Metastatic Renal Cell Carcinoma Database Research Articles

Interactive Data Visualization Tool for Patient-Centered Decision Making in Kidney Cancer.

Patients and providers often lack clinical decision tools to enable effective shared decision making. This is especially true in the rapidly changing therapeutic landscape of metastatic kidney cancer. Using the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) criteria, a validated risk prediction tool for patients with metastatic renal cell carcinoma, we created and user-tested a novel interactive visualization for clinical use. An interactive visualization depicting IMDC criteria was created, with the final version including data for more than 4,500 patients. Usability testing was performed with nonmedical lay-users and medical oncology fellow physicians. Subjects used the tool to calculate median survival times based on IMDC criteria. User confidence was surveyed. An iterative user feedback implementation cycle was completed and informed revision of the tool. The tool is available at CloViz-IMDC. Initially, 400 lay-users and 15 physicians completed clinical scenarios and surveys. Cumulative accuracy across scenarios was higher for physicians than lay-users (84% v 74%; P = .03). Eighty-three percent of lay-users and 87% of physicians thought the tool became intuitive with use. Sixty-eight percent of lay-users wanted to use the tool clinically compared with 87% of physicians. After revisions, the updated tool was user-tested with 100 lay-users and 15 physicians. Physicians, but not lay-users, showed significant improvement in accuracy in the updated version of the tool (90% v 67%; P = .008). Seventy-two percent of lay-users and 93% of physicians wanted to use the updated tool in a clinical setting. A graphical method of interacting with a validated nomogram provides prognosis results that can be used by nonmedical lay-users and physicians, and has the potential for expanded use across many clinical conditions.

Cabozantinib beyond progression improves survival in advanced renal cell carcinoma patients: the CABEYOND study (Meet-URO 21)

ABSTRACT Background Cabozantinib improves survival in metastatic renal cell carcinoma (mRCC) after prior antiangiogenics. The best treatment at disease progression (PD) is unknown. Being also a AXL/MET inhibitor, involved in acquired resistance, we hypothesized a prolonged tumor growth control in patients continuing cabozantinib despite PD. Research Design and Methods This retrospective multicenter study enrolled patients receiving cabozantinib after the first line between 2014 and 2020. We compared patients maintaining cabozantinib after first PD due to clinical benefit and good tolerability with those who changed therapy. The postprogression survival (PPS) of both was our primary endpoint. Results We analyzed 89 patients: 45 received cabozantinib beyond PD and 44 switched therapy. 40.4%, 31.5%, and 28.1% of patients received 1, 2, or >2 prior treatment, respectively. 84.3% were intermediate-poor International Metastatic Renal Cell Carcinoma Database risk. Patients continuing cabozantinib showed a higher response rate to cabozantinib before PD (46.7% vs 25%, p = 0.03) and were more heavily pretreated. Continuing cabozantinib showed a significantly longer PPS compared with switching therapy (median PPS 16.9 vs 13.2 months, HR 0.66, 95%CI 0.48–0.92, p = 0.011). Conclusions We observed longer PPS in patients continuing cabozantinib beyond PD, suggesting that this could be an effective option.

Assessment of prognostic factors in previously treated Japanese patients with metastatic renal cell carcinoma who received nivolumab: An observational multi-institute study.

The aim of the present study was to evaluate the prognosis of Japanese patients with metastatic renal cell carcinoma (mRCC) receiving nivolumab and to identify factors predicting the overall survival (OS) in this cohort of patients. This study retrospectively assessed the outcomes of 77 consecutive Japanese patients with mRCC who were treated using either 1 or 2 molecular-targeted agents followed by nivolumab in routine clinical practice. The best responses to nivolumab observed were as follows: Complete response in 3 patients, partial response in 27, stable disease in 33 and progressive disease in 14; therefore, the objective response rate in the 77 patients was 39.0%. During the median follow-up period of 11 months after the introduction of nivolumab, the median progression-free survival and OS were 7 months and not reached, respectively. On multivariate analysis of several parameters, age, Karnofsky Performance Status (KPS) and neutrophil counts were demonstrated to be independently associated with OS in the 77 patients. By dividing these patients into 3 groups according to 3 risk factors, it was possible to stratify the OS; however, the International Metastatic Renal Cell Carcinoma Database Consortium model was unable to classify the OS. These results suggested that age, KPS and neutrophil counts were useful predictors of OS in previously treated patients with mRCC who received nivolumab.

Risk Stratification and Treatment Algorithm of Metastatic Renal Cell Carcinoma.

