Heng Risk Groups Research Articles

Metastatic renal cell carcinoma to the pancreas: Clinical features and treatment outcome.

Metastatic renal cell carcinoma to the pancreas (PM-RCC) is infrequent; we sought to describe the characteristics of PM-RCC and analyze the outcomefollowing treatment. Data of 3107 mRCC patients treated between 1992 and 2007 from the Korean Renal Cancer Study Group database were obtained to identify 300 (9.7%) PM-RCC patients. Characteristics and survival were analyzed and compared to the rest of the mRCC, according to the timing of metastasis and surgical treatments received. PM-RCC was younger at initial diagnosis (55.0 vs. 58.2 years), more frequently in women (30.3% vs. 22.3%), and metachronous (65.3% vs. 41.9%) with a longer disease-free period (82.0 vs. 33.0 months). Overall survival (OS) was significantly better in PM-RCC but pancreas metastasectomy was associated with improved OS only among metachronous PM-RCC. In the 132 metachronous PM-RCC with pancreas metastasectomy, median recurrence-free survival was 17.2 months and we found Heng risk group (hazard ratio [HR] = 2.384, 95% confidence interval [CI] = 1.213-4.684), younger age (HR = 0.965, 95% CI = 0.945-0.987), shorter interval to pancreas metastasis (HR = 0.993, 95% CI = 0.986-0.999), and Eastern Cooperative Oncology Group performance status to be predictive of early progression following pancreas metastasectomy. Compared to the other mRCC, PM-RCC demonstrated a favorable prognosis. Pancreas metastasectomy was associated with prolonged survival in the metachronous PM-RCC with a long progression-free period.

A Retrospective Analysis of the Impact of Metastasectomy on Prognostic Survival According to Metastatic Organs in Patients With Metastatic Renal Cell Carcinoma.

This study evaluated the effects of metastasectomy on overall survival (OS) and progression-free survival (PFS) in metastatic renal cell carcinoma (mRCC) according to metastatic organs. The medical records (2005–2017) of 273 patients with mRCC were analyzed retrospectively to evaluate OS and PFS according to metastatic organs and their metastasectomy states. The Cox proportional hazard model was used to determine the prognostic significance of metastasectomy. The Kaplan-Meier curve and log-rank test were used to compare groups with different modalities and metastatic organs at a statistical significance of p < 0.05. The overall median age was 57 years; 175 (64.3%) and 83 (30.4%) patients received cytoreductive nephrectomy and metastasectomy, respectively. The metastasectomy group was significantly younger and had a lower clinical T stage with significantly better PFS/OS (20.2/32.0 vs. 9.7/12.8 months) than that in the non-metastasectomy group (N = 190, p < 0.05). Liver with lung metastases were the worst metastatic combination for survivals in which liver metastasis was the only significant unfavorable risk factor for both PFS (HR 1.67) and OS (HR 1.74) (p < 0.05). Multivariable analysis confirmed that metastasectomy was a significant favorable risk factor for PFS (HR 0.70) and OS (HR 0.56) (p < 0.05) along with non-clear cell type (HR 0.61 for PFS), whereas the nuclear grade and poor Heng risk group were unfavorable risk factors (HR > 2.0) for both PFS and OS (p < 0.05). Metastasectomy and the affected metastatic organs significantly influenced prognostic survival in mRCC.

A retrospective comparative study of progression-free survival and overall survival between metachronous and synchronous metastatic renal cell carcinoma in intermediate- or poor-risk patients treated with VEGF-targeted therapy.

