Olanzapine a favourable alternative to dexamethasone for CINV

Olanzapine administered at a dose of 5 mg was noninferior to dexamethasone and is associated with fewer adverse effects than dexamethasone for chemotherapy-induced nausea and vomiting (CINV), according to data presented at ESMO 2021.

“CINV is associated with significant deterioration in quality of life. The standard antiemetic therapy for highly emetogenic chemotherapy are combination therapies, and dexamethasone is a necessary component,” said the researchers.

“[D]examethasone offers an advantage over placebo for protection against chemotherapy-induced emesis in both acute and delayed phases … However, dexamethasone has diverse side effects, including moderate-to-severe insomnia, hyperglycaemia, and dyspepsia, which are gathering increasing concerns,” they continued.

“[Moreover,] dexamethasone is not applicable to all cancer patients,” they said. For instance, diabetes, which can occur in more than half of cancer patients, may confound the use of dexamethasone. “[Hence,] dexamethasone might not be a proper antiemesis choice for them … [This also implies that dexamethasone may generally] not be an appropriate antiemetic for use in immunotherapy,” said the researchers.

However, most guidelines recommend dexamethasone-based antiemetic regimens, they pointed out. “[As such,] alternative antiemetic regimens are required,” they said.

Guidelines recommend olanzapine 10 mg for CINV prevention, but the issue of excessive sedation is a concern. Evidence shows that a lower dose (5 mg) may effectively manage CINV and had less serious sedative effects.

To ascertain the feasibility of a dexamethasone-free regimen, researchers evaluated 548 chemotherapy-naïve participants receiving a highly emetogenic cisplatin-based regimen. Participants were randomized 1:1 to receive either olanzapine or dexamethasone on top of a 5-HT₃ RA* (eg, granisetron, ondansetron, or palonosetron) and NK₁ RA** (eg, fosaprepitant or aprepitant). Olanzapine 5 mg was given orally (days 1–4), while dexamethasone was given orally or intravenously within 30 minutes prior to cisplatin administration (12 mg on day 1; 8 mg on days 2–4). [ESMO 2021, abstract LBA64]

Compared with those who received dexamethasone, patients who received olanzapine achieved similar 0–120-hour complete response (CR) rate (83.6 percent vs 84.9 percent; difference, 1.2 percent; p_{noninferiority}=0.003), 25–120-hour CR rate (85.5 percent vs 85.6 percent; difference, 0.1 percent; p_{noninferiority}=0.024), and 0–120-hour no-nausea rate (38.7 percent vs 39.9 percent; difference, 1.2 percent; p_{noninferiority}=0.001).

Adverse effects were more common among individuals receiving dexamethasone compared with those receiving olanzapine (p=0.045, p<0.001, and p<0.001 for constipation, hiccups, and insomnia, respectively).

Taken together, these findings suggest that olanzapine 5 mg may be a noninferior option to dexamethasone in a triplet antiemetic therapy, said the researchers.