1815MO - Two simplified dexamethasone (DEX)-sparing regimens with NEPA for the prevention of emesis caused by cisplatin (DDP): A phase III, controlled, non-inferiority trial

Background

To reduce the overall exposure to DEX in 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 NEPA, a fixed combination of the NK-1 receptor antagonist (RA), netupitant and the pharmacologically distinct 5-HT₃RA, palonosetron, compared with the guideline-recommended 4-day use of DEX.

Methods

In this open-label, multicenter study, chemo-naïve lung cancer patients receiving cisplatin (>=70 mg/m²), were given a single oral dose of NEPA and DEX (12 mg i.v.) prior to chemotherapy and randomized (1:1:1) to receive no further DEX (DEX1), oral DEX (4 mg once daily) on days 2 and 3 (DEX3), or oral DEX (4 mg twice daily) on days 2 to 4 (DEX4; reference arm). The primary efficacy endpoint was complete response (CR: no emesis and no use of rescue medication) during the overall (days 1-5) phase. Non-inferiority was defined as a lower 95% CI greater than the non-inferiority margin threshold of -15% difference (Arms DEX1 or DEX3 minus Arm DEX4). Impact of Chemotherapy-Induced Nausea and Vomiting (CINV) on daily life as assessed by the Functional Living Index-Emesis (FLIE) questionnaire was also evaluated.

Results

A total of 222 patients (76% male), 74 in each arm, were evaluated. CR rates during the overall and delayed phases were 77.0% in Arms DEX1 and DEX3 and 74.3% in Arm DEX4 (95% CI, -11.1% to 16.5%). No significant differences were observed between groups in proportions of patients who reported no impact on daily life due to nausea, vomiting, or both during the 5-day observation period after cisplatin administration.

Conclusions

Since efficacy results were comparable between the two DEX-sparing regimens in this study, we conclude that the simplified three-drug regimen with NEPA plus single-dose DEX is an option that is not associated with significant reduction in anti-emetic control during the 5-day period or an impact on patient functioning in the setting of cisplatin.

Clinical trial identification

NCT04201769 EudraCT Number: 2015-005704-29 Protocol Number: LUNG-NEPA.

Editorial acknowledgement

Legal entity responsible for the study

Consorzio Oncotech.

Funding

Has not received any funding.

Disclosure

L. Celio: Advisory/Consultancy: Italfarmaco, Kyowa. D. Cortinovis: Advisory/Consultancy: Helsinn Healthcare SA. L. Cavanna: Advisory/Consultancy: AstraZeneca, Merck; Travel/Accommodation/Expenses: Celgene, Pfizer, Ipsen. R. Chiari: Speaker Bureau/Expert testimony, Conventions speaker: Roche, MSD, BMS, Astrazeneca, Pfizer. E. Bonizzoni: Advisory/Consultancy, Spot consultancy assignments by Italfarmaco and statistical consultant at Helsinn: Italfarmaco, Helsinn. S. Pilotto: Honoraria (self), Speaker Bureau/Expert testimony, S.P. received honoraria or speakers’ fee from Astra-Zeneca, BMS, Boehringer Ingelheim, MSD and Roche: Astra-Zeneca, BMS, Boehringer Ingelheim, MSD and Roche. S. De Placido: Advisory/Consultancy: GSK, Novartis, Roche, Celgene, Astrazeneca, Amgen, Eisai, Italfarmaco, Pfizer, Eli Lilly; Speaker Bureau/Expert testimony, Invited speech: GSK, Novartis, Roche, Celgene, Astrazeneca, Amgen, Pfizer, Eli Lilly. E. Bria: Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses, E.B. received speakers’ and travels’ fee: MSD, Astra-Zeneca, Celgene, Pfizer, Helsinn, Eli-Lilly, BMS, Novartis and Roche; Research grant/Funding (institution), E.B. received institutional research grants: Astra-Zeneca, Roche. All other authors have declared no conflicts of interest.