Journal article
Optimized Management of Nivolumab and Ipilimumab in Advanced Renal Cell Carcinoma: A Response-Based Phase II Study (OMNIVORE)
Journal of clinical oncology, Vol.38(36), pp.4240-4248
12/20/2020
DOI: 10.1200/JCO.20.02295
PMCID: PMC7768333
PMID: 33108238
Abstract
In this phase II response-adaptive trial, we investigated the rational application of immune checkpoint blockade in renal cell carcinoma (RCC; ClinicalTrials.gov identifier: NCT03203473).
We enrolled patients with metastatic RCC with no prior checkpoint inhibitor exposure. All patients received nivolumab alone with subsequent arm allocation based on response. Patients with a confirmed partial response (PR) or complete response (CR) within 6 months discontinued nivolumab and were observed (arm A). Patients with stable disease or progressive disease (PD) after no more than 6 months of nivolumab received two doses of ipilimumab (arm B). The primary endpoints were the proportion of patients with PR/CR at 1 year after nivolumab discontinuation (arm A) and proportion of nivolumab nonresponders who converted to PR/CR after ipilimumab (arm B).
Overall, 83 patients initiated treatment, of whom 96% had clear-cell histology, 51% were treatment naïve, and 67% had intermediate/poor-risk disease. Median follow-up was 19.5 months. Within 6 months, induction nivolumab resulted in a confirmed PR in 12% of patients (n = 10). Fourteen patients were not allocated to a study arm (seven because of toxicity, seven because of PD). Twelve patients (14%) were allocated to arm A and discontinued nivolumab, of whom five (42%; 90% CI, 18% to 68%) remained off nivolumab at ≥ 1 year. Of 57 patients (69%) allocated to arm B, two patients converted to a confirmed PR (4%; 90% CI, 1% to 11%), and no CRs were observed.
In this study, nivolumab followed by two doses of ipilimumab resulted in no CRs and a low PR/CR conversion. The number of patients evaluated for nivolumab discontinuation was too small to assess the value of this approach. Currently, our data do not support a response-adaptive strategy for checkpoint blockade in advanced RCC.
Details
- Title: Subtitle
- Optimized Management of Nivolumab and Ipilimumab in Advanced Renal Cell Carcinoma: A Response-Based Phase II Study (OMNIVORE)
- Creators
- Rana R McKay - University of California San DiegoBradley A McGregor - Dana-Farber Cancer InstituteWanling Xie - Dana-Farber Cancer InstituteDavid A Braun - Dana-Farber Cancer InstituteXiao Wei - Dana-Farber Cancer InstituteChristos E Kyriakopoulos - University of Wisconsin Carbone Cancer CenterYousef Zakharia - University of IowaBenjamin L Maughan - University of UtahTracy L Rose - University of North Carolina at Chapel HillWalter M Stadler - University of ChicagoDavid F McDermott - Beth Israel Deaconess Medical CenterLauren C Harshman - Dana-Farber Cancer InstituteToni K Choueiri - Dana-Farber Cancer Institute
- Resource Type
- Journal article
- Publication Details
- Journal of clinical oncology, Vol.38(36), pp.4240-4248
- DOI
- 10.1200/JCO.20.02295
- PMID
- 33108238
- PMCID
- PMC7768333
- NLM abbreviation
- J Clin Oncol
- ISSN
- 0732-183X
- eISSN
- 1527-7755
- Grant note
- K08 CA248967 / NCI NIH HHS P30 CA023100 / NCI NIH HHS P50 CA101942 / NCI NIH HHS P30 CA086862 / NCI NIH HHS
- Language
- English
- Date published
- 12/20/2020
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9984548379802771
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