A nationwide double-blind phase III randomized clinical trial (RCT) of olanzapine vs. prochlorperazine for the treatment of refractory nausea in patients receiving moderately or highly emetogenic chemotherapy among NCI Community Oncology Research Pro

185 Background: Despite advances in antiemetics given during chemotherapy, nausea remains a clinically significant issue and greatly impairs quality of life (QOL). Current ASCO guidelines recommend olanzapine or prochlorperazine for refractory chemotherapy-induced nausea. However, there is a lack of direct empirical comparisons to establish their relative efficacy. Methods: The URCC NCORP Research Base and 21 NCORP practices enrolled 1,363 chemotherapy-naïve patients with breast cancer starting a high/moderate emetogenic chemotherapy regimen to this Phase III RCT (NCT03367572). Antiemetics were prescribed per ASCO guidelines. Screening occurred during Cycle 1, followed by randomization for Cycle 2. Those with ≥ moderate nausea (≥3 on a 1-7 scale) in Cycle 1 and willing to continue were randomized (1:1:1 ratio) into 3 arms (n=310): 1) ASCO regimen plus olanzapine (OLZ), 2) ASCO regimen plus prochlorperazine (PC), or 3) ASCO regimen plus placebo. Nausea was evaluated using a four-day home diary (4x daily), with the primary outcomes being changes in average (avg) and maximum (max) nausea. FACT-G measured QOL. Intent-to-treat primary analyses (ANOVA and Cohen’s Δ effect size) evaluated whether OLZ or PC improved nausea, testing between-arm differences in nausea change from Cycle 1 to 2 compared to placebo at a p=0.025 significance level corrected for 3 arms. Results: The median age was 50.7y, with 80.7% White/12.3% Black/5.8% Asian/4.2% Latino, and evenly distributed across groups. The change in avg nausea score was statistically significant for the OLZ (avg change = −1.07: Cohen’s Δ = 0.49) and PC arms (avg change = −0.94: Cohen’s Δ = 0.38) compared to the placebo (avg change = −0.50; p <0.001 vs OLZ, p = 0.01 vs PC). Similar but larger changes were noted for change in max nausea score in the OLZ (max change = −2.57: Cohen’s Δ = 0.86) and PC arms (max change = −2.01: Cohen’s Δ = 0.47) against the placebo (max change = −1.30; p <0.001 vs OLZ, p <0.01 vs PC). The OLZ arm had a clinically significant change in overall QOL from pre-chemo to Cycle 2 vs placebo (FACT-G mean difference = +4.91; p = 0.006) but the PC arm vs placebo did not (FACT-G mean difference = −0.87; p = 0.61). OLZ exhibited superiority over PC in terms of changes in max nausea (mean difference = −0.56; p = 0.023) and QOL (FACT-G mean difference = +5.80; p = 0.006), but not for avg nausea (mean difference = −0.13; p = 0.418). Conclusions: OLZ and PC, when added to ASCO guidelines, each significantly reduces refractory nausea. OLZ demonstrates superior max nausea control with clinically and statistically significant improvements in QOL. This study fills the gap in empirical comparisons and solidifies OLZ's position as a promising intervention for refractory nausea. Clinical trial information: NCT03367572 .