LBA63 - 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

Background

Olanzapine (OLZ) 5 mg combined with dexamethasone (DEX), neurokinin-1 receptor antagonist (NK₁-RA), and palonosetron (PALO) has been established as the standard for patients (pts) receiving cisplatin (CDDP)-containing highly emetogenic chemotherapy (HEC). This study aimed to clarify the non-inferiority of DEX sparing when combined with NK₁-RA, PALO, and OLZ in CDDP-containing HEC.

Methods

Pts with a solid malignant tumor who were treated with CDDP (≥50 mg/m²) for the first time were randomly assigned to Arm D4 (DEX on days 1-4) or Arm D1 (DEX on day 1). The primary endpoint was complete response (CR), which was defined as no emetic episodes and no rescue antiemetic medication, during the delayed phase (24-120 h after the start of CDDP). Secondary endpoints included CR rates in the acute (0-24 h) and overall (0-120 h) phases, complete control (CC) and total control (TC) rates, adverse events with the patient-reported outcome (PRO) CTCAE, and QOL with EORTC QLQ-C30 on day 8. We assumed delayed CR rates would be 75 % in both arms. The planned sample size of 280 provided a power of 80% to detect the non-inferiority of Arm D1 to D4 with the margin of difference by 15% in delayed CR rate (one-sided α = 0.025).

Results

Between October 2018 and March 2021, 281 pts were enrolled, out of which 274 pts were evaluable. Baseline characteristics were well-balanced. CR, CC, and TC are shown in the table. In PRO-CTCAE evaluation, pts with nausea (P < 0.01), appetite loss (P < 0.01), and diarrhea (P = 0.015) were more observed in Arm D1; however, there was no significant difference in the severity of nausea. Scores in global health status in QOL were not significantly different between the two arms (P = 0.38). Table: LBA63

Conclusions

DEX administration on days 2 to 4 can be spared when combined with NK₁-RA, PALO, and OLZ 5 mg in CDDP-containing HEC.

Clinical trial identification

UMIN000032269.

Editorial acknowledgement

We thank the support for the writing of the abstract from Dr. Takashi Kawaguchi.

Legal entity responsible for the study

The authors.

Funding

Japan Agency for Medical Research and Development.

Disclosure

H. Arioka: Financial Interests, Personal, Speaker’s Bureau: Ono Pharmaceutical Co., LTD; Financial Interests, Personal, Speaker’s Bureau: Pfizer; Financial Interests, Personal, Speaker’s Bureau: Chugai Pharmaceutical; Financial Interests, Personal, Advisory Board: Taiho Pharmaceutical; Financial Interests, Personal, Advisory Board: Otsuka Pharmaceutical; Financial Interests, Personal, Advisory Board: Delta-Fly Pharma. N. Izawa: Financial Interests, Personal, Speaker’s Bureau: Lilly; Financial Interests, Personal, Speaker’s Bureau: Bristol Myers Scib; Financial Interests, Personal, Speaker’s Bureau: Taiho; Financial Interests, Personal, Speaker’s Bureau: Daiichi Sankyo; Financial Interests, Personal, Speaker’s Bureau: Takeda pharm; Financial Interests, Personal, Speaker’s Bureau: Guardant health. T. Yamaguchi: Financial Interests, Personal and Institutional, Other, Member of Endowment Department: Ono Pharmaceutical Co., Ltd.; Financial Interests, Personal, Writing Engagements: Ono Pharmaceutical Co., Ltd. T.E. Nakajima: Financial Interests, Personal, Invited Speaker: Takeda pharm; Financial Interests, Personal, Invited Speaker: Taiho; Financial Interests, Personal, Invited Speaker: Bristol Myers Scib; Financial Interests, Personal, Invited Speaker: Sanofi; Financial Interests, Personal, Invited Speaker: Chugai; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Invited Speaker: Ono Pharm; Financial Interests, Personal, Invited Speaker: Boehringer Ingelheim Japan; Financial Interests, Personal, Invited Speaker: Dainipponsumitomo; Financial Interests, Personal, Invited Speaker: Amgen; Financial Interests, Personal, Research Grant: Chugai; Financial Interests, Personal, Research Grant: Nihon kayaku. All other authors have declared no conflicts of interest.