Optimized Management of Nivolumab and Ipilimumab in Advanced Renal Cell Carcinoma: A Response-Based Phase II Study (OMNIVORE)
| Autor: | Rana R. McKay, Lauren C. Harshman, David F. McDermott, Benjamin L. Maughan, Tracy L. Rose, Christos Kyriakopoulos, Bradley Alexander McGregor, Toni K. Choueiri, Walter M. Stadler, Yousef Zakharia, David A. Braun, Xiao Wei, Wanling Xie |
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| Rok vydání: | 2020 |
| Předmět: |
Adult
Male Cancer Research Phases of clinical research Ipilimumab 03 medical and health sciences 0302 clinical medicine Renal cell carcinoma Antineoplastic Combined Chemotherapy Protocols Humans Medicine Carcinoma Renal Cell Immune Checkpoint Inhibitors Aged business.industry ORIGINAL REPORTS Middle Aged medicine.disease Immune checkpoint Blockade Nivolumab Oncology 030220 oncology & carcinogenesis Cancer research Female business 030215 immunology medicine.drug |
| Zdroj: | J Clin Oncol |
| ISSN: | 1527-7755 0732-183X |
| Popis: | PURPOSE 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 ). METHODS 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). RESULTS 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. CONCLUSION 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. |
| Databáze: | OpenAIRE |
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