ASCO 2019: Deferred Cytoreductive Nephrectomy Among Patients with Newly Diagnosed Metastatic Renal Cell Carcinoma Treated Initially with Sunitinib

Chicago, IL (UroToday.com) The CARMENA trial1 prompts more caution with upfront cytoreductive nephrectomy (CN) in patients with metastatic renal cell carcinoma (mRCC). Only 17% of patients in the sunitinib alone arm underwent deferred CN (dCN). Upfront systemic therapy has been proposed as a potential test to identify patients that might be suitable for CN. In this presented study, the authors sought to characterize outcomes of dCN after upfront sunitinib relative to sunitinib alone.

Patients from the International mRCC Database Consortium (IMDC) diagnosed between 2006 and 2018 with mRCC receiving upfront sunitinib were included in this study. All CNs done after initial sunitinib were included, excluding CNs performed after sunitinib failure. The outcomes that were explored included overall survival (OS), and treatment failure-free survival (TFFS). Importantly, dCN was analyzed as a time-varying covariate to account for immortal time bias. A subset analysis was also performed for patients with the best response as stable disease, partial response, or complete response.

A total of 708 patients were included, of whom 53 (7.5%) underwent dCN at a median of 6.5 months (IQR 3.5,10.5) from diagnosis. Patients in the dCN group were more likely to have better Karnofsky performance status (KPS), intermediate IMDC risk, fewer metastatic sites, and response to upfront sunitinib, as seen in Table 1.

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There were 604 deaths during a median follow-up of 63 months. The median OS and TTF with dCN compared to without dCN were 43.5 and 19.8 months vs. 9.4 and 4.3 months, respectively. When examining the multivariable analysis, dCN remained significantly associated with OS (HR 0.45, 95%CI 0.31-0.65; p<0.001) but not TFFS (HR 0.73, 95%CI 0.52-1.01; p=0.056) (Table 2). Figure 1 demonstrates the Kaplan-Meier curve for all patients, while Figure 2 shows the Kaplan-Meier curve for the subset of patients with stable disease, partial response, or complete response. In all curves, the dCN patients did better than those who received sunitinib alone.

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The authors concluded that patients who received dCN were carefully selected and achieved long OS. It is imperative that optimal selection criteria be identified and confirmation of the role of dCN in a clinical trial is required.

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Presented by: Bimal Bhindi, FRCS, MDCM, MSc, Urologic Oncologist, University of Calgary, Calgary, Alberta, Canada

Written by: Hanan Goldberg, MD, Urologic Oncology Fellow (SUO), University of Toronto, Princess Margaret Cancer Centre @GoldbergHanan at the 2019 ASCO Annual Meeting #ASCO19, May 31- June 4, 2019, Chicago, IL USA

References:
  1. Mejean A, et al. "Sunitinib Alone or after Nephrectomy in Metastatic Renal-Cell Carcinoma." New England Journal of Medicine. 2018. DOI: 10.1056/NEJMoa1803675.
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