Efficacy of Sunitinib and Sorafenib in Metastatic Papillary and Chromophobe Renal Cell Carcinoma

Purpose Sunitinib and sorafenib are novel tyrosine kinase inhibitors (TKIs) that have shown significant clinical activity in metastatic clear cell renal cell carcinoma (RCC). The activity of sunitinib and sorafenib in non–clear cell histologies has not been evaluated. Patients and Methods Clinical features at study entry and treatment outcomes were evaluated in patients with metastatic papillary RCC (PRCC) and chromophobe RCC (ChRCC) who received either sunitinib or sorafenib as their initial TKI treatment in five US and French institutions. Response rate and survival were documented. Fisher's exact test was used for categoric variables, and the Kaplan-Meier method was used to estimate survival. Results Fifty-three patients were included. The number of patients with papillary and chromophobe histologies was 41 (77%) and 12 (23%), respectively. Response rate, progression-free survival (PFS) time, and overall survival time for the entire cohort were 10%, 8.6 months, and 19.6 months, respectively. Three (25%) of 12 ChRCC patients achieved a response (two patients treated with sorafenib and one treated with sunitinib), and PFS was 10.6 months. Two (4.8%) of 41 PRCC patients achieved a response (both patients were treated with sunitinib). PFS for the whole cohort was 7.6 months. Sunitinib-treated PRCC patients had a PFS of 11.9 months compared with 5.1 months for sorafenib-treated patients (P < .001). Conclusion Patients with PRCC and ChRCC may have prolonged PFS from sunitinib and sorafenib, although clinical responses remain overall low in PRCC. Additional prospective trials with these agents in non–clear cell RCC will further clarify their use in the future.

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A convention-radiomics CT nomogram for differentiating fat-poor angiomyolipoma from clear cell renal cell carcinoma

Scientific Reports ◽

10.1038/s41598-021-84244-3 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Yanqing Ma ◽

Weijun Ma ◽

Xiren Xu ◽

Zheng Guan ◽

Peipei Pang

Keyword(s):

Risk Factors ◽

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Logistic Model ◽

Clear Cell ◽

Cell Renal Cell Carcinoma ◽

Entire Cohort ◽

Conventional Ct ◽

Radiomics Signature

AbstractThis study aimed to construct convention-radiomics CT nomogram containing conventional CT characteristics and radiomics signature for distinguishing fat-poor angiomyolipoma (fp-AML) from clear-cell renal cell carcinoma (ccRCC). 29 fp-AML and 110 ccRCC patients were enrolled and underwent CT examinations in this study. The radiomics-only logistic model was constructed with selected radiomics features by the analysis of variance (ANOVA)/Mann–Whitney (MW), correlation analysis, and Least Absolute Shrinkage and Selection Operator (LASSO), and the radiomics score (rad-score) was computed. The convention-radiomics logistic model based on independent conventional CT risk factors and rad-score was constructed for differentiating. Then the relevant nomogram was developed. Receiver operation characteristic (ROC) curves were calculated to quantify the accuracy for distinguishing. The rad-score of ccRCC was smaller than that of fp-AML. The convention-radioimics logistic model was constructed containing variables of enhancement pattern, VUP, and rad-score. To the entire cohort, the area under the curve (AUC) of convention-radiomics model (0.968 [95% CI 0.923–0.990]) was higher than that of radiomics-only model (0.958 [95% CI 0.910–0.985]). Our study indicated that convention-radiomics CT nomogram including conventional CT risk factors and radiomics signature exhibited better performance in distinguishing fp-AML from ccRCC.

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The Molecular Characteristics of Non-Clear Cell Renal Cell Carcinoma: What’s the Story Morning Glory?

International Journal of Molecular Sciences ◽

10.3390/ijms22126237 ◽

2021 ◽

Vol 22 (12) ◽

pp. 6237

Author(s):

Andrea Marchetti ◽

Matteo Rosellini ◽

Veronica Mollica ◽

Alessandro Rizzo ◽

Elisa Tassinari ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Kinase Inhibitors ◽

Clear Cell ◽

Treatment Algorithm ◽

Morning Glory ◽

Molecular Characteristics ◽

Cell Renal Cell Carcinoma ◽

Low Incidence

Non-clear cell renal cell carcinomas are a miscellaneous group of tumors that include different histological subtypes, each one characterized by peculiarity in terms of genetic alteration, clinical behavior, prognosis, and treatment response. Because of their low incidence and poor enrollment in clinical trials, alongside their heterogeneity, additional efforts are required to better unveil the pathogenetic mechanisms and, consequently, to improve the treatment algorithm. Nowadays, tyrosine kinase inhibitors, mTOR and MET inhibitors, and even cisplatin-based chemotherapy and immunotherapy are potential weapons that are still under evaluation in this setting. Various biomarkers have been evaluated for detecting progression and monitoring renal cell carcinoma, but more studies are necessary to improve this field. In this review, we provide an overview on the molecular characteristics of this group of tumors and the recently published trials, giving an insight into what might become the future therapeutic standard in this complex world of non-clear cell kidney cancers.