IntroductionThe aim of this study was to compare progression-free survival (PFS) and overall survival (OS) between metachronous and synchronous metastatic renal cell carcinomas treated with VEGF-targeted therapy.MethodsBetween 2005 and 2014, 93 (78.8%) intermediate- and 25 (21.2%) poor-Heng-risk patients, including 32 (27.1%) patients with metachronous and 86 (72.9%) patients with synchronous renal cell carcinoma, were enrolled retrospectively. PFS and OS values were compared according to the number of risk factors and treatment-free interval using the Kaplan-Meier method and log-rank test. The prognostic risk factors were also evaluated using a Cox proportional hazard model, with a p-value < 0.05 indicating statistical significance.ResultsDuring a median 5.0-month treatment and 59.3-month follow-up, analysis of the PFS/OS of SM (5.2/9.6 months) and MM (9.6/20.1 months) yielded a significant difference in OS (p = 0.010). However, there was no significant difference when Heng risk groups and treatment-free interval were considered (p > 0.05). There was a significant difference in PFS (hazard ratio: 1.81) and OS (hazard ratio: 2.19) with increasing number of Heng risk factors among patients with synchronous renal cell carcinoma and a treatment-free interval <1 year. Metastatic type, anemia, and neutrophilia were significant predictive factors for OS in multivariable analysis (p < 0.05).ConclusionThe metastatic type of renal cell carcinoma (synchronous or metachronous) significantly affects survival; metachronous type is associated with more favorable outcomes than synchronous type. However, after stratification according to Heng risk factors and treatment-free interval, the differences in survival between metachronous and synchronous type were insignificant.

Trends in exposure to multiple lines of treatment and survival of patients with metastatic renal cell carcinoma: A real-world analysis.

e16064 Background: In recent years, several new agents have been introduced into clinical practice for patients (pts) with metastatic renal cell carcinoma (mRCC). The aim of this study was to describe the difference in terms of exposure to multiple lines of treatment and overall survival (OS) between two groups of pts who started therapy for mRCC in two different periods of time (period 1: 2005-2010 and period 2: 2011-2016). Methods: Data were retrospectively collected from the database of the Istituto Nazionale Tumori of Milan. The proportion of pts who received subsequent lines of treatment after first disease progression (PD) was compared between the two groups of pts. OS was defined as time from the start of first-line treatment to death or last follow-up. Unadjusted and adjusted analyses for Heng risk groups were done. Results: Overall,457 pts with mRCC were evaluated: 274 pts (60%) started treatment in period 1 and 183 (40%) in period 2. Most pts in both groups had intermediate risk (65.7% and 86.3% respectively). The proportion of poor-risk pts was significantly higher in period 1 (21.2% vs 7.7%). Among pts who stopped first-line treatment due to PD, pts in period 2 had a higher chance of receiving second-line treatment as compared to pts of period 1 (80.8% vs 64.7%, 95% CI 1.31-4.04, p = 0.003). Similarly, among those who stopped second-line treatment due to PD, pts in period 2 had a higher chance of receiving a third-line treatment compared to pts in period 1 (71.2% vs 49.3%, 95% CI 1.32-4.87, p = 0.004). In the whole study population, median OS (mOS) was 24.9 months (95% CI 21.6-31.1): 21.7 months (95% CI 18.8-26.3) in pts of period 1 and 38.2 months (95% CI 27.7-49.0) in pts of period 2 (Hazard Ratio [HR] 0.65,95% CI 0.49-0.84, p = 0.001) respectively. When adjusted for Heng groups, OS remained significantly longer for pts of period 2 (HR 0.76, 95% CI 0.57-1.00, p = 0.05). Conclusions: mRCC pts who started a treatment over the last 5 years have been exposed to a higher number of treatment lines as compared to those treated before 2011. Our data suggest that the increase of treatment options as well as a better clinicians’ expertise is associated with a better outcome.

C27 - A retrospective multicenter characterization of patients with metastatic renal cell carcinoma: the Sicilian “real-world” experience