Systemic therapy for metastatic renal cell carcinoma has continuously evolved over the last two decades. Significant improvements in overall survival and quality of life of patients with advanced disease have been observed. With the approval of combination therapies with PD(L)-1 immune checkpoint inhibitors (ICI) as first-line therapy in 2019, the previous standard VEGFR-TKI monotherapy has been replaced as the primary treatment option. In addition to immunotherapy with nivolumab and ipilimumab, three VEGFR-TKI/ICI combinations are now approved. Therapy selection should be preceded by risk stratification using defined criteria from the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC). Clinical parameters, as well as detailed patient counseling on differences in the efficacy profile (response rate, long-term progression-free survival), potential side effects, and impact on quality of life, are of key importance in the individual treatment decision.

Experience of using 1<sup>st</sup> line combination immunotherapy in patients with metastatic renal cell carcinoma

The study objective is to evaluate effectiveness and tolerability of 1st line combination immuno-oncological therapy with nivolumab and ipilimumab in patients with metastatic renal cell carcinoma (mRCC) in clinical practice.Materials and methods. The study included 38 patients with mRCC who received combination immunotherapy between July of 2019 and September of 2021. Median follow-up duration was 8 (2-25) months. Mean age of the patients was 58.3 (20-85) years. Previously 22 (57.9 %) patients underwent surgical treatment. Unfavorable physical status 2-3 per the ECOG scale was observed in 10 (26.3 %) patients. Clear-cell type of renal cell carcinoma was diagnosed in 34 (89.6 %) patients, non-clear-cell types in 4 (10.4 %). Sarcomatoid component in the tumor was detected in 8 (21.0 %) patients. G3-4 mRCC variant was verified in 16 (42.1 %) patients. Poor prognosis per the IMDC (International Metastatic Renal Cell Carcinoma Database Consortium) scale was identified in 16 (42.1 %) patients, intermediate -in 20 (52.6 %) patients. All 4 administrations of combination immunotherapy were received by 29 (76.3 %) patients.Results. For median follow-up duration of 8 (2-25) months, 23 (60.5 %) patients continue treatment, 15 (39.5 %) completed therapy with nivolumab and ipilimumab due to various reasons including progression in 11 (28.9 %), death in 2 (5.3 %), intolerable toxicity in 2 (5.3 %) cases. Median duration of combination immunotherapy was 9 (2-24) months. Subsequent antitumor therapy was administered to 3 (7.9 %) patients. During induction course immune-mediated adverse event (grade III-IV hepatitis) developed in 3 (7.9 %) patients. Adverse events were observed in 81.6 % of patients, including grade III-IV in 23.7 % of patients. Objective response was observed in 44.8 % of cases, complete response in 5.3 % of cases, partial response in 39.5 % of cases; controlled disease was achieved in 84.3 % of patients. Median progression-free survival and overall survival were 8 months.Conclusion. In our study despite large number of patients with poor prognosis and poorly differentiated tumors, 64.0 % of patients are alive and 60.5 % of patients continue treatment without disease progression after 18 months of combination immunotherapy. Progression-free survival was significantly affected by sarcomatoid component in the tumor, number of unfavorable factors per the IMDC scale, best response per RECIST 1.1; overall survival was significantly affected by sarcomatoid component in the tumor, sum of measurable lesions, number of unfavorable factors per the IMDC scale, best response per RECIST 1.1, and presence of symptomatic metastases in the brain.

Outcomes of Cytoreductive Nephrectomy for Patients with Metastatic Renal Cell Carcinoma: Real World Data from Canadian Centers

