Higher Rates of Nausea, Appetite Loss Reported With Dexamethasone-Sparing Regimens

Patient-reported outcomes (PROs) from the phase 3 SPARED trial (UMIN000032269) showed that despite consistency in global health status, patients experienced worse nausea and appetite loss with dexamethasone-sparing approaches.¹

In a poster presented at the 2022 Supportive Care in Cancer Annual Meeting, investigators evaluated PROs-common terminology criteria for adverse events (PRO-CTCAE) version 1.0 and via CTCAE version 4 for those who received dexamethasone-sparing regimen (n = 139) vs those who received standard dexamethasone (n = 136).

In the PRO analysis, severe appetite loss occurred in 29.4% of patients in the sparing arm vs 17.3% of patients in the standard-regimen arm (P < .01). In terms of mild appetite loss, the rates were 77.2% vs 59.7%, respectively.

Mild nausea was reported at a higher frequency for patients in the dexamethasone-sparing arm (58.1%) vs the standard arm (40.3%); severe nausea occurred only slightly higher rates (5.9% vs 5.0%) (P < .01). Severe and mild nausea was also higher with the limited regimen with 3.7% of patients reporting severe events and 55.1% reporting mild events compared with 2.2% and 38.8% of patients in the standard arm, respectively.¹

In addition to these events, the frequency of headaches was also significantly higher among patients who received the dexamethasone-sparing regimen: 41.2% of patients reported mild headaches and 2.2% reported severe headaches compared with 21.6 of patients reporting mild and 1.4% reporting severe headaches in the standard-of-care arm (P < .01).

Further in the analysis via CTCAE v4.0, any-grade anorexia was significantly higher in the dexamethasone-sparing arm (78.7%) vs the standard-of-care arm (55.4%). However, grade 3 or higher anorexia was higher among patients in the standard arm (4.3%) vs the sparing regimen arm (2.9%).

No vomiting rates as assessed by numeric rating scales (NRS) were not significant across treatment arms in the delayed, acute (0 to 24 hours post cisplatin) and overall (0 to 120 hours post cisplatin) phases.

Severity of the nausea of NRS greater than 1 in the delayed cohort for patients who received the dexamethasone-sparing regimen was 47.8% vs 35.5% in the standard-of-care arm (P = .04). In the overall cohort a similar trend was observed with 50.0% of patients reporting nausea in the experimental arm vs 37.7% in the standard arm (P = .04). There was no significant difference in nausea severity across phases when assessed by NRS greater than 3.

Although short-term dexamethasone administration contributes to the reduction of chemotherapy-induced nausea and vomiting (CIVN), the therapy has its own toxicity profile that should be taken into consideration. Investigators sought to determine the risk benefit ratio of reducing the administration of dexamethasone in patients receiving cisplatin-based chemotherapy.

Patients with solid tumors were enrolled to the SPARED trial received standard of care olanzapine 5 mg combined with dexamethasone, neurokinin-1 receptor antagonist, and palonosetron receiving cisplatin-based chemotherapy of at least 50 mg/m². They were randomly assigned to receive a dexamethasone-sparing regimen (ie, only day 1) or standard of care regimen with dexamethasone administered on days 1 to 4.^1,2

The baseline characteristics were well-balanced between the patient arms with most patients having an ECOG performance status of o (76.3% vs 77.0%) and median age of 64 years (range, 25-74). Primary tumors were reported as esophageal (38.1% vs 40.3%, respectively), head and neck (26.6% vs 23.0%), lung (20.1% vs 18.0%), gastric (4.3% vs 7.2%), or other (10.8% vs 11.5%). Most patients received cisplatin-based chemotherapy at 70 mg/m² or higher.

The primary end point was complete response (CR) rate, defined as no emetic episodes and no rescue antiemetic medication during the first 24 to 120 hours (delayed phase) following cisplatin.² In data reported at the ESMO Congress 2021, outcomes with the dexamethasone-sparing regimen were noninferior to those reported in the standard of care arm (P = .023). The CR rate were 75.0% vs 79.4%, respectively, for a risk difference of –4.1 (95% CI, –14.1 to 6.0).

The data reported in the poster were secondary end points of the trial. Patients were administered the PRO-CTCAE and quality of life questionnaire on day 0 for baseline. Nausea/vomiting assessment via numeric rating scale (NRS), PRO-CTCAE and CRCAE were assessed on days 2 through 6, and an additional quality of life assessment was given on day 8 after discharge.¹

The investigators concluded that further studies are needed to determine which patients are best suited for dexamethasone-sparing approaches.

References

1. Iihara H, Makuuchi M, Kawaguchi T, et al. Patient-reported outcomes with dexamethasone sparing in CDDP-based chemotherapy: a randomized, placebo-controlled, phase III study (SPARED trial). Presented at: 2022 Supportive Care in Cancer Annual Meeting. June 22-24, 2022; Toronto; Ontario.
2. Shimomura K, Minatogawa H, Mashiko T, et al. Placebo-controlled, double-blinded phase Ⅲ study comparing dexamethasone on day 1 with dexamethasone on days 1 to 4, with combined neurokinin-1 receptor antagonist, palonosetron, and olanzapine in patients receiving cisplatin-containing highly emetogenic chemotherapy: SPARED trial. Ann Oncol. 2021;32(suppl 5):S133901340. doi:10.1016/j.annonc.2021.08.2144