Risk Metastatic Renal Cell Carcinoma Research Articles

Strategic treatment pause of first-line immune checkpoint inhibitor + VEGFR-tyrosine kinase inhibitor in patients with good or intermediate risk metastatic renal cell carcinoma (mRCC) in response at 1 year of treatment (SPICI-GETUG R05): A non-inferiority randomized clinical trial.

Strategic treatment pause of first-line immune checkpoint inhibitor + VEGFR-tyrosine kinase inhibitor in patients with good or intermediate risk metastatic renal cell carcinoma (mRCC) in response at 1 year of treatment (SPICI-GETUG R05): A non-inferiority randomized clinical trial.

Efficacy of Sunitinib in Patients With Favorable and Intermediate Risk Metastatic Renal Cell Carcinoma - Lithuanian National Cancer Institute Experience.

According to the European Society for Medical Oncology (ESMO) and National Comprehensive Cancer Network (NCCN) recommendations, sunitinib is one of the recommended regimens for favorable and intermediate-risk metastatic renal cell carcinoma (mRCC) patients. The objective of this study was to evaluate sunitinib efficacy as a first-line treatment for mRCC patients with favorable/intermediate prognostic risk in a real-world setting. Patients diagnosed with mRCC and confirmed as appropriate candidates for the first-line systemic treatment were included in this retrospective study. The prognostic risk was evaluated according to the model of the International Metastatic RCC Database Consortium (IMDC). Patients received sunitinib as a first-line treatment. A total of 94 patients were enrolled from 2019 to the 2020and 67 of them were included in the detailed analysis. Median progression-free survival (PFS) was 23.4 (95%CI=17.3-29.5), and median overall survival (OS) was 66 months (95%CI=44.9-87.1). The age over 60 years was a significant negative predictor for PFS and OS. Regarding the IMDC model for disease risk prediction, the number of two risk factors in the intermediate risk group was a significant predictor for a shorter response to the first-line therapy. Sunitinib is an effective tyrosine kinase inhibitor, which can be used as a first-line treatment in favorable/intermediate-risk groups of patients with mRCC, especially in countries where novel systemic treatment modalities are not yet available.

Genomic and Transcriptomic Characteristics of Tumors of Patients with Metastatic Clear Cell Renal Cell Carcinoma Clinically Benefiting from First-Line Treatment with Ipilimumab Plus Nivolumab

Background: Ipilimumab plus nivolumab is approved as a first-line treatment for intermediate or poor risk metastatic renal cell carcinoma (mRCC). However, ∼35% of patients progress within six months on ipilimumab plus nivolumab, and no validated genomic biomarkers predict the benefit. In this study, we explore the genomic and transcriptomic differences among patients with clear cell mRCC patients who either did or did not experience clinical benefit from first-line ipilimumab plus nivolumab therapy. Method: Patients with clear cell mRCC intermediate or poor IMDC risk scores, with available tumor whole exome with/without transcriptome sequencing before starting systemic therapy were included. Patients who developed a complete response, partial response, or stable disease for at least six months after initiating treatment were categorized into the ‘clinical benefit’ group, whereas the rest were classified as ‘no clinical benefit.’ Genomic alteration frequencies between the groups were assessed with a chi-square test. Differentially expressed genes and gene sets were identified via DeSeq2 and GSEA v4.2.3, respectively. Result: 53 patients with clear cell mRCC (37 clinical benefit and 16 no clinical benefit) were eligible and included. No significant difference was found in the genomic alteration frequencies between these groups. Baseline tumor transcriptomic data were available for 14 patients (9 clinical benefit and 5 no clinical benefit). The apical surface and pathways downregulated by KRAS signaling were enriched in the clinical benefit group, whereas inflammatory pathways were enriched in the no clinical benefit group. Conclusion: These findings suggest that tumor specific gene expression as assessed by RNA sequencing could serve as a potential biomarker of response to ipilimumab plus nivolumab therapy.

Real-life use of cabozantinib as front-line therapy in metastatic renal cell carcinoma: The CabFRONT (Meet-URO 24) study.

e16539 Background: Cabozantinib is approved as first-line therapy for patients with intermediate-poor risk metastatic renal cell carcinoma (mRCC); however translating results from pivotal trials to an unselected real-world population remains a concern. Methods: CabFRONT is a retrospective observational multicentre Italian Network for Research in Urologic-Oncology (Meet-URO) study of a real-life population of treatment-naïve patients with intermediate-poor mRCC treated with cabozantinib as per clinical practice between September 2019 and September 2022. Results: 209 patients were enrolled. Median age was 65 years (36 - 85). 158 patients (76%) started with a dose of 60 mg, while 51 (24%) started with a dose of 40 mg. 140 patients (67%) were classified as intermediate and 69 (33%) as poor risk according to IMDC risk model. Clear-cell represented the most common histotype (172/209), followed by papillary (19/209), chromophobe (6/209) and NOS (4/209). Sarcomatoid features were present in 29 patients (14%). Lungs were the most frequent metastatic site, [137 (65%) patients], followed by lymph nodes [115 (55%)], and bones [72 (35%)]. 33 (16%) patients presented brain metastases. At a follow-up of 23 months (mo), the median progression-free survival (mPFS) was 9.6 mo (95% CI, 7.63-10.9 mo) and the median overall-survival was 21 mo (95% CI, 14-30 mo). As best overall response, 7 patients achieved a complete response, 73 a partial response and 77 stable disease for an objective response rate (ORR) of 38% and a disease control rate (DCR) of 75%. ORR for intermediate and poor population was respectively 29% and 10%, DCR was 56% for intermediate risk and 20% for poor risk population. mPFS for intermediate and poor population was respectively 12.73 and 5.27 mo (p < 0.0001). mPFS for intermediate with 1 risk factor was 17.2 and for intermediate with 2 risk factors was 9.7 mo (p 0.0033). Subsequent antineoplastic treatments were received by 41% (86/209) of patients. Subsequent nivolumab was received by 87% of patients. 191 patients (91%) reported at least 1 grade (G) 1 to 2 adverse event (AE). The most common G1 to G2 AEs were fatigue (113 [60%]), mucositis (100 [52%]), hand-foot syndrome (HFS) (91 [47%]), diarrhoea (79 [41%]), hypertension (67 [35%]), and hypothyroidism (60 [31%]). 78 G3 AEs ere reported: the most common were fatigue (19 [24%]) and diarrhoea (18 [23%]). Permanent discontinuations from the study owing to AEs was observed in 7 patients: three for G3 diarrhea, one of which manifested also G3 renal injury, two for G3 asthenia, one for G3 HFS and one for G3 mucositis. At least 131 patients (63%) required a dose reduction and 86 (41%) required a transitory interruption to manage toxic effects. Conclusions: Our data confirmed that front-line Cabozantinib is effective and safe in an unselected real-life population of patients with intermediate-poor mRCC, including non-clear cell histologies.

