720 patients were included in the final analysis. In terms of patient characteristics, all patients had clear cell mRCC. The majority of patients were men (77.4%), had prior nephrectomy (84.7%), and had an ECOG of 0 (85%). 22.4% of patients had already received two prior lines of therapy, and the majority of patients were intermediate and poor risk (81.7%). 12.3% of patients were found to have brain metastases per study screening protocol.
After a median of 20.9 months, the median duration of treatment was 5.2 months with 15% of patients still on treatment. The confirmed ORR was 21%, with the majority of those being partial responses and only 1.3% complete response. The median progression-free survival was 3.2 months and the 12-month survival rate was 69%. The curve begins to flatten out after 6 month – 6 month PFS was 35% and 12 month PFS was 23.8%.
Interestingly, 47% of patients were treated beyond progression. 59% of patients received an additional line of therapy and 22% died without any further therapy. In terms of overall survival, the median OS was 24.5 months with 69% of patients alive at one year and upon subgroup analysis, there was no difference in OS between the number of prior lines of therapy or presence of brain metastases. However, patients with poor performance status, prior everolimus, and poor renal function did have worse median OS.
OS correlated nicely with IMDC criteria with a median OS of 32 months, 25 months, and 10 months for favorable, intermediate, or poor risk disease, and separated out nicely even when broken down to the individual number of IMDC risk factors.
The best response was correlated with overall survival, with a median OS of 28.4 months for patients with stable disease and 13 months for those with initial progressive disease. PFS correlated with best response as well, with a median PFS of 27.8 months for those with a PR/CR.
This study confirms prior clinical trials in a real-world setting that nivolumab is active and safe in patients with clear cell RCC. In addition to the primary and secondary outcomes, two interesting points are described in this abstract. First, oncologists frequently treat beyond progression with nivolumab. Second, this study’s results bring to light what many oncologists have suspect regarding the relationship between response and immune toxicity, showing that patients who have some off-target effect of therapy may derive more benefit than those without any immune-mediated side effects.
Presented by: Laurence Albiges, MD, PhD, Head, Genitourinary Unit, Gustave Roussy Institute, Villejuif, France
Written by: Jason Zhu, MD. Fellow, Division of Hematology and Oncology, Duke University, @TheRealJasonZhu at the 2019 American Society of Clinical Oncology Genitourinary Cancers Symposium, (ASCO GU) #GU19, February 14-16, 2019 - San Francisco, CA
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- Motzer RJ, Escudier B, McDermott DF, et al. Nivolumab versus Everolimus in Advanced Renal-Cell Carcinoma. New England Journal of Medicine 2015;373:1803-13