Background: Over the past 10 years the target of mTOR and VEGF signaling pathways with new oral agents has revolutionized the treatment of metastatic renal cell carcinoma (mRCC) with a clinically significant improvements in median overall survival. In this retrospective study we analyzed the pathological and clinical features, Heng prognostic group, number and sites of metastasis, targeted therapy sequence, treatment-related toxicity and dose reductions, therapeutic responses on CT imaging and the outcome of a Sicilian mRCC patient series treated with new targeted agents. Material and methods: 122 patients (P) with mRCC diagnosis between January 2012 and April 2016 were collected from 11 Sicilian cancer centers. The objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) were assessed using Response Evaluation Criteria in Solid Tumor ver. 1.1 criteria and the Kaplan-Meier method with log-rank test. Results: Study population evaluable is composed by 118 P (36 women; 82 man). Histology: clear cell RCC 90 P (76%), other 28 P (24%). Concomitant relevant diseases at diagnosis: hypertension 59 P (50%), Type II diabetes 21 P (18%). Disease stage at diagnosis: stage I 16 P (14%), stage II 21 P (18%), stage III 13 P (11%), stage IV 54 P (46%). Heng risk group in metastatic P at diagnosis: Favorable 4 P (7%), Intermediate 46 P (86%), Poor 4 (7%). I line treatment was completed in 80 P: Pazopanib 29 P (36%), Sunitinib 49 P (61%) and Sorafenib in 2 P (3%). II line treatment was administred in 37 P: Axitinib 4 P (11%), Everolimus 28 P (76%), Sunitinib 3P (8%), Sorafenib 2 P (5%). III line treatment was administered in 8 P: Everolimus 3 P(38%), Sorafenib 3 P(38%), Sunitinib 2 P(24%). Conclusions: Hypertension is confirmed an established risk factor for RCC. The proportion of metastatic disease at diagnosis is almost 50% and intermediate risk is the most frequent risk group. Basing on current data the most used sequence of targeted agents in Sicily for the treatment of mRCC is Sunitinib-Everolimus. Further clinical data, the correlation between PFS and treatment administered, number and sites of metastasis, are under investigation.

Macrocytosis during sunitinib treatment predicts progression-free survival in patients with metastatic renal cell carcinoma.

Sunitinib, a multi-targeted receptor tyrosine kinase inhibitor, is a first-line treatment for metastatic renal cell carcinoma (mRCC) in patients in ‘low’ and ‘intermediate’ Memorial Sloan Kettering Cancer Center and Heng risk groups. Disruptions of hematopoiesis, such as anemia, neutropenia, and thrombocytopenia, are typically observed during sunitinib treatment. When it comes to RBC parameters, an increase in mean cell volume (MCV) tends to occur, meeting the criteria for macrocytosis in some patients (MCV > 100 fL). We examined changes in RBC parameters of 27 mRCC patients treated with sunitinib (initial dose of 50 mg/day, 6-week treatment: 4 weeks on, 2 weeks off) and correlated them with progression-free survival time (PFS). Patients who had macrocytosis after 3 treatment cycles had significantly longer PFS than those whose MCV stayed less than 100 fL (not reached vs. 11.2 months, p < 0.001). We also found a correlation between MCV values after the first and third treatment cycles and the risk of progression: HR of 0.9 (0.81–0.99) and 0.76 (0.65–0.90) per 1 fL increase in MCV, respectively. The mechanism of MCV elevation during sunitinib treatment has not yet been fully explained. One of the probable causes is sunitinib’s inhibitory influence on c-Kit kinase, as is the case with imatinib. For mRCC patients, this phenomenon could help predict PFS, but since our sample was small, further studies are essential.

Prognostic Value of SETD2 Expression in Patients with Metastatic Renal Cell Carcinoma Treated with Tyrosine Kinase Inhibitors

Mutations of SETD2 occur in 3% to 16% of clear cell renal cell carcinoma cases. Previous studies identified an association between SETD2 mutation and prognosis of patients with nonmetastatic clear cell renal cell carcinoma. In this study we explored the prognostic and predictive value of SETD2 expression in patients with metastatic renal cell carcinoma treated with targeted therapy. We retrospectively enrolled 138 patients with metastatic renal cell carcinoma treated with sunitinib or sorafenib at a single institution from 2007 to 2014. SETD2 expression was assessed by immunohistochemistry on tissue microarrays. After excluding those patients with loss of followup or unavailable tissue samples, 111 were included in the study. Low SETD2 expression was associated with reduced overall survival (p <0.001) and progression-free survival (p=0.001). After adjustment for histological type, Heng risk group and drugs used for targeted therapy, SETD2 was defined as an independent prognostic marker for overall survival (HR 2.535 [95% CI 1.429-4.497], p=0.001) and progression-free survival (HR 1.755 [95% CI 1.031-2.988], p=0.038). Its prognostic value for overall survival was more predominant in patients with clear cell renal cell carcinoma (p <0.001) or patients in the intermediate risk group of Heng risk criteria (p <0.001), while its predictive value for progression-free survival was more predominant in patients treated with sorafenib (p<0.001). SETD2 could also be combined with the Heng risk model for better overall survival prediction. SETD2 is a potential prognostic biomarker for overall survival and progression-free survival prediction in patients with metastatic renal cell carcinoma receiving targeted therapy. However, it remains to be seen whether this is generalizable to other ethnicities and prospective external validation is required.

