Optimizing antiemetic support in anthracycline-based chemotherapy for early breast cancer: A protocol for a prospective observational study of four-drug antiemetic therapy including fosnetupitant and olanzapine (Preprint)

BACKGROUND Prophylaxis for chemotherapy-induced nausea and vomiting (CINV) in patients receiving highly emetogenic chemotherapy (HEC) is essential. Four-drug antiemetic therapy, consisting of a neurokinin-1 receptor antagonist (NK1RA), a 5-hydroxytryptamine type 3 receptor antagonist (5-HT3RA), dexamethasone (DEX), and olanzapine (OLZ), is currently recommended for HEC. However, the efficacy, optimal dosing schedule, and appropriate dosage of OLZ remain unclear when combined with a highly selective NK1RA, fosnetupitant (FosNTP). OBJECTIVE To evaluate the efficacy and safety of a four-drug antiemetic regimen including FosNTP and OLZ for prophylaxis of CINV in patients receiving anthracycline-based (neo)adjuvant chemotherapy for early breast cancer (EBC) and to explore outcomes with OLZ dose adjustments in the second course. METHODS This single-institution, prospective observational study will receive 100 patients with EBC who undergoes HEC. All patients will receive a four-drug antiemetic regimen consisting of FosNTP, 5-HT3RA, DEX, and the guideline-recommended dose of OLZ administered orally from days –1 to 4. During the second course of treatment, OLZ dosing may be adjusted based on tolerability and patient preference. The primary endpoint is the proportion of patients who experienced no nausea during the overall phase (0–120 h) of the first course, as assessed using the daily visual analog scale. A sample size of 86 was calculated to assess the efficacy of the four-drug antiemetic regimen, including OLZ, assuming an expected no nausea rate of 42%, a threshold no nausea rate of 27% based on historical data, 90% power, and a 1-sided significance level of 5.0%. A single-sample z-test with a normal approximation will be used for the analyses. RESULTS This study was approved by the Ethics Committee in March 2024, and participant recruitment and data collection commenced in May 2024. As of September 2025, approximately 70 participants have been recruited. Data collection is expected to continue until April 2026, and both data collection and analyses are anticipated to be completed in 2027. CONCLUSIONS This study will provide real-world evidence on the effectiveness and safety of a four-drug antiemetic regimen, including FosNTP and OLZ, in patients receiving anthracycline-based HEC and may inform optimal OLZ dosing strategies. CLINICALTRIAL UMIN-CTR UMIN000054250; https://www.umin.ac.jp/ctr/