Understanding the adverse event experience in the S-TRAC adjuvant trial of sunitinib for high-risk renal cell carcinoma

Until recently, the sole treatment for patients with nonmetastatic renal cell carcinoma (RCC) was nephrectomy followed by observation. As metastatic RCC (mRCC) remains largely incurable (5-year survival rate ∼12%), adjuvant treatment, with potential to prevent/delay disease recurrence, is needed. In November 2017, sunitinib was approved in the USA as the first adjuvant therapy for patients at high risk for recurrent RCC postnephrectomy based on results from the S-TRAC trial. Patients eligible for adjuvant treatment have no evidence of disease and may be less willing to tolerate side effects. Therefore, proactive adverse event management is critical for keeping patients on adjuvant treatment and requires understanding the subtle differences in the adverse event profile of sunitinib in the adjuvant versus metastatic RCC setting.

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The VENUSS prognostic model to predict disease recurrence following surgery for non-metastatic papillary renal cell carcinoma: development and evaluation using the ASSURE prospective clinical trial cohort

BMC Medicine ◽

10.1186/s12916-019-1419-1 ◽

2019 ◽

Vol 17 (1) ◽

Cited By ~ 5

Author(s):

Tobias Klatte ◽

Kevin M. Gallagher ◽

Luca Afferi ◽

Alessandro Volpe ◽

Nils Kroeger ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

High Risk ◽

Cell Carcinoma ◽

Renal Cell ◽

Prognostic Model ◽

Disease Recurrence ◽

Intermediate Risk ◽

Net Benefit ◽

Prognostic Groups ◽

Risk Patients

Abstract Background The current World Health Organization classification recognises 12 major subtypes of renal cell carcinoma (RCC). Although these subtypes differ on molecular and clinical levels, they are generally managed as the same disease, simply because they occur in the same organ. Specifically, there is a paucity of tools to risk-stratify patients with papillary RCC (PRCC). The purpose of this study was to develop and evaluate a tool to risk-stratify patients with clinically non-metastatic PRCC following curative surgery. Methods We studied clinicopathological variables and outcomes of 556 patients, who underwent full resection of sporadic, unilateral, non-metastatic (T1–4, N0–1, M0) PRCC at five institutions. Based on multivariable Fine-Gray competing risks regression models, we developed a prognostic scoring system to predict disease recurrence. This was further evaluated in the 150 PRCC patients recruited to the ASSURE trial. We compared the discrimination, calibration and decision-curve clinical net benefit against the Tumour, Node, Metastasis (TNM) stage group, University of California Integrated Staging System (UISS) and the 2018 Leibovich prognostic groups. Results We developed the VENUSS score from significant variables on multivariable analysis, which were the presence of VEnous tumour thrombus, NUclear grade, Size, T and N Stage. We created three risk groups based on the VENUSS score, with a 5-year cumulative incidence of recurrence equalling 2.9% in low-risk, 15.4% in intermediate-risk and 54.5% in high-risk patients. 91.7% of low-risk patients had oligometastatic recurrent disease, compared to 16.7% of intermediate-risk and 40.0% of high-risk patients. Discrimination, calibration and clinical net benefit from VENUSS appeared to be superior to UISS, TNM and Leibovich prognostic groups. Conclusions We developed and tested a prognostic model for patients with clinically non-metastatic PRCC, which is based on routine pathological variables. This model may be superior to standard models and could be used for tailoring postoperative surveillance and defining inclusion for prospective adjuvant clinical trials.

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Does presence of bone metastases portend worsened prognosis in metastatic renal cell carcinoma? Analysis of the REMARCC (Registry of MetAstatic RCC) database.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.6_suppl.655 ◽

2020 ◽

Vol 38 (6_suppl) ◽

pp. 655-655

Author(s):

Aaron Bradshaw ◽

Maria Carmen Mir ◽

Ricardo Autorino ◽

Andrea Minervini ◽

Maximilian Kriegmair ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

High Risk ◽

Bone Metastases ◽

Cell Carcinoma ◽

Renal Cell ◽

Prognostic Significance ◽

Multivariable Analysis ◽

Secondary Outcome ◽

Risk Category ◽

Metastatic Rcc

655 Background: The presence of brain metastases and bone metastases are generally understood to herald worsened prognosis following nephrectomy in patients with renal cell carcinoma (RCC). However, we sought to determine the effect of bone metastases on outcomes when already present at the time of cytoreductive radical nephrectomy (RN). Methods: Multicenter retrospective analysis of mRCC patients from the REgistry of MetAstatic RCC) REMARCC. Demographics, clinical variables, and outcomes were collected. Patients were stratified into low, medium, and high-risk groups based on Motzer Criteria, and analysis of impact of bone metastases was conducted within each group utilizing Kaplan-Meier analysis (KMA). Multivariable analysis (MVA) was utilized to identify predictors for outcomes. Primary outcome was progression-free survival (PFS) and secondary outcome was overall survival (OS). Results: A total of 447 patients (low- n=30, intermediate- n=208, and high-risk mRCC n=123, median follow-up 14.3 months) were included in the analysis. 124 patients had bone metastases and 323 had mRCC but no bone metastases. No significant demographic differences were noted between groups. KMA (Figure) showed no difference in median PFS for bone metastases vs. non bone metastases groups (6.1 vs. 6.4 months, p=0.973). KMA showed no difference in median OS (25.5 vs. 26.5 months, p=0.958). Similarly, stratification of patients into different Motzer risk categories did not demonstrate difference between bone vs. none bone mRCC for PFS and OS. MVA for PFS demonstrated increasing Motzer risk category (low risk referent vs. intermediate OR 1.89, p=0.006, high risk OR 3.24, p<0.001) as independent predictors. MVA for OS revealed increasing Motzer risk category (low ref, vs. intermediate OR 1.88, p=0.033, high risk 5.17, p<0.001) as being predictive. In neither analysis was presence of bone metastases significant (PFS p=0.690, OS p=0.268). Conclusions: Presence of bone metastases does not independently predict survival or oncologic outcomes in mRCC. While further validation is needed, the prognostic significance of bone metastases may be less than previously thought.

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