CheckMate 025 phase III trial: Outcomes by key baseline factors and prior therapy for nivolumab (NIVO) versus everolimus (EVE) in advanced renal cell carcinoma (RCC).

498 Background: Based on assessment by an independent Data Monitoring Committee, a phase III trial of NIVO (n=410) vs EVE (n=411) in previously treated patients with advanced or metastatic RCC (NCT01668784) was halted early as it met its endpoint; superior overall survival (OS) was seen with NIVO vs EVE. We present outcomes by key baseline factors, prior therapy, and subsequent anticancer therapy. Methods: Patients with 1 or 2 prior anti-angiogenic therapies and measurable disease (RECIST v1.1) were randomized 1:1 to NIVO 3 mg/kg IV every 2 weeks or EVE 10 mg orally once daily. Primary endpoint was OS. A key secondary endpoint was objective response rate (ORR). Results: The Table shows OS and ORR by key baseline factors. Median follow-up was 17-18 mo. 77% and 23% of patients received 1 or 2 prior anti-angiogenic therapies, respectively, for advanced RCC, mainly sunitinib (63%) or pazopanib (32%). In patients who had prior sunitinib, median OS was 23.6 mo for NIVO vs 19.8 mo for EVE; in those who had prior pazopanib, median OS was not estimable (NE) for NIVO vs 17.6 mo for EVE. For those who had prior IL-2 (10%), median OS was NE for NIVO vs 17.2 mo for EVE. Outcomes by subsequent anticancer therapy are planned. Conclusions: A consistent OS benefit with NIVO vs EVE was found across baseline factors (Karnofsky performance status [KPS], Heng risk group, number of prior therapies), and specific prior therapies (sunitinib, pazopanib, IL-2) in previously treated patients with advanced RCC. ORR benefit with NIVO was also seen across baseline factors. Clinical trial information: NCT01668784. [Table: see text]

Prognostic tissue biomarker exploration for patients with metastatic renal cell carcinoma receiving vascular endothelial growth factor receptor tyrosine kinase inhibitors.

In metastatic renal cell carcinoma (mRCC), the prognostic role of several tumor tissue biomarkers has been evaluated, but the results were controversial. This study aims to verify the prognostic importance of selected tumor tissue biomarkers in patients with mRCC. The clinicopathological features, immunohistochemical staining and scoring for select tissue biomarkers, treatment, and outcome of patients with mRCC treated with vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKIs) between July 2006 and March 2011 at Asan Medical Center in Seoul, South Korea, were reviewed. In total, 123 patients met the inclusion criteria. Most patients had clear-cell carcinoma (107 patients, 87.0%). First-line VEGFR TKIs were sunitinib (97 patients, 78.9%), sorafenib (23 patients, 18.7%), and pazopanib (3 patients, 2.4%). With a median follow-up period of 60.0months (95% confidence interval (CI), 56.3-63.6), median overall survival (OS) and progression-free survival (PFS) were 25.6months (95% CI, 19.2-32.0) and 12.2months (95% CI, 8.1-16.3), respectively. In the multivariable analysis for OS, carbonic anhydrase IX (CAIX; 47.5% or less vs. more than 47.5%, p = 0.014), sarcomatoid change (40% or less vs. more than 40%, p < 0.001), tumor necrosis (20% or less vs. more than 20%, p = 0.006), and Heng's risk group (good vs. intermediate vs. poor, p = 0.011) were identified as independent prognostic factors. In the multivariable analysis for PFS, CAIX (p < 0.001), phosphatase and tensin homolog (PTEN; 45% or less vs. more than 45%, p = 0.004), sarcomatoid change (p = 0.002), and tumor necrosis (p = 0.001) were identified as independent factors affecting PFS. CAIX and PTEN had prognostic importance for mRCC patients receiving first-line VEGFR TKI. Future validation and mechanistic studies are required.

