Noninferiority study evaluating dexamethasone (DEX)-sparing regimens administered with NEPA, a fixed combination of netupitant and palonosetron, for the prevention of chemotherapy-induced nausea and vomiting (CINV) caused by high-dose cisplatin.

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12093 Background: Corticosteroids such as DEX continue to play a key role for the prevention of CINV. Although they are generally considered safe when used in combination with other anti-emetic agents, corticosteroids can cause a range of side effects. To reduce the overall exposure to DEX in patients receiving cisplatin-based chemotherapy, we evaluated the non-inferiority of DEX on day 1, with or without low-dose DEX on days 2 and 3, combined with oral NEPA, a fixed combination of the NK1 receptor antagonist (RA), netupitant and 5-HT3 RA, palonosetron, compared with NEPA plus the guideline-recommended use of 4-day DEX (reference arm). Non-inferiority was met for both DEX-sparing regimens and the reference arm for the primary endpoint of complete response (CR: no emesis and no rescue use) during the overall (0-120h) phase post-chemotherapy. In this analysis secondary efficacy endpoints were evaluated for the single-dose DEX-sparing group versus the 4-day DEX arm. Methods: In this analysis from an open-label, multicenter study (ClinicalTrials.gov NCT04201769) chemotherapy-naïve patients undergoing high-dose cisplatin (≥70 mg/m2) received either NEPA and DEX (12 mg) on day 1 only or NEPA and DEX [12 mg on day 1 plus 4 mg twice daily on days 2-4 (DEX4)]. Efficacy endpoints included complete protection (CR plus no significant nausea), no emesis, and no significant nausea (<25 mm on a 100 mm visual analog scale) during the acute (0-24h), delayed (>24-120h) and overall phases. The non-inferiority margin was set at -15% difference (DEX1 minus DEX4). Results: One-hundred fifty-two patients, 76 in each arm, were included. Non-inferiority was met for the DEX1 arm and the DEX4 reference arm for all efficacy endpoints (Table). Conclusions: A simplified regimen of NEPA plus single-dose DEX offers comparable CINV prevention throughout 5 days post-chemotherapy with the advantage of sparing patients additional doses of DEX in the high emetic risk setting of cisplatin-based chemotherapy. Clinical trial information: NCT04201769. [Table: see text]