BackgroundTreatment options for metastatic renal cell carcinoma (mRCC) include cytoreductive nephrectomy (CN) and systemic therapy (ST). Results from the CARMENA and SURTIME trials suggest that CN before ST may not be the optimal treatment strategy for mRCC. ObjectiveTo use real-world data to evaluate and compare outcomes for patients with mRCC who underwent CN before, after, or without ST to those patients who only received ST. Design, setting, and participantsThe Canadian Kidney Cancer information system (CKCis) database was used to identify patients diagnosed with mRCC between January 2011 and April 2020. Only patients with synchronous disease, treated within 12 mo from their initial RCC diagnosis, with International Metastatic Renal Cell Carcinoma Database Consortium intermediate/high risk, and confirmed RCC histology were included. Outcome measurements and statistical analysisPatients were classified into four groups according to the initial treatment received for mRCC. Inverse probability of treatment weighting using propensity scores was used to balance the treatment groups. Cox proportional hazards models were used to assess the impact of CN after adjusting for potential confounding variables in the weighted cohorts. Results and limitationsA total of 788 patients were included in the study cohort. Of these 383 patients underwent CN before ST, 73 underwent CN after ST, 80 underwent CN only, and 252 patients received ST only. The median patient age was 63 yr and 73% of the cohort were men. In weighted analysis, the groups undergoing CN before ST (hazard ratio [HR] 0.65, 95% confidence interval [CI] 0.52–0.82) and CN after ST (HR 0.41, 95% CI 0.28–0.60) both had better survival compared to the ST only group. No survival benefit was observed for CN only compared to ST only, or for CN before ST compared to CN after ST. ConclusionsWe evaluated the association between different sequences of treatment with CN and survival in patients with mRCC using CKCis real world data. The results demonstrate that the selected patients who undergo CN, whether performed before or after ST, have an associated improvement in survival. Patient summaryTwo of the treatment options for metastatic kidney cancer are surgery and systemic therapy (chemotherapy or immunotherapy). We used data from the Canadian Kidney Cancer information system to determine whether there are differences in survival according to the sequencing of these treatments. Patients who had both surgery and systemic therapy, regardless of which treatment was first, had better survival than patients who only received systemic therapy.

Myocarditis as an immune-related adverse event following treatment with ipilimumab and nivolumab combination therapy for metastatic renal cell carcinoma: a case report

BackgroundImmune checkpoint inhibitors are new immunotherapy drugs globally used for many malignancies, including renal cell carcinoma. Myocarditis as an immune-related adverse event is rare but highly fatal, suggesting that its frequency may be higher than reported. This paper describes a case of myocarditis that developed asymptomatically following ipilimumab and nivolumab combination therapy for renal cell carcinoma.Case presentationA 71-year-old Asian man who presented to hospital with fever, fatigue, and weight loss of approximately 10 kg within 2 months was diagnosed with Xp.11.2 translocation renal cell carcinoma. Computed tomography revealed multiple lung masses, mediastinal lymph node enlargement, and a level II tumor thrombus reaching the inferior vena cava (cT3bN0M1; International Metastatic Renal Cell Carcinoma Database Consortium, poor risk). Ipilimumab/nivolumab combination therapy was started as induction therapy. The patient experienced acute interstitial nephritis as an immune-related adverse event after treatment initiation; however, a good response to steroid therapy was observed. The antitumor effect of the immunotherapy was notable. Although he experienced pulmonary embolism, it seemed asymptomatic and harmless; thus, a second infusion was introduced. From the eighth day, he demonstrated rapidly worsening cardiogenic shock with asymptomatic electrocardiographic changes and drastic drop in cardiac biomarkers, and a diagnosis of myocarditis as an immune-related adverse event was made. Although immediate methylprednisolone mini-pulse therapy followed by tapered prednisolone prevented mortality, extensive myocardial fibrosis with marked ejection fraction decline persisted as a sequela. Consequently, follow-up without treatment was instituted; however, much of the tumor response initially observed was maintained over several months.ConclusionPhysicians treating patients with immune checkpoint inhibitors should be aware of their potentially life-threatening cardiotoxic effects. This study emphasized the importance of a high index of suspicion, prompt diagnosis, and early intervention in patients who present with cardiac abnormalities and possible myocarditis after receiving immunotherapy.

Real-world outcomes in patients with metastatic renal cell carcinoma treated with first-line nivolumab plus ipilimumab.

