272 COMBINED IMMUNOCHEMOTHERAPY IN SELECTED PATIENTS WITH METASTATIC RENAL CELL CARCINOMA: HLA CLASS II GENOTYPE CAN HELP TO PREDICT RESPONSE TO THERAPY

e17100 Background: Despite extensive work to characterize genomic alterations (GAs) in metastatic renal cell carcinoma (mRCC), GAs are not currently used for treatment sequencing or selection. Circulating tumor DNA (ctDNA) in both blood and urine may elucidate potential mRCC biomarkers through a minimally invasive approach. We aimed to validate previous blood-based ctDNA studies (Pal et al Eur Urol 2017) and compare detection rates of clinically relevant GAs in plasma and urine. Methods: From a single institution, patients (pts) with mRCC were recruited to provide a plasma and urine specimen. ctDNA next-generation sequencing was performed using an investigational 120-gene panel, and we limited our assessment to 7 GAs with biological relevance in RCC ( VHL, MTOR, PIK3CA, TSC2, MET, AKT1, TSC1). Further, only pathogenic alterations previously recognized in RCC and cited in the Catalogue of Somatic Mutations in Cancer (COSMIC) database were considered. Clinicopathologic variables, treatment type and response to therapy were collected from an institutional mRCC patient database. Concordance analysis was performed at the gene level between blood and urine using previously published approaches (Chae et al Oncotarget 2016). Results: 50 pts (40M:10F) were enrolled with a median age of 65. 40 pts (80%) had clear cell histology, while the remainder were papillary (12%), chromophobe (4%) or other (4%). Pts received a median of 1 line of therapy (range, 0-7). GAs were identified in 45 pts (90%) in blood and in 45 pts (90%) in urine . Applying the above criteria, the most frequently observed GAs in blood specimens were TSC2 (9%), MTOR (4%), and VHL (2%). The most frequently observed GAs in urine were VHL (4%) and MTOR (2%). The rate of concordance between blood- and urine-detected GAs was 93%. Of pts bearing mTOR pathway alterations in blood or urine, 3 received everolimus-based therapy. All 3 pts remain on therapy at 10.4, 13.8 and 14.0 months, respectively. Conclusions: Biologically relevant GAs can be detected in pts with mRCC using blood and urine. Our methodology showed high concordance between both platforms. Consistent with prior reports, ctDNA assessment of pts with pretreated mRCC shows a higher frequency of TOR pathway alterations and a lower frequency of VHL mutation.

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Heterozygosity Or Homozygosity For 2 HLA Class II Haplotypes Predict Favorable Outcomes For Renal Cell Carcinoma Treated With Cytokine Therapy

The Journal of Urology ◽

10.1097/01.ju.0000065810.80617.f4 ◽

2003 ◽

Vol 169 (6) ◽

pp. 2084-2088 ◽

Cited By ~ 9

Author(s):

JULIE A. ELLERHORST ◽

WILLIAM H. HILDEBRAND ◽

JOSHUA W. CAVETT ◽

MARCELO A. FERNANDEZ-VINA ◽

SHERIE HODGES ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Class Ii ◽

Hla Class Ii ◽

Cytokine Therapy

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Cytoreductive Nephrectomy Following Immunotherapy-Base Treatment in Metastatic Renal Cell Carcinoma: A Case Series and Review of Current Literature

Current Oncology ◽

10.3390/curroncol28030178 ◽

2021 ◽

Vol 28 (3) ◽

pp. 1921-1926

Author(s):

Scott J. Dawsey ◽

Steven C. Campbell ◽

Moshe C. Ornstein

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Metastatic Renal Cell Carcinoma ◽

Renal Cell ◽

Case Series ◽

Complete Response ◽

Response To Therapy ◽

Cytoreductive Nephrectomy ◽

Cell Renal Cell Carcinoma ◽

Treatment Paradigm

The role and timing of cytoreductive nephrectomy in patients with metastatic renal cell carcinoma receiving immunotherapy-based regimens is unclear. However, the ability to achieve a complete response for metastatic renal cell carcinoma likely requires a nephrectomy at some point during treatment. Here we present a case series of three patients with metastatic clear-cell renal-cell carcinoma who received front-line immunotherapy-based treatment and subsequently underwent a cytoreductive nephrectomy. All three patients had a complete response to therapy and have subsequently remained off systemic therapy for a median of 531 days (range, 476–602). We also review the limited literature in this setting and highlight ongoing clinical trials. Although the role of cytoreductive nephrectomy in patients with metastatic renal cell carcinoma receiving immunotherapy-based treatment is uncertain, a subset of patients will benefit from either an immediate or deferred cytoreductive nephrectomy. Ongoing trials are underway to further determine how to incorporate cytoreductive nephrectomy into the treatment paradigm for patients with metastatic renal cell carcinoma.

