Oncologist. 2021 Jun 7. doi: 10.1002/onco.13851. Online ahead of print.
ABSTRACT
BACKGROUND: To reduce the overall exposure to dexamethasone (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-dose combination of netupitant and palonosetron, compared with the guideline-consistent use of 4-day DEX.
PATIENTS AND METHODS: In this open-label, multicenter study, chemo-naïve patients undergoing high-dose cisplatin (≥70 mg/m2 ), were given NEPA and DEX (12 mg) on day 1 and randomized (1:1:1 ratio) to receive either 1) no further DEX (DEX1), 2) oral DEX (4 mg daily) on days 2-3 (DEX3), or 3) DEX (4 mg twice daily) on days 2-4 (DEX4). The primary efficacy endpoint was complete response (CR: no emesis and no rescue medication) during the 5-day overall phase. The non-inferiority margin was set at -15% difference (DEX1 or DEX3 minus DEX4). Secondary efficacy endpoints included complete protection (CP: CR and none or mild nausea).
RESULTS: Two-hundred twenty-eight patients, 76 in each arm, were assessable. Non-inferiority was met for both DEX-sparing regimens and the reference arm, with overall phase CR rates of 76.3% in each of the DEX1 and DEX3 arms and 75.0% in the DEX4 arm (95% CI, -12.3% to 15% for each comparison). During the overall phase, CP rates were similar between groups.
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.
IMPLICATIONS FOR PRACTICE: Dexamethasone (DEX) has traditionally played an integral role in the management of chemotherapy-induced nausea and vomiting (CINV). While generally considered safe, even short-term DEX use is associated with various side effects, and some evidence suggests that steroids may reduce the efficacy of immunotherapies and cellular therapies, if used concurrently. Our study demonstrates, for the first time, comparable antiemetic control during the 5-days post-chemotherapy with a simplified three-drug regimen of NEPA (netupitant/palonosetron) plus single-dose DEX versus the standard 4-day DEX reference treatment in patients undergoing high-dose cisplatin. This represents a clinically relevant achievement as it not only simplifies antiemetic prophylaxis but also offers an opportunity to minimize DEX-related side effects and appropriately use in patients where caution with corticosteroid use is advised.
PMID:34101934 | DOI:10.1002/onco.13851
