Vasudev, N.S. orcid.org/0000-0001-8470-7481, Ainsworth, G. orcid.org/0000-0002-9952-8440, Brown, S. orcid.org/0000-0002-7975-7537 et al. (24 more authors) (2023) Standard versus modified ipilimumab, in combination with nivolumab, in advanced renal cell carcinoma: a randomized phase II trial (PRISM). Journal of Clinical Oncology. JCO2300236. ISSN 0732-183X
Abstract
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.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2023 by American Society of Clinical Oncology. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives licence (https://creativecommons.org/licenses/by-nc-nd/4.0/) |
Keywords: | Biomedical and Clinical Sciences; Clinical Sciences; Oncology and Carcinogenesis; Clinical Research; Kidney Disease; Clinical Trials and Supportive Activities; Cellular and gene therapies; Evaluation of treatments and therapeutic interventions; Pharmaceuticals; Cancer |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > School of Medicine and Population Health |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 17 Nov 2023 15:05 |
Last Modified: | 17 Nov 2023 15:05 |
Status: | Published |
Publisher: | American Society of Clinical Oncology (ASCO) |
Refereed: | Yes |
Identification Number: | 10.1200/jco.23.00236 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:205491 |