Kidney Cancer - Volume 5, issue 3

Authors: Wilson, Lauren E. | Spees, Lisa | Pritchard, Jessica | Greiner, Melissa A. | Scales Jr, Charles D. | Baggett, Christopher D. | Kaye, Deborah | George, Daniel J. | Zhang, Tian | Wheeler, Stephanie B. | Dinan, Michaela A.

Article Type: Research Article

Abstract: BACKGROUND: Substantial racial and socioeconomic disparities in metastatic RCC (mRCC) have persisted following the introduction of targeted oral anticancer agents (OAAs). The relationship between patient characteristics and OAA access and costs that may underlie persistent disparities in mRCC outcomes have not been examined in a nationally representative patient population. METHODS: Retrospective SEER-Medicare analysis of patients diagnosed with mRCC between 2007–2015 over age 65 with Medicare part D prescription drug coverage. Associations between patient characteristics, OAA receipt, and associated costs were analyzed in the 12 months following mRCC diagnosis and adjusted to 2015 dollars. RESULTS: 2,792 patients …met inclusion criteria, of which 32.4%received an OAA. Most patients received sunitinib (57%) or pazopanib (28%) as their first oral therapy. Receipt of OAA did not differ by race/ethnicity or socioeconomic indicators. Patients of advanced age (> 80 years), unmarried patients, and patients residing in the Southern US were less likely to receive OAAs. The mean inflation-adjusted 30-day cost to Medicare of a patient’s first OAA prescription nearly doubled from $3864 in 2007 to $7482 in 2015, while patient out-of-pocket cost decreased from $2409 to $1477. CONCLUSION: Race, ethnicity, and socioeconomic status were not associated with decreased OAA receipt in patients with mRCC; however, residing in the Southern United States was, as was marital status. Surprisingly, the cost to Medicare of an initial OAA prescription nearly doubled from 2007 to 2015, while patient out-of-pocket costs decreased substantially. Shifts in OAA costs may have significant economic implications in the era of personalized medicine. Show more

Keywords: Renal cell carcinoma, oral anticancer agents, targeted therapy, chemotherapy, cost of care, health disparities

DOI: 10.3233/KCA-210119

Citation: Kidney Cancer, vol. 5, no. 3, pp. 115-127, 2021

Authors: Bhindi, Bimal | Bearrick, Elizabeth N. | Cheville, John C. | Lohse, Christine M. | Mason, Ross J. | Shah, Paras | Harrington, Susan | Zhang, Henan | Dong, Haidong | Boorjian, Stephen A. | Thompson, R. Houston | Leibovich, Bradley C.

Article Type: Research Article

Abstract: BACKGROUND: Bim (BCL-2-interacting mediator of cell death) is a downstream pro-apoptotic signaling molecule activated by the PD-1 pathway. OBJECTIVE: We sought to determine if Bim expression in peritumoral T-lymphocytes (PTLs) is associated with survival in patients with metastatic clear cell renal cell carcinoma (ccRCC). METHODS: Immunohistochemistry staining for Bim was performed on paraffin-embedded tumor tissue blocks from patients with metastatic ccRCC who underwent nephrectomy between 1990-2004. Associations of Bim expression with cancer-specific survival (CSS) and overall survival (OS) from date of metastasis were evaluated using multivariable Cox regression models, adjusting for age, sex, and metastases-score. …RESULTS: 525 patients with metastatic ccRCC, of whom 169 (32%) had metastases at time of nephrectomy were studied. After multivariable adjustment, high Bim expression remained associated with worse CSS (HR = 1.31; 95% CI 1.07–1.59; p = 0.008) and OS (HR = 1.28; 95% CI 1.06–1.55; p = 0.01). The interaction between Bim and PD-L1 was not statistically significant for CSS (p  = 0.68) or OS (p  = 0.57), suggesting that the associations between Bim and survival outcomes were not significantly different based on tumor PD-L1 expression. CONCLUSION: High Bim expression in PTLs at nephrectomy is prognostic of worse CSS and OS in patients with metastatic ccRCC, irrespective of tumor PD-L1 expression. The role of earlier PD-1/PD-L1-directed therapy warrants evaluation in these patients. Show more

Keywords: Kidney neoplasms, metastasis, nephrectomy, renal cell carcinoma

DOI: 10.3233/KCA-210116

Citation: Kidney Cancer, vol. 5, no. 3, pp. 129-135, 2021

Authors: Dall’Era, Marc | Lara Jr., Primo N.