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Clinical activity of nivolumab in patients with non-clear cell renal cell carcinoma

Journal for ImmunoTherapy of Cancer ◽

10.1186/s40425-018-0319-9 ◽

2018 ◽

Vol 6 (1) ◽

Cited By ~ 61

Author(s):

Vadim S. Koshkin ◽

Pedro C. Barata ◽

Tian Zhang ◽

Daniel J. George ◽

Michael B. Atkins ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Clear Cell ◽

Clinical Activity ◽

Cell Renal Cell Carcinoma

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ASPEN: A randomized phase II trial of everolimus versus sunitinib in patients with metastatic non-clear cell renal cell carcinoma.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.tps4590 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. TPS4590-TPS4590

Author(s):

Andrew J. Armstrong ◽

Susan Halabi ◽

Tim Eisen ◽

Walter Michael Stadler ◽

Robert R Jones ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Clear Cell ◽

Case Series ◽

Progression Free Survival ◽

Clinical Activity ◽

Cell Renal Cell Carcinoma ◽

Therapeutic Decisions ◽

Undifferentiated Histology

TPS4590 Background: Currently no level 1 evidence exists to guide therapeutic decisions in patients with metastatic non-clear cell renal cell carcinoma. Case series and retrospective analyses suggest that strategies targeting either the VEGF or mTOR/TORC1 pathways have clinical activity in papillary, chromophobe, or poorly differentiated histologic subtypes. Methods: We are conducting an international, randomized phase 2 trial of patients with metastatic non-clear cell RCC; either papillary, chromophobe, or undifferentiated histology; any Motzer risk group; and who have had no prior systemic therapy. All patients contribute tissue to an international biorepository for correlative genomic, genetic, and protein biomarker studies, along with companion longitudinal plasma and urine angiome studies. Patients are randomized to either everolimus or sunitinib (1:1) at FDA approved dosing until progression. The primary endpoint is progression free survival. Trial status: Seventy-three out of a planned 108 subjects have been enrolled at the time of abstract submission: median age 64, 59 white, 10 black, 4 unknown race, and includes 42 papillary and 31 chromophobe/undifferentiated histologies, 49 men and 22 women. Accrual is anticipated to be completed by December 2013. Accrual distribution by country is currently 43 (USA), 27 (UK), and 3 (Canada). The first DSMB meeting was conducted after 40 subjects completed at least 6 months of therapy and concluded that there were no unexpected safety signals and that the study should proceed. Tissue (primary, some metastatic, urine, plasma, whole blood) has been collected on all patients to date through the Duke Center for Human Genetics Biorepository. Clinical trial information: NCT01108445.

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Response to systemic therapy in non-clear cell renal cell carcinomas: A systematic review and meta-analysis.

Journal of Clinical Oncology ◽

10.1200/jco.2014.32.4_suppl.425 ◽

2014 ◽

Vol 32 (4_suppl) ◽

pp. 425-425 ◽

Cited By ~ 5

Author(s):

Francisco Emilio Vera-Badillo ◽

Arnoud Templeton ◽

Alberto Ocana ◽

Paulo deGouveia ◽

Priya Aneja ◽

...

Keyword(s):