305 Background: Nivolumab plus ipilimumab (NIVO+IPI), a first-in-class combination immunotherapy, was approved by the US Food and Drug Administration in April 2018 for the treatment of intermediate- or poor-risk advanced renal cell carcinoma (RCC), and the treatment paradigm has changed dramatically over the past few years. This real-world study examined treatment patterns and sequences, treatment response, safety, and survival outcomes with this novel first-line (1L) combination therapy among patients diagnosed with metastatic RCC (mRCC) in a community oncology practice setting. Methods: A retrospective analysis of the US Oncology Network’s iKnowMed medical data examined adult patients with an International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) prognosis of intermediate- or poor-risk clear cell mRCC who received 1L NIVO+IPI between April 1, 2018, and March 31, 2020. Baseline demographic and clinical characteristics, treatment patterns, and treatment sequence were examined descriptively. Overall survival (OS), progression-free survival (PFS), objective response rate (ORR), duration of response (DoR), time to treatment discontinuation (TTD), and time to treatment response (TTR) were analyzed using the Kaplan–Meier method. Treatment-related adverse events (TRAEs) and healthcare resource utilization were also analyzed. Results: A total of 193 adults with stage IV mRCC treated with 1L NIVO+IPI were identified. Median age (range) was 63 (30.0–89.0) years, 73.1% were male, 69.4% were white, 56.7% were IMDC intermediate risk, and 60.6% had a documented Eastern Cooperative Oncology Group performance status of 0 or 1. Median follow-up time (range) was 9.7 (0.1–24.7) months. Median PFS (95% CI) was 17.1 (12.6–21.2) months, and the 1-year landmark PFS rate was 58.3% (50.4–65.4). At 12 months, the OS rate (95% CI) was 75.4% (67.8–81.4). The ORR (95% CI) was 43.2% (34.6–52.1) among patients with a response assessment; the median TTR (range) was 2.8 (0.3–4.1) months and median DoR was not reached. Median TTD (95% CI) was 5.8 (4.5–7.5) months. Among the 63 (31.3%) patients who received second-line therapy, 50.8% received cabozantinib and 12.7% received pazopanib. TRAEs were reported in 47.2% of patients—the most frequently reported were fatigue (13.5%), rash (10.4%), diarrhea (6.7%), nausea (6.2%), colitis (3.6%), and pruritus (3.6%). The treatment-related hospitalization rate was 5.5% and the emergency department visit rate was 3.1%. Conclusions: This real-world study supports the clinical efficacy of 1L NIVO+IPI for patients with mRCC. Our findings also suggest that the NIVO+IPI combination was generally well tolerated in the real-world setting, with low rates of adverse events and healthcare resource utilization.

Safety and Efficacy of Tivozanib in First-Line mRCC: A Multicenter Compassionate-Use Study (Meet-Uro 16)

Introduction: Tivozanib is a potent and selective tyrosine kinase inhibitor of vascular endothelial growth factor receptor 1 (VEGFR-1), VEGFR-2, and VEGFR-3, recently approved in Europe for the first-line treatment of metastatic renal cell carcinoma (mRCC). Methods: Retrospective analysis of safety and activity of tivozanib administered at 1.34 mg daily (3 weeks on, 1 week off) within a compassionate-use program to patients with mRCC with no prior systemic treatment in Italy. Results: From August 2018 to April 2019, 64 patients have started tivozanib in 9 oncology units. The median age was 67.5 years (range 40–85), 62.5% males. According to International Metastatic Renal Cell Carcinoma Database Consortium criteria, 27.1% of patients were good prognosis, 57.6% intermediate, and 15.3% poor. Primary tumor had been removed in 71.9% of patients. Histology was clear cell 89%, papillary 4.7%, and unclassified 6.3%. The response rate was 34.4%, stable disease 40.6%, and progression 15.6%. Grade 3–4 toxicities were 7.8% hypertension, 4.7% anemia, 3.1% mucositis, 3.1% asthenia, 1.6% diarrhea, 1.6% anorexia, 1.6% worsening of renal function, and 3.1% cardiac events. Dose reduction to 0.89 mg was applied to 17.2% of patients, and the discontinuation rate due to toxicity was 5.8%. Median progression-free survival was 12.4 months, with 68.7% of patients alive at 12 months. The developing of hypertension predicted increased progression-free survival at multivariate analysis (HR, 0.128; 95% CI, 0.03–0.59; p = 0.008). Conclusions: Tivozanib showed good activity and favorable safety profile in a real-world cohort of unselected patients with mRCC. Predictive biomarkers of response to antiangiogenic therapy are urgently needed in order to identify RCC patients who could still receive a monotherapy with VEGFR inhibitors in the first line.

Prediction of early progression of metastatic renal cell carcinoma treated with first-line tyrosine kinase inhibitor.

Background:There are various alternative first-line therapeutic options besides tyrosine kinase inhibitors (TKIs) for metastatic renal cell carcinoma (mRCC). To inform therapeutic decision-making for such patients, this study aimed to identify predictive factors for resistance to TKI.Materials and methods:A total of 239 cases of mRCC patients who received first-line TKI therapy were retrospectively studied. Patients with a radiologic diagnosis of progressive disease within 3 months after initiating therapy were classified as primary refractory cases; the others were classified as non-primary refractory cases. The association between primary refractory cases and age, gender, pathology findings, serum c-reactive protein (CRP) level, metastatic organ status, and 6 parameters defined by the International Metastatic Renal Cell Carcinoma Database Consortium were analyzed.Results:Of 239 cases, 32 (13.3%) received a radiologic diagnosis of progressive disease within 3 months after initiating therapy. The rates of sarcomatoid differentiation, hypercalcemia, a serum CRP level of 0.3 mg/dL or higher, presence of liver metastasis, anemia, and time from diagnosis to treatment interval of less than a year were significantly higher in the primary refractory group. Multivariate analysis showed that sarcomatoid differentiation, hypercalcemia, a serum CRP level of 0.3 mg/dL or higher, and liver metastasis were independently associated with primary refractory disease. A risk-stratified model based upon the number of patients with these factors indicated rates of primary refractory disease of 4.0%, 10.1%, and 45.0% for patients with 0, 1, and 2 or more factors, respectively.Conclusions:Sarcomatoid differentiation, hypercalcemia, an elevated serum CRP level, and presence of liver metastasis were associated with primary refractory disease in mRCC patients receiving first-line TKI therapy. These results provide clinicians with useful information when selecting a first-line therapeutic option for mRCC patients.