Article Type: Article Commentary

DOI: 10.3233/KCA-200008

Citation: Kidney Cancer, vol. 5, no. 3, pp. 137-138, 2021

Authors: Ellis, Elizabeth E. | Messing, Edward

Article Type: Systematic Review

Abstract: BACKGROUND: Our goal is to review current literature regarding active surveillance (AS) of small renal masses (SRMs) and identify trends in survival outcomes, factors that predict the need for further intervention, and quality of life (QOL). METHODS: We performed a comprehensive literature search in PubMed and EMBASE and identified 194 articles. A narrative summary was performed in lieu of a meta-analysis due to the heterogeneity of selected studies. RESULTS: Seventeen articles were chosen to be featured in this review. Growth rate (GR) was not an accurate predictor of malignancy, although it was the characteristic most commonly …used to trigger delayed intervention (DI). The mean 5-year overall survival (OS) of all studies was 73.6% ±1.7% for AS groups. The combined cancer specific survival (CSS) for AS is 97.1% ±0.6%, compared to 98.6% ±0.4% for the primary intervention (PI) groups, (p  = 0.038). CONCLUSIONS: Short and intermediate-term data demonstrate that AS with the option for DI is a management approach whose efficacy (in terms of CSS) approaches that of PI at 5 years, is cost effective, and prevents overtreatment, especially in patients with significant comorbidities. Show more

Keywords: Carcinoma, renal cell, biopsy, prognosis, quality of life

DOI: 10.3233/KCA-210114

Citation: Kidney Cancer, vol. 5, no. 3, pp. 139-152, 2021

Authors: Shpilsky, Jason | Catalano, Paul J. | McDermott, David F.

Article Type: Systematic Review

Abstract: BACKGROUND: Combination or multi-agent therapy including immune checkpoint inhibitors has shifted the landscape of the treatment of advanced/metastatic renal cell carcinoma. There are several approved immune checkpoint inhibitor (ICI) combinations featuring antibodies against programmed cell death protein 1 (PD-1) receptor or its ligand 1 (PD-L1) combined with other immune checkpoint inhibitors, multi-targeted tyrosine kinase inhibitors (TKIs), or other agents active in renal cell carcinoma. OBJECTIVE: This study aims to compile the evidence of available first-line combination therapies compared to sunitinib monotherapy in advanced renal cell carcinoma. METHODS: A systematic literature search was conducted according to the …PRISMA statement to identify all randomized Phase III clinical trial data in previously untreated metastatic renal cell carcinoma featuring an immune checkpoint inhibitor combination compared against sunitinib. A two-stage selection process was utilized to determine eligible studies. Of a total of 124 studies and 94 additional abstracts, 6 studies were considered for final analysis. These studies were evaluated for progression free survival (PFS), overall survival (OS), Grade III or higher adverse events (AEs), objective response rate (ORR), and complete response rate (CRR). RESULTS: 6 studies with 5,121 patients met our search criteria. For OS, ICI combination therapy was favored over sunitinib with an estimated combined hazard ratio of 0.74 (0.67–0.81 95% CI). For PFS, ICI combination therapy was favored over sunitinib with an estimated combined hazard ratio of 0.65 (0.52–0.82, 95% CI). The combination of nivolumab and ipilimumab had the longest duration of response and less incidence of grade III or higher adverse events compared to the combination of anti-PD-1/PD-L1 with TKI. The combination of anti-PD-1/PD-L1 with TKI had higher rates of overall response and longer PFS than the combination of nivolumab/ipilimumab. CONCLUSIONS: This meta-analysis supports the recommendation of immune checkpoint inhibitor combination therapy over sunitinib monotherapy for previously untreated advanced renal cell carcinoma by virtue of improved PFS and OS. The choice of which ICI combination therapy to use may be guided by patient-specific characteristics including IMDC risk status, adverse effect profile, and need for early response. Show more

Keywords: Metastatic renal cell carcinoma, kidney cancer, immunotherapy, tyrosine kinase inhibitor, combination therapy, treatment sequencing

DOI: 10.3233/KCA-210120

Citation: Kidney Cancer, vol. 5, no. 3, pp. 153-163, 2021

Authors: Parikh, Mamta

Article Type: Other

DOI: 10.3233/KCA-210001

Citation: Kidney Cancer, vol. 5, no. 3, pp. 165-166, 2021