Systematic Review ◽

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Systemic Therapy ◽

Renal Cell ◽

Overall Response Rate ◽

Response Rate ◽

Clear Cell ◽

Meta Analysis ◽

Cell Renal Cell Carcinoma

425 Background: Clinical data supporting the efficacy of systemic therapy in non-clear cell renal cell carcinoma (non-ccRCC) are limited and based on retrospective analyses, expanded access programs and single arm phase II trials. Therefore the optimal treatment for this subgroup remains uncertain. Methods: A systematic review of electronic databases was conducted to identify publications evaluating the outcomes of patients with non-ccRCC (excluding those with sarcomatoid tumors) treated with different systemic approaches (immunotherapy, chemotherapy, targeted agents, small molecules). The primary endpoint was response rate and secondary endpoints were median progression free (PFS) and overall survival (OS). Where possible, data were pooled in a meta-analysis using the Mantel-Haenszel random-effect modeling. For studies comprising of unselected patients, outcomes of those with non-ccRCC were compared with clear cell renal cell carcinoma (ccRCC). Results: Forty-nine studies comprising 7,799 patients were included: 471 patients were enrolled on studies conducted exclusively in non-ccRCC and 7,328 patients on studies of unselected renal cell carcinoma. Among these, 903 (12%) had non-ccRCC and 6,425 (88%) had ccRCC. For non-ccRCC, overall response rate, median PFS and median OS were 9%, 7.9 and 13.4 months, respectively. By comparison, the overall response rate for ccRCC was 15% (Risk Ratio for response [RR] 0.67, 95% CI 0.52-0.86, p=0.002). This association was independent of type of treatment administered. Among the different novel agents (bevacizumab, lenalidomide, linefanib, sorafenib, sunitinib, pazopanib, everolimus and temsirolimus), sunitinib was significantly less efficacious in non-ccRCC than ccRCC (RR 0.56, 95% CI 0.42-0.72), but there was no significant difference in response rates for sorafenib (RR 0.64, 95% CI 0.31-1.35) or other agents (RR 1.10, 95% CI 0.50-2.44), However, confidence intervals were wide. Results of further analyses will be presented at the meeting. Conclusions: Patients with non-ccRCC have lower response rates than those with ccRCC, but the absolute difference between them is modest. Further study of targeted therapy in non-ccRCC is warranted.

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Clinical activity of PD1/PDL1 inhibitors in metastatic non-clear cell renal cell carcinoma (nccRCC).

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.6_suppl.482 ◽

2017 ◽

Vol 35 (6_suppl) ◽

pp. 482-482 ◽

Cited By ~ 7

Author(s):

Raphael Brandao Moreira ◽

Rana R. McKay ◽

Wanling Xie ◽

Daniel Yick Chin Heng ◽

Guillermo de Velasco ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Clear Cell ◽

Clinical Activity ◽

Significant Activity ◽

Cell Renal Cell Carcinoma ◽

Treatment Naïve ◽

Retrospective Multicenter Study

482 Background: PD1/PDL1 inhibitors have shown significant activity in the treatment of patients (pts) with metastatic clear cell renal cell carcinoma (ccRCC), but their activity in nccRCC is poorly characterized. Methods: We conducted a retrospective multicenter study of pts with metastatic nccRCC treated with PD1/PDL1 inhibitors. Baseline clinical parameters, overall response rate (ORR) by RECIST, time-to-treatment failure (TTF), and overall survival (OS) were summarized. Results: We identified 40 pts across 8 academic institutions. Fourteen (35%) had papillary histology, 10 (25%) chromophobe, 3 (8%) translocation, and 7 (18%) unclassified. Six (16%) had ccRCC with a sarcomatoid component > 30%. 20% had International Metastatic RCC Database Consortium (IMDC) favorable-risk disease, 60% intermediate, and 20% poor-risk. Ten (25%) were treatment-naïve and the majority received PD1/PDL1 monotherapy (n=30, 75%), while the remaining received a combination of PD1/PDL1 with anti-VEGF(R) or anti-CTLA4 therapy. ORR for the total cohort was 18% and 10% for PD1/PDL1 monotherapy pts (Table). With a median follow-up of 5.6 months, the overall median TTF was 4.7 months (2.9-15.9) and six-month OS was 81% (60-91%). Conclusions: PD1/PDL1 blockade resulted in some activity in pts with various nccRCC histologies. In the absence of available clinical trials, this data may support the use of PD1/PDL1 blocking agents in pts with nccRCC. [Table: see text]

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The Role of Everolimus in Renal Cell Carcinoma

Journal of Kidney Cancer and VHL ◽

10.15586/jkcvhl.2015.43 ◽

2015 ◽

Vol 2 (4) ◽

pp. 187-194

Author(s):

Malek Meskawi ◽

Roger Valdivieso ◽

Paolo Dell’Oglio ◽

Vincent Trudeau ◽

Alessandro Larcher ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Kinase Inhibitors ◽

Clear Cell ◽

Phase Iii ◽

Current Evidence ◽

Second Line ◽

Cell Renal Cell Carcinoma ◽

Line Therapy

Everolimus (RAD001) is an orally administered agent that inhibits the mammalian target of rapamycin serine-threonine kinase. A phase III pivotal trial on everolimus, published in 2008, provided the first evidence for the efficacy of sequential therapy for patients with metastatic clear cell renal cell carcinoma (RCC). In this study, everolimus was used after failure of one or several previous lines of therapy, and it demonstrated a 3-month survival benefit relative to placebo. Currently, based on the level 1 evidence, everolimus represents the molecule of choice for third-line therapy after failure of previous two tyrosine kinase inhibitors (TKIs). However, second-line use after failure of one TKI is challenged by two new molecules (nivolumab and cabozantinib), which proved to have better efficacy with similar toxicity profile. In non-clear cell metastatic RCC, the current evidence recommends everolimus as a second-line therapy after failure of previous first-line sunitinib.

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