MP14-16 EFFICACY OF NIVOLUMAB PLUS IPILIMUMAB IN PRIMARY TUMOR AS FIRST-LINE THERAPY IN THE PATIENTS WITH ADVANCED RENAL CELL CARCINOMA

You have accessJournal of UrologyKidney Cancer: Advanced (including Drug Therapy) I (MP14)1 Sep 2021MP14-16 EFFICACY OF NIVOLUMAB PLUS IPILIMUMAB IN PRIMARY TUMOR AS FIRST-LINE THERAPY IN THE PATIENTS WITH ADVANCED RENAL CELL CARCINOMA Hiroshi Kikuchi, Takahiro Osawa, Ryuji Matsumoto, Takashige Abe, Satoru Maruyama, Toru Harabayashi, Haruka Miyata, Akira Kashiwagi, Ataru Sazawa, Riyo Fukui, Ken Morita, Ichiro Takeuchi, Noboru Yamashita, Keita Minami, Tango Mochizuki, and Nobuo Shinohara Hiroshi KikuchiHiroshi Kikuchi More articles by this author , Takahiro OsawaTakahiro Osawa More articles by this author , Ryuji MatsumotoRyuji Matsumoto More articles by this author , Takashige AbeTakashige Abe More articles by this author , Satoru MaruyamaSatoru Maruyama More articles by this author , Toru HarabayashiToru Harabayashi More articles by this author , Haruka MiyataHaruka Miyata More articles by this author , Akira KashiwagiAkira Kashiwagi More articles by this author , Ataru SazawaAtaru Sazawa More articles by this author , Riyo FukuiRiyo Fukui More articles by this author , Ken MoritaKen Morita More articles by this author , Ichiro TakeuchiIchiro Takeuchi More articles by this author , Noboru YamashitaNoboru Yamashita More articles by this author , Keita MinamiKeita Minami More articles by this author , Tango MochizukiTango Mochizuki More articles by this author , and Nobuo ShinoharaNobuo Shinohara More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000001995.16AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: After the findings from CARMENA study, the role of cytoreductive nephrectomy (CN) should be considered in patient-tailored manner. Taking together with the new emergences of several effective combination therapies, the information of those effect on the primary site should be crucial for planning a future CN. This study aimed to focus exclusively on the size change of primary tumor following nivolumab plus ipilimumab (NivoIpi) treatment and elucidate the clinical factors associated with good response in primary tumor. METHODS: We retrospectively assessed 27 patients who were diagnosed with advanced renal cell carcinoma (RCC) and who had started NivoIpi. The changes in tumor size of the primary site were described using waterfall and spider plots. The parameters analyzed between responder and non-responder in the size of the primary tumor were International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk scores, peripheral blood markers and CRP. The ANOVA test was applied for the statistical analysis. RESULTS: The median age and follow-up periods were 66 years and 8.8 months, respectively. Nineteen patients were diagnosed with clear-cell renal cell carcinoma (ccRCC). Figure 1Ashow the maximum reduction from baseline in primary tumor and best overall response in ccRCC patients. Among ccRCC patients, 9 (47.4%) patients demonstrated significant response with 30% or more reduction from baseline within 4 months in primary tumors (Figure 1B). Of 6 patients who underwent nephrectomy, 3 patients whose primary tumors shrinked around 50-60% with reduction to 4 cm or less revealed no viable tumor cell in surgical specimens. Neutrophil-to-lymphocyte ratio and monocyte-to-lymphocyte ratio tended to decrease in those responders compare to non-responders among ccRCC patients (P=0.0944 and P=0.0691). Platelet-to-lymphocyte ratio significantly decreased in those responders (P=0.0391). CONCLUSIONS: In our experience, significant responses of primary tumor were obtained with NivoIpi in half cases of ccRCC. Of note, inflammation markers were possible predictive factor for treatment response of primary tumor. Although further study is needed, these observations help us to consider CN from the viewpoint of the radiological and pathological aspects. Source of Funding: None declared © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e259-e259 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Hiroshi Kikuchi More articles by this author Takahiro Osawa More articles by this author Ryuji Matsumoto More articles by this author Takashige Abe More articles by this author Satoru Maruyama More articles by this author Toru Harabayashi More articles by this author Haruka Miyata More articles by this author Akira Kashiwagi More articles by this author Ataru Sazawa More articles by this author Riyo Fukui More articles by this author Ken Morita More articles by this author Ichiro Takeuchi More articles by this author Noboru Yamashita More articles by this author Keita Minami More articles by this author Tango Mochizuki More articles by this author Nobuo Shinohara More articles by this author Expand All Advertisement Loading ...

