; 0–120hrs (overall) using a logistic regression model. A comparative descriptive safety assessment was also performed. A total of 1197 patients with breast cancer were included in this analysis (palonosetron n=714; older 5HT3-RAs n=483). Higher CR rates were seen for palonosetron vs. older 5HT3-RAs during the acute (63.4% vs 59.4%, p= 0.08), delayed (59.2% vs. 44.9%, p&amp;lt;0.0001) and overall (50.7% vs.38.5%, p&amp;lt;0.0001) phases. Rates for CR were similarly higher for palonosetron-treated patients in the large subgroup of patients receiving AC/EC based chemotherapy. Consistent improvements associated with palonosetron were seen for secondary endpoints of complete control (CR + no more than mild nausea), no emesis, and severity of nausea. The adverse event (AE) profile for palonosetron was similar to older 5HT3-RAs, with headache and constipation being the most commonly reported treatment-related AEs with similar incidences for all 5-HT3 RAs. This retrospective analysis of patients with breast cancer, including a large subgroup receiving anthracycline-based highly emetogenic chemotherapy, demonstrated significantly improved CINV prevention with palonosetron compared to older 5HT3-RAs, particularly in the delayed phase. Safety was comparable. This data has important implications for current CINV prevention guidelines. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-13-03.