295TiP - Assessing the benefit of NEPA (fixed combination of netupitant/palonosetron) for preventing chemotherapy-induced nausea and vomiting (CINV) in patients at increased emetic risk receiving moderately emetogenic chemotherapy

Background

In patients receiving moderately emetogenic chemotherapy (MEC), antiemetic guidelines lack evidence to recommend an NK₁ receptor antagonist (RA) for all patients; therefore, they endorse a 5-HT₃ RA + dexamethasone (DEX). However, the NCCN guidelines recognize that this approach is inadequate prophylaxis for many patients and include an NK₁ RA-containing option selectively for those with individual emetic risk factors (e.g., prior CINV, age <50, female). Evidence shows that NEPA (a fixed combination of an NK₁ RA, (fos)netupitant, and a 5-HT₃ RA, palonosetron) is effective in a non-interventional real-world setting (Zelek 2021) in a heterogeneous population of patients with cancer receiving highly emetogenic or MEC and in patients with CINV risk factors.

Trial design

This is a phase IV, randomized, open-label, multicenter, multinational study conducted in 7 countries (NCT04817189). An algorithm incorporating 7 predictive risk factors (adapted from Dranitsaris, Ann Oncol 2017) is used to select patients at increased risk of CINV. Suitable patients ≥18 years, naïve or non-naive to chemotherapy, with a diagnosis of any cancer scheduled to receive 3 consecutive cycles of an intravenous MEC regimen, are randomized to either NEPA + DEX or the 5-HT₃ RA + DEX standard of care. A single dose of oral NEPA + 8 mg DEX (or equivalent corticosteroid) or a 5-HT₃ RA + DEX is administered ∼1 hour before MEC on day 1. In patients receiving certain MEC with known potential for delayed CINV, the use of DEX on days 2 and 3 can be considered. The Multinational Association of Supportive Care in Cancer (MASCC) Antiemesis Tool (MAT) is used to capture nausea and vomiting post-chemotherapy. The primary endpoint is complete response (CR: no emesis, no rescue use) during the overall (0-120 h) phase post-chemotherapy over 3 cycles. A generalized linear model will analyze CR over 3 cycles of MEC with logit link function, binomial distribution, and with study treatment, carboplatin use, and the country as factors. A total of 530 patients are planned (265/group). Enrollment is open; as of July 7, 141 patients have been randomized.

Clinical trial identification

NCT04817189.

Legal entity responsible for the study

Helsinn Healthcare.

Funding

Helsinn Healthcare.

Disclosure

A. Molasiotis: Financial Interests, Personal, Invited Speaker, Lead investigator in a trial supported by Helsinn. I receive a small compensation for this role: Helsinn. M.S. Aapro: Financial Interests, Personal, Invited Speaker: Amgen, ViforPharma, Fresenius Kabi, European Cancer Organisation, SIOG; Financial Interests, Institutional, Other, Grant to SPCC: BMS, ExactSciences, Pfizer, Novartis; Financial Interests, Institutional, Invited Speaker, Grant to SPCC: Helsinn; Financial Interests, Institutional, Other, GRANT TO SPCC: Mundipharma; Financial Interests, Personal, Advisory Board: Astellas; Financial Interests, Institutional, Invited Speaker: SPCC; Non-Financial Interests, Personal, Advisory Role, Confidentiality agreement: Various companies; Non-Financial Interests, Personal, Leadership Role: European Cancer Organisation, SPCC, SIOG; Non-Financial Interests, Personal, Member: MASCC, SBOC, ASCO; Other, Personal, Other, SAB member: European School of Oncology. A. Alonzi: Financial Interests, Personal, Full or part-time Employment: Helsinn Healthcare SA. K. Jordan: Financial Interests, Personal, Advisory Board, Adverse Board / Bisphoshonates: Amgen; Financial Interests, Personal, Advisory Board, G-CSF: Hexal/Sandoz; Financial Interests, Personal, Invited Speaker, NEPA: Helsinn; Financial Interests, Personal, Advisory Board, E-Health Application: Volontis; Financial Interests, Personal, Invited Speaker, ASCO direct: Art Tempi; Financial Interests, Personal, Invited Speaker, Adverse Event Management: Amgen; Financial Interests, Personal, Invited Speaker, ASCO Summary: Hexal, Onkowissen; Financial Interests, Personal, Invited Speaker, Adverse Events Management: MSD, Roche; Financial Interests, Personal, Advisory Board, New drug: AstraZeneca; Financial Interests, Personal, Invited Speaker, Supportive Care: Mundipharma; Financial Interests, Personal, Invited Speaker, Antiemetic Update: Riemser; Financial Interests, Personal, Invited Speaker, ESMO Today: Art tempi; Financial Interests, Personal, Invited Speaker, OnkoUpdate: med update GmbH; Financial Interests, Personal, Invited Speaker, Update on Antiemetics: Vifor; Financial Interests, Personal, Invited Speaker, Immunoglobulins: Shire (Takeda); Financial Interests, Personal, Advisory Board, Side effect management: Karyopharma; Financial Interests, Personal, Advisory Board, side effect managment: BD Solution; Financial Interests, Personal, Royalties, Coauthor: Kluwer (UpToDate); Financial Interests, Personal, Royalties, Associate Editor of Annals of Oncology: Elsevier; Financial Interests, Institutional, Invited Speaker, Antiemetic Phase III study, Starts in May 2021: Helsinn; Non-Financial Interests, Personal, Member: ASCO, MASCC, DGHO; Non-Financial Interests, Personal, Leadership Role, Associate Chair of the Supportive Care Group of the German Cancer Society: AGSMO; Non-Financial Interests, Personal, Leadership Role, Associate Chair of the Supportive Care Group: AIO; Non-Financial Interests, Personal, Leadership Role, Educational Committee Chair, SE Supportive Care Guideline group: ESMO; Non-Financial Interests, Personal, Advisory Role, Advisory and expert activities: Deutsche Krebshilfe, German Cancer aid, Leopoldina, Federal Ministry of Education and Research (BMBF), Hamburger Cancer Society. E.J. Roeland: Financial Interests, Personal, Advisory Role: Aim Specialty Health, Asahi Kasei, Astellas Pharma, BASF, Helsinn Therapeutics, HERON, Napo Pharmaceuticals, Oragenics, Pfizer/EMD Serono, Vector Oncology; Financial Interests, Personal, Expert Testimony: Regents of University of California . L.S. Schwartzberg: Financial Interests, Personal, Full or part-time Employment: OneOncology; Financial Interests, Personal, Stocks/Shares: OneOncology; Financial Interests, Personal, Leadership Role: OneOncology; Financial Interests, Personal, Invited Speaker: Seagen, Merck, Pfizer. C. Terrasanta: Financial Interests, Personal, Full or part-time Employment: Helsinn Healthcare SA. S. Olivari: Financial Interests, Personal, Full or part-time Employment: Helsinn Healthcare SA. All other authors have declared no conflicts of interest.