J O U R N A L C L U B Essential Peer-Reviewed Reading in Kidney Cancer The peer-reviewed articles summarized in this section were selected by the Editor-in-Chief, Robert A. Figlin, MD, for their timeliness, importance, relevance, and potential impact on clinical practice or translational research. Systemic Therapy for non-clear cell renal cell carcinoma. Zhang T, Gong J, Maia MC, et al. Am Soc Clin Oncol Educ Book. 2017; 37:337-342. Summary: Little improvement has been made in the management of metastatic non-clear cell RCC (nccRCC). Nonclear cell disease is an umbrella term that encompasses multiple biologically distinct entities, including but not limited to papillary, chromophobe, and sarcomatoid RCC. To date, prospective studies have largely explored treatments for ccRCC (e.g., VEGF- and mTOR-directed therapies) in trials that aggregate non-clear cell histologies. However, the studies do not acknowledge the varying biology of each non-clear cell subtype. Conclusion: Emerging studies in nccRCC should examine individual histologies and apply biologically relevant therapies. An example of this is SWOG 1500, a randomized phase II study that will compare a VEGF-inhibitor to one of three MET-directed therapies in patients with metastatic papillary RCC. Until the biologic diversity of nccRCC is appreciated, outcomes are likely to remain dismal. Metastatic chromophobe renal cell carcinoma treated with targeted therapies: A Renal Cross Channel Group study. Colomba E, Le Teuff G, Eisen T, et al. Eur J Cancer. 2017; 23;80:55-62 Summary: Treatment of non-clear cell renal cell carcinoma (RCC) remains controversial despite several recent prospective studies of targeted therapies (TT). Often Vascular Endothelial growth Factor (VEGF) and Mammalian Target of Rapamycin (mTOR) inhibitors are used, extrapolating the data from use of these agents in clear cell RCC. This study performed a retrospective data analysis within the Renal Cross Channel Group to determine metastatic chromophobe RCC (mChRCC) outcomes in the TT era. The end-points were overall response, overall survival (OS) and time to treatment failure (TTF). The two latter were estimated using the Kaplan-Meier method. The study included 91 mChRCC patients from 26 centers. Median follow-up from the date of first metastasis was 6.1 years (range: 0-13.9). Median OS was 37.9 months from the diagnosis of metastatic disease. Among the 61 patients who received TT, 50 (82%) were treated with anti-angiogenic (AA) and 11 with mTOR inhibitors. Median TTF and OS in patients receiving a first line of AA was 8.7 months and 22.9 months vs 1.9 months and 3.2 months with mTOR inhibitors, respectively. A stratified log-rank test compared AA and mTOR inhibitors TT, while controlling the effect of the International Metastatic RCC Database Consortium risk group and no significant difference between AA and mTOR inhibitors was observed for TTF (P = 0.26) or for OS (P = 0.55). Conclusion: This report, the largest retrospective cohort of patients with mChRCC treated with TT, found no significant difference between AA and mTOR inhibitors for TTF and OS. Collecting duct carcinoma of the kidney: Disease characteristics and treatment outcomes from the National Cancer Database. Sui W, Matulay JT, Robins DJ, et al. Urol Oncol. 2017 May 8; pii: S1078-1439(17)30179-5. Summary: The National Cancer Database was queried for all cases of CDRCC and clear cell renal cell carcinoma (CCRCC) from 2004 to 2013. After removing patients with other cancer diagnoses, the analytic cohort was composed of 201,686 CCRCC and 577 CDRCC cases. Kaplan-Meier and cox proportional hazards analysis were employed to model survival. Compared to CCRCC, patients with CDRCC presented with higher grade stage, node positive, and metastatic disease (70.7% vs. 30.0% with metastasis; P<0.001). Overall median survival for CDRCC was 13.2 months for CCRCC. Increasing T stage, high-grade disease, and metastasis were predictors of mortality. Of 184 patients with metastatic CDRCC, 113 underwent cytoreductive nephrectomy (CNx) whereas the rest were treated with chemo/radiation or observed. Survival outcomes were improved in patients who received both CNx with chemo/radiation compared to CNx alone or chemo/radiation alone. Conclusion: CDRCC is an aggressive subtype of RCC. Median survival is 13 months after diagnosis, drastically lower than for CCRCC. More than 70% of patients have a metastatic disease at diagnosis. Chemo/radiation in addition to CNx is associated with a survival benefit over single mode therapy. Multicenter evaluation of the tolerability of combined treatment with PD-1 and CTLA-4 immune checkpoint inhibitors and palliative radiation therapy. Bang A, Whilhite TJ, Pike LRG, et al. Int J Radiat Oncol Biol Phys. 2017 Jun 1;98(2):344-351. Summary: Records from patients with metastatic nonsmall cell lung cancer, melanoma, or renal cell cancer who received at least 1 cycle of a CTLA-4 or PD-1 inhibitor and radiation were retrospectively reviewed. Immune-related adverse events, defined using Common Terminology Criteria for Adverse Events version 4.0, were tabulated in relation to treatment variables, and associations with 36 Kidney Cancer Journal (continued on page 52)
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