CHICAGO – Olanzapine plus aprepitant, palonosetron, and dexamethasone (APD) can be considered a new standard antiemetic therapy for patients receiving cisplatin-based chemotherapy, according to a speaker at the annual meeting of the American Society for Clinical Oncology.
A 5 mg dose of olanzapine plus APD produced significantly higher complete response (CR) rates than APD plus placebo in a phase 3 trial, said Hironobu Hashimoto, BPharm, of the National Cancer Center Hospital in Tokyo.
In addition, olanzapine plus APD had a significantly longer time to treatment failure and produced higher rates of complete control and total control. However, rates of somnolence, dizziness, and dry mouth were significantly higher with olanzapine plus APD.
In the phase 3study, Mr. Hashimoto and his colleagues evaluated olanzapine at 5 mg plus standard antiemetic therapy (APD) for the prevention of chemotherapy-induced nausea and vomiting.
The trial enrolled 710 patients, ages 22-75 years, who had malignant solid tumors and were receiving cisplatin-based chemotherapy for the first time. The patients were randomized to olanzapine plus APD or APD plus placebo.
There were 354 patients evaluable for efficacy in the olanzapine arm and 351 in the placebo arm. The primary endpoint was CR, which was defined as no vomiting and no rescue medications, in the delayed phase (24 hours to 120 hours).
The CR rate in the delayed phase was 79% in the olanzapine arm and 66% in the placebo arm (P less than .001). The CR rate in the acute phase (0 to 24 hours) was 95% and 89%, respectively (P equal to .002), and the overall CR rate was 78% and 64%, respectively (P less than .001).
The time to treatment failure was significantly longer in the olanzapine arm (P less than .001).
The rate of complete control in the overall period (0 to 120 hours) was 76% in the olanzapine arm and 61% in the placebo arm (P less than .001). Complete control was defined as no emesis, no rescue medication, and no nausea or low-grade nausea.
The rate of total control in the overall period was 59% in the olanzapine arm and 48% in the placebo arm (P = .005). Total control was defined as no emesis, no rescue medication, and no nausea.
Treatment-related adverse events (in the olanzapine and placebo arms, respectively) included constipation (15% and 11%), hiccups (10% and 6%), somnolence (43% and 33%), insomnia (5% and 7%), dizziness (8% and 3%), and dry mouth (21% and 9%).
Adverse events that occurred significantly more often with olanzapine were somnolence (P = .011), dizziness (P = .004), and dry mouth (P less than .001).
This study was sponsored by the Japan Agency for Medical Research and Development (AMED). Mr. Hashimoto said he had nothing to disclose. Other investigators involved in this study disclosed relationships with numerous pharmaceutical companies.
SOURCE: Hashimoto H et al. ASCO 2019. .