Multicenter phase 3 trial of olanzapine or prochlorperazine added to antiemetic therapy for persistent chemotherapy-induced nausea

A phase 3 trial at 23 NCI Community Oncology Research Program (NCORP) centers evaluated whether adding olanzapine or prochlorperazine to standardized cycle 2 antiemetic prophylaxis reduces persistent nausea compared with placebo in adult women receiving moderately or highly emetogenic therapy for breast cancer. Eligible participants recorded a cycle 1 nausea score of 3 or greater (1-7 scale). Participants were randomized 1:1:1 during cycle 2 to placebo (n=91), prochlorperazine (10 mg every 8 hours, days 1-4; n=110), or olanzapine (10 mg once daily, days 1-4; n=109), added to netupitant/palonosetron plus dexamethasone. The primary outcome was change in average nausea score from cycle 1 to cycle 2. Compared with placebo, average nausea improved with prochlorperazine (between-group difference -0.44; p=0.01) and olanzapine (-0.57; p=0.001). Olanzapine reduced maximum nausea more than prochlorperazine (-0.59; p=0.02) and improved FACT-G quality-of-life scores over placebo (difference 4.91; p=0.006) and prochlorperazine (5.80; p=0.001). Adverse events were primarily grade 1-2, with no toxicity-related discontinuations. The authors conclude that adding olanzapine or prochlorperazine to standard cycle 2 antiemetic prophylaxis reduced persistent chemotherapy-induced nausea compared with placebo. Olanzapine produced greater improvement in maximum nausea and quality of life than prochlorperazine and is an effective escalation option, with prochlorperazine a reasonable alternative when olanzapine is unsuitable.