THSD7A expression: a novel immunohistochemical determinant in predicting overall survival of metastatic renal cell carcinoma treated with targeted therapy.

The association of thrombospondin type 1 domain-containing 7A (THSD7A) expression, a novel angiogenesis-related marker, with survival outcomes of tumors including renal cell carcinoma (RCC) remains to be clarified. Therefore, we investigated the impact of THSD7A on outcomes of metastatic RCC (mRCC) patients treated with targeted therapy. A total of 86 mRCC patients were included. The expression of THSD7A in nephrectomy material of the patients was assessed by immunohistochemistry and expression patterns were categorized into two groups: negative (no staining) and positive. Univariable and multivariable Cox regression models evaluated the impact of THSD7A expression on progression free survival (PFS) and overall survival (OS) of the patients. THSD7A expression was determined in 77.9% of the patients. Kaplan-Meier analyses showed that while the patients with THSD7A expression had significantly inferior OS times than those with negative THSD7A expression (19.9months vs. 52.2months, P = 0.024, respectively), there was no association between THSD7A expression and PFS. The univariate analyses demonstrated that the significant variables in predicting OS were presence of bone metastasis (P = 0.030), THSD7A expression (P = 0.028), and International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) scoring system (P < 0.001). However, applying multivariate analyses, the independent variables in predicting OS were THSD7A expression (HR: 2.639, P = 0.037) and IMDC scoring system (P < 0.001). We revealed that THSD7A expression was associated with OS of mRCC patients treated with targeted therapy. There might be an important link between THSD7A expression and resistance to targeted therapy.

676P CABOPRE: A phase II study of cabozantinib (cabo) prior cytoreductive nephrectomy (CN) in metastatic renal cell carcinoma (mRCC)

Favorable response to systemic therapy has been suggested as a suitable approach to select ideal candidates for CN in mRCC. Cabo demonstrated clinical benefit as first-line therapy in mRCC patients with intermediate- or poor-risk International Metastatic Renal Cell Carcinoma Database Consortium criteria (IMDC). CABOPRE trial is a single arm prospective multicentre phase II trial to assess the efficacy and safety of neoadjuvant cabo in patients with clear cell mRCC and potential candidates to CN (EudraCT Number: 2018-001201-93).

Eosinophil counts as a relevant prognostic marker for response to nivolumab in the management of renal cell carcinoma: a retrospective study.

BackgroundDespite improvements in the management of renal cell carcinomas (RCC) with the advent of immunotherapy, only a few patients respond to these treatments. Predictors of response to nivolumab are currently being investigated but are still lacking.Aim of the studyTo evaluate eosinophil levels and their variations during treatment as an accurate biomarker for outcome in metastatic RCC treated with nivolumab.MethodsA retrospective analysis was carried out for patients with metastatic RCC treated with nivolumab. Absolute eosinophil counts, their variation, and relative change were evaluated at six weeks. Relative eosinophil change was categorized in three groups (≥10%‐decrease, no change, ≥10%‐increase). Univariable and multivariable analyses were performed to determine whether eosinophils and their variations were prognostic markers for response at the first scan evaluation, progression‐free survival, and overall survival.ResultsSixty‐five patients aged on average 66 years, 68% men, and 77% with good or intermediate International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk group were included. The median follow‐up was 16.6 months. Median overall survival (OS) was not reached for good prognosis and was 22.5 and 6.5 months for intermediate and poor prognosis, respectively. An increase in eosinophils and relative eosinophil change at six weeks of nivolumab was associated with a good response to immunotherapy (p = 0.012 and p = 0.024 respectively). In the group of patients with a 10%‐decrease in relative change, PFS reduced significantly compared to the other groups (p = 0.0044 with the 10%‐increase group and p = 0.03 with the no‐change group). This relative increase was independent of IMDC risks factors for better OS (HR = 3.3 [1.45–7.4]; p = 0.004). The eosinophil baseline level was not associated with response to treatment.ConclusionEosinophil levels and relative eosinophil change at 6 weeks might be good prognostic markers for response to nivolumab for metastatic RCC, and were associated with better PFS and OS.