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ANALYSIS OF IMMUNE RESPONSE TO TUMOR SPECIFIC ANTIGEN RESTRICTED TO HLA CLASS II ON RENAL CELL CARCINOMA AND ITS RECOGNISION MECHANISM

The Japanese Journal of Urology ◽

10.5980/jpnjurol1989.93.457 ◽

2002 ◽

Vol 93 (3) ◽

pp. 457-462

Author(s):

Saori Nishijima ◽

Kimio Sugaya ◽

Yoshihide Ogawa ◽

Hideki Mukouyama ◽

Katsumasa Shimada

Keyword(s):

Renal Cell Carcinoma ◽

Immune Response ◽

Cell Carcinoma ◽

Renal Cell ◽

Specific Antigen ◽

Class Ii ◽

Hla Class Ii ◽

Tumor Specific Antigen

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Association between primary tumor protein expression and response to sunitinib in patients with metastatic renal cell carcinoma.

Journal of Clinical Oncology ◽

10.1200/jco.2015.33.7_suppl.450 ◽

2015 ◽

Vol 33 (7_suppl) ◽

pp. 450-450

Author(s):

Moshe Chaim Ornstein ◽

Vlado Knezevic ◽

Brian I. Rini ◽

Ulka N. Vaishampayan

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Metastatic Renal Cell Carcinoma ◽

Primary Tumor ◽

Renal Cell ◽

Objective Response ◽

Large Degree ◽

Response To Therapy ◽

Caix Expression ◽

Tumor Expression

450 Background: Sunitinib is FDA-approved and widely used as frontline treatment for metastatic renal cell carcinoma (mRCC), but there is a large degree of variability in patient (pt) response to therapy. The association of baseline primary tumor expression of multiple proteins and objective response to sunitinib was investigated. Methods: Primary tumor samples from clear cell mRCC pts treated with sunitinib as frontline therapy at two academic institutions were retrieved. Layered immunohistochemical (LIHC) assay which allow the detection of multiple biomarkers in a single tissue section was used to evaluate the expression of 8 proteins (VEGFR1, VEGFR2, p-mTOR, p-4E-BP1 S65, VEGF A, 4E-BP1, PDGFRb, CAIX) on tumor cells. Pts were characterized as Responders (Complete Responders (CR), Partial Responders (PR) and Stable diseases (SD)) or Non-Responders (NR) based on investigator-assessment. The 8 proteins were tested separately and the area under the receiver operator characteristic (ROC) curve (AUC) analysis was used to compare the predictive power of each biomarker and their combinations. Results: 38 pts were eligible for evaluation; 29 responders and 9 non-responders. Of the 8 biomarkers tested individually, only PDGFRb and CAIX were statistically significant in providing a predictive value for response to sunitinib. Of the different possible biomarker combinations, the combination of increased levels of CAIX expression and decreased 4E-BP1 expression provided the highest ROC AUC (0.9) for predicting response. When stable disease cases were removed from the responders group, in addition to CAIX and 4E-BP1, increased levels of PDGFRb expression predicted response (AUC was 0.889). Conclusions: Baseline primary tumor expression of CAIX and 4E-BP1 is associated with an objective response to sunitinib in pts with mRCC.

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Bone metastases affect prognosis but not effectiveness of third-line targeted therapies in patients with metastatic renal cell carcinoma

Canadian Urological Association Journal ◽

10.5489/cuaj.2377 ◽

2015 ◽

Vol 9 (7-8) ◽

pp. 263 ◽

Cited By ~ 5

Author(s):

Roberto Iacovelli ◽

Daniele Santini ◽

Mimma Rizzo ◽

Alessandra Felici ◽

Matteo Santoni ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Overall Survival ◽

Bone Metastases ◽

Cell Carcinoma ◽

Metastatic Renal Cell Carcinoma ◽

Targeted Therapies ◽

Renal Cell ◽

Response To Therapy ◽

Risk Of Death ◽

Risk Of Progression

Introduction: Treatment of metastatic renal cell carcinoma (mRCC) has improved with the use of targeted therapies, but bone metastases continue to be negative prognostic factor.Methods: Patients with mRCC treated with everolimus (EV) or sorafenib (SO) after two previous lines of targeted therapies were included in the analysis. Overall survival (OS) and progressionfree survival (PFS) were assessed based on the presence of bone metastases and type of therapy; they were also adjusted based on prognostic criteria.Results: Of the 233 patients with mRCC, 76 had bone metastases. Of the 233 patients, EV and SO were administered in 143 and 90 patients, respectively. Median OS was 10.4 months in patients with BMs and 17.4 months in patients without bone metastases (p = 0.002). EV decreased the risk of death by 18% compared to SO (adjusted hazard ratio [HR] 0.82, 95% confidence interval [CI] 0.74–0.91; p < 0.001), with comparable effects in patients with or without bone metastases. In the same manner, EV decreased the risk of progression by 12% compared to SO (adjusted HR 0.88, 95% CI 0.82–0.96; p = 0.002), but this difference was not significant in patients without bone metastases. The major limitations of the study are its retrospective nature, the heterogeneity of the methods to detect bone metastases, and the lack of data about patients treated with bisphosphonates.Conclusions: The relative benefit of targeted therapies in mRCC is not affected by the presence of bone metastases, but patients without bone metastases have longer response to therapy and overall survival.

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