Prognostic biomarker exploration for patients with metastatic renal cell carcinoma receiving VEGFR TKI.

491 Background: To verify the prognostic importance of selected tumor tissue biomarkers in metastatic renal cell carcinoma (mRCC) patients (pts), we performed immunohistochemical (IHC) staining in tumor sample and statistical analyses. Methods: The clinicopathological features, treatment, and outcome of mRCC pts treated with vascular endothelial growth factor tyrosine kinase inhibitor (VEGFR TKI) between July 2006 and March 2011 at our center were reviewed. IHC staining for FGF base, FGFR1, 2, 3, and 4, HGF, PTEN, CAIX, pS6, HIF-1a, HIF-2a, IL-8, mTOR was done, and each specimen was scored based on the staining intensity and the percentage of positive cells. We performed univariate and multivariable analyses to verify prognostic factors for overall survival (OS). Results: We found 123 pts who met inclusion criteria. Most pts had clear cell carcinoma (107 pts, 87.0%). Fuhrman’s nuclear grade (NG) was 2 in 21 (17.1%), 3 in 49 (39.8%), and 4 in 52 (42.3%), respectively. Sarcomatoid change and coagulative necrosis were found in 51 pts and 58 pts. Using Heng’s criteria, 20 pts (16.3%), 87 (70.7%), and 16 (13.0%) belonged to favorable, intermediate, and poor risk group, respectively. First-line VEGFR TKIs prescribed were sunitinib (97 pts, 78.9%), sorafenib (23 pts, 18.7%), and pazopanib (3 pts, 2.4%). In univariate analysis, CAIX (less than 47.5% vs 47.5% or more, p=0.001), mTOR (20% or less vs more than 20%, p=0.0032), Heng risk group (good vs intermediate vs poor, p&lt;0.001), sarcomatoid change (40% or less vs more than 40%, p&lt;0.001), coagulative necrosis (20% or less vs more than 20%, p&lt;0.001), Furhman NG (2 vs 3 vs 4, p=0.037) were statistically significant. In multivariable analysis, CAIX, Heng risk group, sarcomatoid change, and hyaline necrosis were identified as independent prognostic factors (Table). Conclusions: All investigated biomarkers but CAIX did not show prognostic importance for mRCC pts receiving VEGFR TKI. [Table: see text]

Survival Outcomes and Tumor IMP3 Expression in Patients with Sarcomatoid Metastatic Renal Cell Carcinoma.

Metastatic renal cell carcinoma with sarcomatoid histology (SmRCC) is associated with poor survival. No data is available from randomized trials on the efficacy of vascular endothelial growth factor (VEGF) and mammalian target of rapamycin (mTOR) inhibitors in SmRCC. We identified SmRCC patients from a single institutional database. To identify predictive and prognostic biomarkers, immunohistochemistry (IHC) analysis was performed on the tumor samples for downstream targets of VEGF and mTOR pathways. Survival outcomes were stratified by IHC analysis, extent of sarcomatoid component, Memorial Sloan-Kettering Cancer Center (MSKCC), and Heng risk criteria. Twenty-seven patients with SmRCC were included. First line therapy included targeted therapy (n = 19), immunotherapy (n = 4), cytotoxic chemotherapy (n = 1), and no treatment (n = 3). Median OS was 8.2 months (95% CI 3.8–14.2 months). Median survival in months, based on MSKCC and Heng risk groups, was favorable 89.3 versus 84.5, intermediate 9.5 versus 12.7, and poor 3.9 versus 5.1. None of the IHC markers predicted outcomes of treatment with VEGF or mTOR inhibitors. Only tumor IMP3 expression was associated with inferior OS, although not statistically significant (IMP3 negative 14.2 versus IMP3 positive 4.9 months; HR 0.46, 95% CI 0.16–1.21; P = 0.12). The study was limited by small sample size.