Prognostic significance of hemoglobin-to-red cell distribution width ratio in patients with metastatic renal cancer.

The aim of the current research was toinvestigate the prognostic significance of pretreatment hemoglobin-to-red cell distribution widthratio (HRR) in patients with renal cell carcinoma (RCC). The neutrophil-to-lymphocyte ratio, systemic immune-inflammation index, lymphocyte-to-monocyte ratio (LMR) andHRR were analyzed retrospectively to assess their prognostic value usingKaplan-Meier curves and Cox regression analysis in 198 patients with RCC. High HRR (0.72) and high LMR (2.43) were found to be associated with longer progression-free survivaland overall survival. A multivariate analysis identified International Metastatic Renal Cell Carcinoma Database Consortiumprognostic score, tumor stage, node stage, LMRand HRR as independent prognostic factors for progression-free survival, as well as International Metastatic Renal Cell Carcinoma Database Consortium score, neutrophil-to-lymphocyte ratioand HRR for overall survival. HRR is a an independent prognostic parameter predicting the progression and survival of patients with RCC.

Prognostic factors for overall survival in patients with clear cell metastatic renal cell carcinoma: Model development and external validation with Memorial Sloan Kettering Cancer Center model and the international metastatic renal cell carcinoma database consortium model.

To develop a new prognostic model for the overall survival of patients with clear cell metastatic renal cell carcinoma (mRCC) using Korean Renal Cancer Study Group (KRoCS) database and compared it with 2 renowned prognostic models: the Memorial Sloan Kettering Cancer Center (MSKCC) and the international metastatic renal cell carcinoma database consortium (IMDC) models.Data of 790 patients diagnosed with mRCC and receiving targeted therapy as their first-line treatment were pooled to this study. Data from 4 hospitals (n = 619) were used to develop the new model and those from other 5 hospitals (n = 171) were used for external validation. After detecting prognostic factors in multivariable Cox proportional-hazards regression analysis, patients were classified into 3 risk groups, favorable (0), intermediate (1–2), and poor (3 and more) by the number of prognostic factors.Seven variables such as more than 2 metastasis sites, no prior nephrectomy, Eastern Cooperative Oncology Group performance status ≥2, low hemoglobin, high serum corrected calcium, high neutrophil, high serum alkaline phosphatase were identified as prognostic factors for poor overall survival. Also, risk groups were categorized into 3 groups; median overall survival was 61.1 months in favorable, 26.5 months in intermediate, and 6.8 months in poor group. KRoCS ranked the first in all 3 statistical parameters including akaike information criterion (AIC), concordance index and generalized R2 among other prognostic models.We developed the KRoCS model and validated it externally with demonstrating its superiority over MSKCC and IMDC models. The KRoCS model can provide useful information for counseling patients with clear cell mRCC regarding life-expectancy.

Cabozantinib in Pretreated Patients with Metastatic Renal Cell Carcinoma with Sarcomatoid Differentiation: A Real-World Study

Renal cell carcinoma with sarcomatoid differentiation is a highly aggressive form of kidney cancer. We aimed to analyze the outcomes of patients treated with cabozantinib for metastatic renal cell carcinoma with sarcomatoid features. We retrospectively collected data from 16 worldwide centers. Overall survival and progression-free survival were analyzed using Kaplan-Meier curves. Cox proportional models were used for univariate and multivariate analyses. We collected data from 66 patients with metastatic sarcomatoid renal cell carcinoma receiving cabozantinib as second-line (51%) or third-line (49%) therapy. The median progression-free survival from the start of cabozantinib was 7.59 months (95% confidence interval [CI] 5.75-17.49) and was longer in male patients (8.81 vs 5.95 months, p = 0.042) and in patients without bone metastases (7.59 vs 5.11 months, p = 0.010); the median overall survival was 9.11 months (95% CI 7.13-23.80). At the multivariate analysis, female sex (hazard ratio = 1.81; 95% CI 1.02-3.37,p = 0.046), bone metastases (hazard ratio = 2.62; 95% CI 1.34-5.10, p = 0.005), and International Metastatic Renal Cell Carcinoma Database Consortium criteria (hazard ratio = 3.04; 95% CI 1.54-5.99, p = 0.001) were significant predictors of worse overall survival. Our data show that cabozantinib is active in pretreated patients with sarcomatoid renal cell carcinoma. Biomarkers are needed in this field to select patients for multi-kinase inhibitors or other options.

