A phase II trial of nivolumab followed by ipilimumab and nivolumab in advanced non-clear-cell renal cell carcinoma.

Autor: Conduit C; Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP), Sydney, NSW, Australia., Davis ID; Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP), Sydney, NSW, Australia.; Eastern Health Clinical School, Monash University, Box Hill, VIC, Australia.; Eastern Health, Melbourne, VIC, Australia., Goh JC; Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP), Sydney, NSW, Australia.; Royal Brisbane and Women's Hospital, Herston, QLD, Australia., Kichenadasse G; Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP), Sydney, NSW, Australia.; Flinders Centre for Innovation in Cancer, Flinders Medical Centre, Bedford Park, SA, Australia., Gurney H; Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP), Sydney, NSW, Australia.; Macquarie University, Sydney, NSW, Australia., Harris CA; Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP), Sydney, NSW, Australia.; St George Hospital Cancer Care Centre, Kogarah, NSW, Australia.; University of NSW South Wales, Sydney, NSW, Australia., Pook D; Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP), Sydney, NSW, Australia.; Monash Health, Melbourne, VIC, Australia., Krieger L; Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP), Sydney, NSW, Australia.; GenesisCare North Shore, St Leonards, NSW, Australia., Parnis F; Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP), Sydney, NSW, Australia.; Adelaide Cancer Centre, Kurralta Park, SA, Australia., Underhill C; Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP), Sydney, NSW, Australia.; Border Medical Oncology Research Unit, Albury Wodonga Regional Cancer Centre, East Albury, NSW, Australia.; Rural Medical School, Albury Campus, University of New South Wales, Albury-Wodonga, NSW, Australia., Adams D; Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP), Sydney, NSW, Australia.; Macarthur Cancer Therapy Centre, Campbelltown, NSW, Australia., Roncolato F; Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP), Sydney, NSW, Australia.; Macarthur Cancer Therapy Centre, Campbelltown, NSW, Australia.; NHMRC Clinical Trials Centre, University of Sydney, Camperdown, NSW, Australia., Joshua A; Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP), Sydney, NSW, Australia.; St Vincent's Hospital Sydney, Darlinghurst, NSW, Australia., Ferguson T; Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP), Sydney, NSW, Australia.; Fiona Stanley Hospital, Perth, WA, Australia., Prithviraj P; Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP), Sydney, NSW, Australia.; Ballarat Oncology and Haematology Services, Ballarat, VIC, Australia., Morris M; Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP), Sydney, NSW, Australia.; Sunshine Coast University Hospital, Birtinya, QLD, Australia., Harrison M; Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP), Sydney, NSW, Australia.; Royal Prince Alfred Hospital, Hunters Hill, NSW, Australia., Begbie S; Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP), Sydney, NSW, Australia.; North Coast Cancer Institute, Port Macquarie Base Hospital, Port Macquarie, NSW, Australia., Hovey E; Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP), Sydney, NSW, Australia.; Nelune Comprehensive Cancer Centre, Prince of Wales Hospital, Randwick, Sydney, NSW, Australia.; Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia., George M; Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP), Sydney, NSW, Australia.; Northwest Cancer Centre, Tamworth Hospital, Tamworth, NSW, Australia., Liow EC; Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP), Sydney, NSW, Australia.; Monash Health, Melbourne, VIC, Australia., Link EK; Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP), Sydney, NSW, Australia.; Centre for Biostatistics and Clinical Trials (BaCT), Peter MacCallum Cancer Centre, The University of Melbourne, Melbourne, VIC, Australia., McJannett M; Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP), Sydney, NSW, Australia., Gedye C; Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP), Sydney, NSW, Australia.; Calvary Mater Newcastle, Waratah, NSW, Australia.
Jazyk: angličtina
Zdroj: BJU international [BJU Int] 2024 Feb; Vol. 133 Suppl 3, pp. 57-67. Date of Electronic Publication: 2023 Nov 20.
DOI: 10.1111/bju.16190
Abstrakt: Objective: To evaluate the efficacy of sequential treatment with ipilimumab and nivolumab following progression on nivolumab monotherapy in individuals with advanced, non-clear-cell renal cell carcinoma (nccRCC).
Materials and Methods: UNISoN (ANZUP1602; NCT03177239) was an open-label, single-arm, phase 2 clinical trial that recruited adults with immunotherapy-naïve, advanced nccRCC. Participants received nivolumab 240 mg i.v. two-weekly for up to 12 months (Part 1), followed by sequential addition of ipilimumab 1 mg/kg three-weekly for four doses to nivolumab if disease progression occurred during treatment (Part 2). The primary endpoint was objective tumour response rate (OTRR) and secondary endpoints included duration of response (DOR), progression-free (PFS) and overall survival (OS), and toxicity (treatment-related adverse events).
Results: A total of 83 participants were eligible for Part 1, including people with papillary (37/83, 45%), chromophobe (15/83, 18%) and other nccRCC subtypes (31/83, 37%); 41 participants enrolled in Part 2. The median (range) follow-up was 22 (16-30) months. In Part 1, the OTRR was 16.9% (95% confidence interval [CI] 9.5-26.7), the median DOR was 20.7 months (95% CI 3.7-not reached) and the median PFS was 4.0 months (95% CI 3.6-7.4). Treatment-related adverse events were reported in 71% of participants; 19% were grade 3 or 4. For participants who enrolled in Part 2, the OTRR was 10%; the median DOR was 13.5 months (95% CI 4.8-19.7) and the median PFS 2.6 months (95% CI 2.2-3.8). Treatment-related adverse events occurred in 80% of these participants; 49% had grade 3, 4 or 5. The median OS was 24 months (95% CI 16-28) from time of enrolment in Part 1.
Conclusions: Nivolumab monotherapy had a modest effect overall, with a few participants experiencing a long DOR. Sequential combination immunotherapy by addition of ipilimumab in the context of disease progression to nivolumab in nccRCC is not supported by this study, with only a minority of participants benefiting from this strategy.
(© 2023 BJU International.)
Databáze: MEDLINE
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