826P - Contribution of Tumor Burden and Body Composition Parameters As Prognostic Factors of Metastatic Renal Cell Carcinoma (Mrcc) Treated By Targeted Therapy

ABSTRACT Aim: We previously showed that tumor burden (TB) and skeletal muscle density (SMD) at baseline are independent prognostic factors for overall survival (OS) in mRCC. We aimed to analyze the respective roles of baseline TB and Heng score, baseline and 12 week- body mass index (BMI) (weight /height2) and body composition (BC) on OS in mRCC included in trials evaluating targeted therapy. Methods: Baseline and 12 weeks- TB, BMI, adipose tissue (AT), muscular muscle (MM) and SMD were assessed using previously reported techniques. To withdraw causes of early death, OS was estimated from 12 weeks after therapy initiation, using Kaplan-Meier method and compared across strata using log-rank test. To identify prognostic factors, impact of baseline and 12 week- body components were assessed in a multivariable Cox proportional hazards models adjusted for Heng risk groups. Results: 116 pts, treated with sorafenib (n = 35), sunitinib (n = 33) or everolimus (n = 18) or placebo (n = 30) with full data for TB, BMI and BC, have been analyzed. BMI was low ( 25 kg2/m2) in 3 (3%), 47 (41%) and 66 (56%) pts respectively. Median OS was 18 months, 95% Confidence Interval (CI) = [16;21]. Median estimates and hazard ratios derivated from the multivariable Cox model were: Median OS (weeks) Hazard Ratio (95%CI) p-value Heng risk High 6 1 - 0.0002 Intermediate 45 0.2 0.1 – 0.6 Favorable 112 0.1 0.0 – 0.3 TB >= 19 cm 76 1 - 0.0002 9.5-19 cm 85 1.2 0.7 – 2.1 161 0.4 0.2 – 0.7 BMI Normal 112 1 - 0.007 Low 154 0.8 0.2-3.2 High 66 1.9 1.2 – 3.1 SMD and BC were not independently associated with OS. Conclusions: High/intermediate risk Heng score, large TB and high BMI are independent predictors of shorter survival in pts alive after 12 weeks of treatment. Mechanisms underlying the surprising deleterious effect of high BMI could not be determined from body composition impact analysis. After adjustment on TB, high muscle density is not protective any more. Disclosure: Y. Loriot: Advisory board Bayer; B. Escudier: Advisory board Bayer, Pfizer, Novartis Honoraria from Bayer, Roche, Pfizer, Genentech, Novartis, AVEO, GSK. All other authors have declared no conflicts of interest.

819P - Hypertension, Neutropenia, Thrombocytopenia, Normal Sodium and Ldh Within the First 12 Weeks of Treatment As Independent Biomarkers of Outcome in Metastatic Renal Cell Carcinoma (Mrcc)

ABSTRACT Aim: Treatment-related hypertension and neutropenia are biomarkers of outcome in patients with mRCC. Other biomarkers are needed. Methods: Baseline Heng risk group status and time-dependent biomarkers within the first 12 weeks after treatment initiation were analyzed with univariate and multivariate Cox proportional hazard model in a complete national cohort of all Danish mRCC patients receiving first line tyrosinekinase-inhibitors (TKI) or interleukin-2 based immunotherapy (IT) from 2006 – 2010. Measurements were made day 1 of each cycle after the first cycle. Results: 735 patients received first line TKI (59%) or IT (41%). Overall median survival (OS) was 14.0 months and median OS for baseline Heng favourable, intermediate and poor risk groups were 33.4, 18.5 and 5.8 months, respectively (p LLN and LDH OS per biomarker profile within 12 weeks treatment for baseline Heng risk group status Favourable Intermediate Poor Biomarker profile N OS 95% CI p value N OS 95% CI p value N OS 95% CI p value Good 40 38.9 29.7-NA 0.112 175 25.7 20.9-33.6 67 12.8 10.7-19.8 Poor 17 28.7 23.4-NA 77 12.0 7.9-16.5 86 6.4 5.2-10.8 This table contains 462 patients with complete data; OS = Overall Survival (months); N = Number; CI = Confidence interval; NA = Not applicable. Conclusions: Hypertension, neutropenia, thrombocytopenia, normal sodium, and LDH within the first 12 weeks of treatment are independent biomarkers of favourable outcome in mRCC and provide additional prognostic information for patients in Heng intermediate and poor risk groups. These biomarkers seem independent of treatment type. Disclosure: A.V. Soerensen: has received research funding from Pfizer; R. Sandin: is a fulltime employee at Pfizer and has stock ownership; F. Donskov: has received a research grant from Novartis and GSK. All other authors have declared no conflicts of interest.