CTLA4 promoter hypomethylation is a negative prognostic biomarker at initial diagnosis but predicts response and favorable outcome to anti-PD-1 based immunotherapy in clear cell renal cell carcinoma

BackgroundIn metastatic clear cell renal cell carcinoma (ccRCC), different combination therapies, each including anti-PD-1 immune checkpoint blockade (ICB), are applied as first-line treatment. Robust predictive biomarkers for rational upfront therapy...

Evolving biological associations of upfront cytoreductive nephrectomy in metastatic renal cell carcinoma.

Systemic responses to cytoreductive nephrectomy (CN) in the management of metastatic renal cell carcinoma (mRCC) are variable and difficult to anticipate. The authors aimed to determine the association of CN with modifiable International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk factors and oncological outcomes. Consecutive patients with mRCC referred for potential CN (2009-2019) were reviewed. The primary outcome was overall survival (OS); variables of interest included undergoing CN and the baseline number of modifiable IMDC risk factors (anemia, hypercalcemia, neutrophilia, thrombocytosis, and reduced performance status). For operative cases, the authors evaluated the effects of IMDC risk factor dynamics, measured 6 weeks and 6 months after CN, on OS and postoperative treatment disposition. Of 245 treatment-naive patients with mRCC referred for CN, 177 (72%) proceeded to surgery. The CN cases had fewer modifiable IMDC risk factors (P = .003), including none in 71 of 177 patients (40.1%); fewer metastases (P = .011); and higher proportions of clear cell histology (P = .012). In a multivariable analysis, surgical selection, number of IMDC risk factors, metastatic focality, and histology were associated with OS. Total risk factors changed for 53.8% and 57.2% of the patients from the preoperative period to 6 weeks and 6 months after CN, respectively. Adjusted for preoperative IMDC risk scores, an increase in IMDC risk factors at 6 weeks and 6 months was associated with adverse OS (hazard ratio [HR], 1.57; 95% confidence interval [CI], 1.13-2.19; P = .007; HR, 2.52; 95% CI, 1.74-3.65; P < .001). IMDC risk factors are dynamic clinical variables that can improve after upfront CN in select patients, and this suggests a systemic benefit of cytoreduction, which may confer clinically meaningful prognostic implications.

Prognostic significance of the controlling nutritional status score in patients with metastatic renal cell carcinoma diagnosed before an era of first-line immune-oncology combination therapies.

To explore the prognostic role of the controlling nutritional status score in patients with metastatic renal cell carcinoma. We retrospectively analyzed 107 patients with metastatic renal cell carcinoma who received their diagnosis between 2007 and 2018 and were treated with or without a first-line interferon or tyrosine kinase inhibitor at a single cancer center. The controlling nutritional status score was based on values for albumin, lymphocyte count and total cholesterol at the metastatic renal cell carcinoma diagnosis. Association of the controlling nutritional status score and clinical variables, including the Memorial Sloan-Kettering Cancer Center and the International Metastatic Renal Cell Carcinoma Database Consortium risk classifications, with overall survival was examined using the Cox proportional hazard model. Predictive accuracy of the prognostic factors was assessed using Harrell's concordance index. First-line interferon and tyrosine kinase inhibitor were given to 48 (45%) and 41 (38%) patients, respectively, and 28 (26%) and 33 (31%) patients underwent cytoreductive nephrectomy and metastasectomy, respectively. During follow-up (median: 36.3months), 64 patients died. The median controlling nutritional status score was 2 (range: 0-8). A controlling nutritional status score≥2 was significantly associated with shorter overall survival (P<0.01) independently of the Memorial Sloan-Kettering Cancer Center and International Metastatic Renal Cell Carcinoma Database Consortium risk classifications. Integration of the controlling nutritional status score into the Memorial Sloan-Kettering Cancer Center and International Metastatic Renal Cell Carcinoma Database Consortium risk classifications improved concordance index from 0.702 to 0.770 and from 0.698 to 0.749, respectively. The controlling nutritional status score may serve as a prognostic biomarker objectively reflecting the general physical condition of patients with metastatic renal cell carcinoma treated with or without first-line interferon or tyrosine kinase inhibitor in terms of nutritional and immuno-inflammatory status.