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.
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.
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.
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.
Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2023 Nov 06 [Epub ahead of print]
Naveen S Vasudev, Gemma Ainsworth, Sarah Brown, Lisa Pickering, Tom Waddell, Kate Fife, Richard Griffiths, Anand Sharma, Eszter Katona, Helen Howard, Galina Velikova, Anthony Maraveyas, Janet Brown, Carmel Pezaro, Mark Tuthill, Ekaterini Boleti, Amit Bahl, Bernadett Szabados, Rosamonde E Banks, Joanne Brown, Balaji Venugopal, Poulam Patel, Ankit Jain, Stefan N Symeonides, Paul Nathan, Fiona J Collinson, Thomas Powles
Leeds Institute of Medical Research at St James's, University of Leeds, St James's University Hospital, Leeds, United Kingdom., Clinical Trials Research Unit, University of Leeds, Leeds, United Kingdom., Royal Marsden Hospital, London, United Kingdom., Department of Medical Oncology, Christie Hospital, Manchester, United Kingdom., Addenbrooke's Hospital, Cambridge, United Kingdom., The Clatterbridge Cancer Centre, Liverpool, United Kingdom., Mount Vernon Cancer Centre, Middlesex, United Kingdom., Castle Hill Hospital, Hull, United Kingdom., Department of Oncology and Metabolism, University of Sheffield, Sheffield, United Kingdom., Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, United Kingdom., Department of Oncology, Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom., Royal Free London NHS Foundation Trust, London, United Kingdom., Bristol Haematology and Oncology Centre, University Hospitals Bristol and Weston NHS Foundation Trust, Bristol, United Kingdom., Barts Cancer Institute, Queen Mary University of London, London, United Kingdom., Institute of Cancer Sciences, University of Glasgow, Beatson West of Scotland Cancer Centre, Glasgow, United Kingdom., Division of Cancer & Stem Cells, School of Medicine, University of Nottingham, Nottingham, United Kingdom., The Royal Wolverhampton NHS Trust, Wolverhampton, United Kingdom., Edinburgh Cancer Centre, Western General Hospital, NHS Lothian, Edinburgh, United Kingdom.