824P - Differences Between Patients (Pts) with Metastatic Renal Cell Carcinoma (Mrcc) Who Develop Brain Metastases (Bm) Versus Those Who Do Not

ABSTRACT Aim: Brain imaging is not performed as routine follow-up in mRCC, and BM are commonly discovered mainly in pts reporting symptoms. The identification of differences between pts who develop BM vs those who do not, may allow us to define a subgroup more at risk. Methods: mRCC pts enrolled in clinical trials from 01/05 to 11/13 at Gustave Roussy with brain scan evaluation without neurological symptoms or for the onset of symptoms were evaluated. We compared the clinical and pathological characteristics, including location and number of metastatic sites in pts who develop BM during the course of the disease (BM+) and those who did not (BM-). Results: 234 pts were included with a median follow-up of 11 years (95%CI;10-12). Median age was 56 years, 74% pts were male, 89% with clear-cell histology, 9% with sarcomatoid features, 67% with intermediate Heng risk group. N = 44 pts developed BM either at diagnosis of mRCC (n = 8) or during the follow-up. There was no difference in prognostic groups between BM+ and BM-. The median number of metastatic sites at the time of first line treatment was 3 vs 2 (p Conclusions: Classical prognostic factors as well as efficacy of first-line therapy do not seem to be different in pts who will develop BM. In this preliminary analysis, pts with lung and/or adrenal gland metastases have a higher risk of developing BM. In addition, the number of metastatic sites is higher in BM+ pts. Although this finding may have several biases, it warrants to be validated in larger and different cohorts of mRCC pts. Disclosure: B. Escudier: Honoraire: Novartis, Pfizer, GSK, Bayer. All other authors have declared no conflicts of interest.

Comparative Efficacy of Sunitinib versus Sorafenib as First-Line Treatment for Patients with Metastatic Renal Cell Carcinoma

Background: This study investigated the efficacy and toxicity of sorafenib and sunitinib as primary treatment for patients with metastatic renal cell carcinoma (mRCC). Methods: We identified 49 and 220 patients treated with sorafenib and sunitinib, respectively, as first-line therapy in the Asan Medical Centre from April 2005 to March 2011. Results: Disease control rates of 71 and 74% were achieved with sorafenib and sunitinib, respectively (p = 0.687). After a median follow-up of 27.6 months, progression-free survival (PFS) and overall survival (OS) were not significantly different between the sorafenib and the sunitinib group (PFS 8.6 vs. 9.9 months, respectively, p = 0.948, and OS 25.7 vs. 22.6 months, p = 0.774). Patients treated with sorafenib required dose reduction due to toxicities less frequently than those treated with sunitinib (37 vs. 54%, p = 0.034). Haematological toxicity of grade 3 or 4 was more common in the sunitinib group than in the sorafenib group (45 vs. 4%, p < 0.001). Multivariate analysis showed old age, Heng's risk group, and bone and liver metastases, but not the type of vascular endothelial growth factor tyrosine kinase inhibitor, were independent prognostic factors affecting OS. Conclusion: The results of this study indicate that sorafenib has comparable efficacy to sunitinib in the treatment of mRCC patients and fewer and less severe toxicities, but the number of patients included in the study was small.

Conditional survival in patients treated with vascular endothelial growth factor-targeted therapy for advanced renal cell carcinoma

