Standard Versus Modified Ipilimumab, in Combination With Nivolumab, in Advanced Renal Cell Carcinoma: A Randomized Phase II Trial (PRISM).

Autor:	Vasudev NS; Leeds Institute of Medical Research at St James's, University of Leeds, St James's University Hospital, Leeds, United Kingdom., Ainsworth G; Clinical Trials Research Unit, University of Leeds, Leeds, United Kingdom., Brown S; Clinical Trials Research Unit, University of Leeds, Leeds, United Kingdom., Pickering L; Royal Marsden Hospital, London, United Kingdom., Waddell T; Department of Medical Oncology, Christie Hospital, Manchester, United Kingdom., Fife K; Addenbrooke's Hospital, Cambridge, United Kingdom., Griffiths R; The Clatterbridge Cancer Centre, Liverpool, United Kingdom., Sharma A; Mount Vernon Cancer Centre, Middlesex, United Kingdom., Katona E; Clinical Trials Research Unit, University of Leeds, Leeds, United Kingdom., Howard H; Clinical Trials Research Unit, University of Leeds, Leeds, United Kingdom., Velikova G; Leeds Institute of Medical Research at St James's, University of Leeds, St James's University Hospital, Leeds, United Kingdom., Maraveyas A; Castle Hill Hospital, Hull, United Kingdom., Brown J; Department of Oncology and Metabolism, University of Sheffield, Sheffield, United Kingdom., Pezaro C; Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, United Kingdom., Tuthill M; Department of Oncology, Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom., Boleti E; Royal Free London NHS Foundation Trust, London, United Kingdom., Bahl A; Bristol Haematology and Oncology Centre, University Hospitals Bristol and Weston NHS Foundation Trust, Bristol, United Kingdom., Szabados B; Barts Cancer Institute, Queen Mary University of London, London, United Kingdom., Banks RE; Leeds Institute of Medical Research at St James's, University of Leeds, St James's University Hospital, Leeds, United Kingdom., Brown J; Leeds Institute of Medical Research at St James's, University of Leeds, St James's University Hospital, Leeds, United Kingdom., Venugopal B; Institute of Cancer Sciences, University of Glasgow, Beatson West of Scotland Cancer Centre, Glasgow, United Kingdom., Patel P; Division of Cancer & Stem Cells, School of Medicine, University of Nottingham, Nottingham, United Kingdom., Jain A; The Royal Wolverhampton NHS Trust, Wolverhampton, United Kingdom., Symeonides SN; Edinburgh Cancer Centre, Western General Hospital, NHS Lothian, Edinburgh, United Kingdom., Nathan P; Mount Vernon Cancer Centre, Middlesex, United Kingdom., Collinson FJ; Clinical Trials Research Unit, University of Leeds, Leeds, United Kingdom., Powles T; Barts Cancer Institute, Queen Mary University of London, London, United Kingdom.
Jazyk:	angličtina
Zdroj:	Journal of clinical oncology : official journal of the American Society of Clinical Oncology [J Clin Oncol] 2024 Jan 20; Vol. 42 (3), pp. 312-323. Date of Electronic Publication: 2023 Nov 06.
DOI:	10.1200/JCO.23.00236
Abstrakt:	Purpose: Ipilimumab (IPI), in combination with nivolumab (NIVO), is an approved frontline treatment option for patients with intermediate- or poor-risk advanced renal cell carcinoma (aRCC). We conducted a randomized phase II trial to evaluate whether administering IPI once every 12 weeks (modified), instead of once every 3 weeks (standard), in combination with NIVO, is associated with a favorable toxicity profile. Methods: Treatment-naïve patients with clear-cell aRCC were randomly assigned 2:1 to receive four doses of modified or standard IPI, 1 mg/kg, in combination with NIVO (3 mg/kg). The primary end point was the proportion of patients with a grade 3-5 treatment-related adverse event (trAE) among those who received at least one dose of therapy. The key secondary end point was 12-month progression-free survival (PFS) in the modified arm compared with historical sunitinib control. The study was not designed to formally compare arms for efficacy. Results: Between March 2018 and January 2020, 192 patients (69.8% intermediate/poor-risk) were randomly assigned and received at least one dose of study drug. The incidence of grade 3-5 trAEs was significantly lower among participants receiving modified versus standard IPI (32.8% v 53.1%; odds ratio, 0.43 [90% CI, 0.25 to 0.72]; P = .0075). The 12-month PFS (90% CI) using modified IPI was 46.1% (38.6 to 53.2). At a median follow-up of 21 months, the overall response rate was 45.3% versus 35.9% and the median PFS was 10.8 months versus 9.8 months in the modified and standard IPI groups, respectively. Conclusion: Rates of grade 3-5 trAEs were significantly lower in patients receiving modified versus standard IPI. Although 12-month PFS did not meet the prespecified efficacy threshold compared with historical control, informal comparison of treatment groups did not suggest any reduction in efficacy with the modified schedule.
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu