Recent clinical data has renewed the debate regarding the role of CN for patients with metastatic RCC (mRCC). Metastatic S/R clear cell RCC is an aggressive variant that responds to ICI. However, the role of CN for metastatic S/R RCC in the ICI era has not been reported to date. Here, we evaluate CN outcomes in patients with metastatic S/R RCC treated with ICI.
We retrospectively reviewed the records of patients with mRCC with sarcomatoid, rhabdoid, or sarcomatoid plus rhabdoid dedifferentiation who had primary renal tumor in situ and received an ICI-based regimen at MD Anderson Cancer Center. Clinical endpoints of interest were time on ICI therapy and OS from ICI initiation. A directed acyclic graph was used to identify potential confounders to be adjusted in regression models. Hazard ratios (HR) and 95% confidence intervals (95% CI) were calculated using multivariable Cox regression models.
91 patients with metastatic S/R RCC received an ICI. At ICI initiation, 79.1% of patients had > 1 site of metastases, and 59.3% had International Metastatic RCC Database Consortium (IMDC) intermediate-risk disease. ICI was given as first-line treatment in 67.0% of patients, and the most frequent ICI used was nivolumab plus ipilimumab (42.9%), followed by PD-1 inhibitor monotherapy (29.7%). The table shows results of multivariable analyses adjusting for mRCC epithelial histology, IMDC risk group, and number of prior treatments. Patients who underwent a delayed or upfront CN had longer OS and time on ICI therapy than those without a nephrectomy. Table: 678P
|Nephrectomy status||Median time on ICI (months)||HR (95% CI)||P value||Median OS from ICI initiation (months)||HR (95% CI)||P value|
|No nephrectomy (n=29)||5.1||-||-||14.0||-||-|
|Cytoreductive nephrectomy (n=62)||7.7||0.59 (0.35-0.99)||0.046||29.0||0.54 (0.29-0.99)||0.048|
CN was independently associated with improved outcomes compared to not receiving a nephrectomy in patients with S/R RCC, with the strongest evidence found for time on ICI and weaker evidence for OS benefit. This hypothesis-generating study suggests that CN should be considered in select patients with S/R RCC who respond to ICI.
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P. Msaouel: Financial Interests, Personal, Advisory Board: Mirati Therapeutics; Financial Interests, Personal, Advisory Board: Bristol-Myers Squibb; Financial Interests, Personal, Advisory Board: Exelixis; Financial Interests, Personal, Invited Speaker, Non-branded educational talks: Exelixis; Financial Interests, Personal, Invited Speaker, Non-branded educational talks: Pfizer; Financial Interests, Institutional, Funding: Takeda; Financial Interests, Institutional, Funding: Bristol-Myers Squibb; Financial Interests, Institutional, Funding: Mirati Therapeutics; Financial Interests, Institutional, Funding: Gateway for Cancer Research. All other authors have declared no conflicts of interest.