Conditional survival (CS) offers more relevant prognostic information for patients once they have survived for some time. The objective of this study was to determine the CS for advanced renal cell carcinoma (RCC) patients treated with vascular endothelial growth factor-targeted therapy. A total of 345 patients treated between 2006 and 2011 fulfilled the inclusion criteria and were reviewed for analyses. The 1-year conditional and actual survival rates were calculated for survivors from treatment to month 24. Subgroup-specific CS rates were generated after adjustment of the covariate influence. The Cox proportional hazard models were used to assess the prognostic factors at baseline and 1-year landmark. The probabilities of surviving an additional year given survival to 6, 12, 18, and 24 months were 72.2, 76.3, 78.2, and 78.6 %, respectively. Remarkable increase in CS was observed in patients initially classified as intermediate or poor risk according to Heng risk groups. For patients survived 24 months after treatment, the adjusted CS for the following year was over 80 % regardless of initial risk attribution. Compared to baseline analysis, Heng risk groups were less predictive of survivorship after surviving 1 year. The addition of disease control status to multifactorial model significantly improved survival estimation for 1-year survivors (p < 0.01). CS provides useful information regarding life expectancy for survivors of advanced RCC treated with targeted therapy. Furthermore, disease control status within a specific period of time is critical to the prediction of subsequent survival.

Conditional survival (CS) for patients with metastatic renal cell carcinoma (mRCC) treated with vascular endothelial growth factor (VEGF)-targeted therapy (TT): Results from the International mRCC Database Consortium.

358 Background: Survival estimates for patients with mRCC are traditionally reported from the time of TT initiation. These survival projections, however, may not be applicable to patients who have already survived a period of time after initiating therapy. CS accounts for elapsed time since starting therapy, providing more relevant prognostic information. Methods: Data on 1673 patients treated with first-line VEGF TT between 4/7/2003 and 10/12/2010 was analyzed. Median follow up for patients still alive is 20.1 months. Conditioned survival was calculated on the set of patients alive or on TT at 3 months and using 3 months increments for up to 18 months. Results: The 2-year CS probability tends to slightly improve from 44 to 51% when conditioned on having already survived 0 to18 months since initiation of TT, respectively. The Heng et al (JCO 2009) risk criteria (defined at therapy initiation) retains prognostic ability over time independent of previous survival time or previous time on TT up to 18 months (p&lt;0.0001 for all comparisons). In the subgroup analysis stratified by Heng risk groups, 2-year CS minimally changes over time in the favorable (FAV) and in the intermediate (INT) groups, but in the poor risk group, the 2-year CS improves from 11% initially to 33% after 18 months. When conditioned on time on TT, 2-year CS improves from 44% to 68% overall, from 74% to 90% in the FAV risk group, 49% to 57% in the INT risk group and 11% to 73% in the poor-risk group. Conclusions: Conditional survival may be a more relevant measure of prognosis for those who have already survived or have been on TT for a period of time. The largest improvement was seen in patients in the poor risk group. [Table: see text]

Cessation of vascular endothelial growth factor–targeted therapy in patients with metastatic renal cell carcinoma

The current treatment of metastatic renal cell carcinoma (mRCC) with vascular endothelial growth factor (VEGF)-targeted agents is continuous therapy until progression of disease (PD) or unacceptable toxicity. Chronic mild to moderate toxicity and risk of long-term toxicity ensue for some patients. It is hypothesized that patients with an initial response to treatment can maintain disease control off all therapy for a period of time. A retrospective study of patients with mRCC who initiated VEGF-targeted therapy between January 2004 and December 2009 at The Cleveland Clinic Foundation, Cleveland, Ohio, or Institut Gustave-Roussy, Villejuif, France, was conducted. Patients had achieved RECIST (Response Evaluation Criteria in Solid Tumors)-defined stable disease or better on therapy, and were then taken off all therapy for reasons not including disease progression. Patient, disease, and therapy characteristics were recorded. The primary objective was progression-free survival (PFS), measured as the time from discontinuation of therapy to RECIST-defined PD. Forty patients were identified. After a median follow-up of 29.7 months (range, 4.2 to 84.7 months), 25 patients (63%) had PD off therapy (median PFS, 10.0 months; range, 1.4-27.2 months). Among these patients, 8 (32%) had progression in sites that were not previously involved with disease. Heng risk group (hazard ratio, 2.49; 95% confidence interval, 1.19-5.22; P = .011) and achievement of a complete response prior to discontinuing therapy (hazard ratio, 0.20; 95% confidence interval, 0.04-0.86; P = .025) were independent predictors of PFS in a multivariable Cox proportional hazards model. A select subset of mRCC patients achieving stable disease or better on VEGF-targeted therapy can be observed off all therapy. Further prospective investigation is warranted.