Chemo-induced nausea, vomiting? There’s a dexamethasone-free regimen for that

A dexamethasone-free regimen helps improve control of nausea and vomiting in patients receiving “highly emetogenic” chemotherapy, with the antiemetic effect being superior to that of a dexamethasone-based regimen, according to the results of a phase III trial presented at ASCO Breakthrough 2023.

Among 346 adult patients with cancer who were receiving single-day highly emetogenic chemotherapy, those who were assigned to an antiemetic regimen consisting of olanzapine, palonosetron, and fosaprepitant (DEX-free; n=172) had better control of vomiting than those who were assigned to a regimen comprising olanzapine, palonosetron, and dexamethasone (DEX-based; n=174). [ASCO Breakthrough 2023, abstract 133]

Complete response (CR) rates for vomiting, the primary study endpoint, were 79.6 percent in the DEX-free arm and 48.8 percent in the DEX-based arm for the overall period (ie, from chemotherapy initiation to 120 hours), demonstrating the superiority of the dexamethasone-free regimen (p<0.001), reported lead study author Dr Venkatraman Radhakrishnan of Adyar Cancer Institute in Chennai, India.

The difference in CR rates for vomiting was also significant in the acute period (first 24 hours; 94.7 percent vs 85.6 percent; p=0.004) and delayed period (ie, 24 hours to 120 hours; 81.9 percent vs 50.5 percent; p<0.001), Radhakrishnan added.

Likewise, results for nausea were more favourable in the DEX-free than in the DEX-based arm but only for the delayed (CR rates: 53.4 percent vs 39.6 percent; p=0.009) and overall (CR rates: 50.5 percent vs 39.1 percent; p=0.031) periods, he noted. “Actually, in the acute period for nausea, there wasn’t much difference [between the treatment arms].”

For both nausea and vomiting, total control was significantly better in the DEX-free arm than in the DEX-based arm (CR rates: 45.3 percent vs 29.8 percent; p=0.009). The antiemetic effect of the DEX-free regimen was consistently seen in subgroups defined by gender, the type of chemotherapy, the age, radiation, smoking, alcohol, or [whether] the indication was chemo or neoadjuvant, adjuvant, or concurrent.

Looking at toxicities, the treatment arms were similar. However, patients in the DEX-free arm reported experiencing more fatigue (p=0.009) and drowsiness (p=0.002) in the first 24 hours after chemotherapy, whereas those in the DEX-based arm said that they had difficulty sleeping (p<0.001) for days after treatment.

“The quality of lives [according to global health scores] were comparable. But, obviously, patients who got dexamethasone had more nausea and vomiting and insomnia,” Radhakrishnan said.

In either treatment arm, olanzapine was administered at 5 mg once a day on days 1‒4 and palonosetron at 0.25 mg on day 1. Patients in the DEX-free arm also received fosaprepitant at 150 mg on day 1, whereas those in the DEX-based arm received dexamethasone 12 mg instead. The most common chemotherapy used was doxorubicin/cyclophosphamide (66 percent), followed by cisplatin (27 percent).

Clinical breakthrough

Steroids have been the backbone of all antiemetic regimens, with guidelines from major medical oncology societies recommending prophylactic regimens for highly emetogenic chemotherapy that consist of steroids, according to Radhakrishnan.

“Over the course of, say, six to eight cycles of chemotherapy, patients might end up getting probably 200 to 300 milligrams of dexamethasone, which might turn prediabetics to diabetics. [Some] might have hypertension… [A dexamethasone-based regimen] might have so many serious side effects,” he pointed out.

Radhakrishnan believes that the findings from the current study are a clinical breakthrough. “We planned a noninferiority study and ended up showing superiority… It’s taken 4 decades for us to say that dexamethasone is no longer needed as an antiemetic. And I think this is the breakthrough.”