Sunitinib Versus Pazopanib as Initial Therapy for Metastatic Renal Cell Carcinoma of Intermediate and Poor-Risk Characteristics: Real-World, a Single-Center

<i>Background</i>: Sunitinib and pazopanib are tyrosine kinase inhibitors (TKIs) used as first-line therapy for metastatic renal cell carcinoma (mRCC). In this study, our objective was to evaluate the effectiveness of sunitinib or pazopanib in patients with intermediate or poor risk metastatic renal cell carcinoma. <i>Methods</i>: A total of 60 patients with metastatic renal cell carcinoma were retrospectively evaluated between January 2014 and December 2020. Survival analyzes were performed with the Kaplan-Meier and log-rank tests. <i>Results</i>: Forty-six (76.7%) patients were male. Of the patients who received sunitinib, 22 patients (57.9%) were in the intermediate risk group, while 16 patients (42.1%) were in the poor risk group. Among patients receiving pazopanib, 14 patients (63.6%) were in the intermediate-risk group, while 8 patients (36.4%) were in the poor-risk group. There were no significant difference in the intermediate risk group of patients in terms of median progression-free survival between sunitinib and pazopanib (p=0.742). No significant differences were found in terms of progression-free survival in the high-risk group of patients (p=0.254). There were no significant differences in overall survival in the intermediate-risk group of patients receiving sunitinib or pazopanib (p = 0.377). There were no significant differences in terms of overall survival in the high-risk patient group receiving sunitinib or pazopanib (p = 0.3777). <i>Conclusions:</i> There were no significant difference in terms of progression-free survival and overall survival between the intermediate and poor-risk patient groups receiving pazopanib or sunitinib.

Evaluation of Provider Preferences in First-Line Metastatic Renal Cell Carcinoma: Comparison Between Dual Immunotherapy vs. Immunotherapy/Tyrosine Kinase Inhibitors

Dual immunotherapy (ipilimumab/nivolumab, IO/IO) and immunotherapy/tyrosine kinase inhibitor (IO/TKI) combinations (e.g. pembrolizumab/axitinib) are approved for the first-line treatment of intermediate/poor risk metastatic renal cell carcinoma (RCC), but there is limited comparative data between these two options. We sought to understand how oncologists decide between IO/IO vs. IO/TKI. We sent a 10-question electronic survey centered on a patient scenario of intermediate/poor risk metastatic RCC to 294 academic/disease-focused and general oncologists in the US. We received 105 responses (36% response rate): 61% (64) of providers chose IO/IO, 39% (41) chose IO/TKI. 78% (82) of oncologists were academic or disease-focused, 22% (23) were general. Academic/disease-focused oncologists were significantly more likely to choose IO/IO (56/82, 68%) than general oncologists (8/23, 35%), P=.004. Among those who chose IO/IO, the perceived main issue with IO/TKI was: long-term toxicities - 31% (20), short-term toxicities - 28% (18), less effective - 28% (18), less convenient - 8% (5). Among those who chose IO/TKI, the perceived main issue with IO/IO was: short-term toxicities - 43% (17), less effective - 28% (11), long-term toxicities - 15% (6), and risk of death - 10% (4). 88% (92) of providers would be comfortable enrolling patients into a phase III trial comparing IO/IO vs. IO/TKI. We found no associations between therapy chosen by a provider and participation as PI in a trial of IO/IO or IO/TKI, or receipt of outside funding from an IO/IO or IO/TKI company. In response to a patient scenario of intermediate/poor risk metastatic RCC, 61% of providers chose IO/IO, 39% chose IO/TKI. There was a significant association between type of practice and choice of therapy, with academic/disease-focused oncologists more likely to choose IO/IO. The majority of oncologists would be comfortable enrolling patients into a phase III trial comparing IO/IO vs. IO/TKI.

Compassionate Use Program of Ipilimumab and Nivolumab in Intermediate or Poor Risk Metastatic Renal Cell Carcinoma: A Large Multicenter Italian Study.

Simple SummaryIpilimumab and Nivolumab (IPI-NIVO) improved survival in a pivotal phase III trial conducted in patients with metastatic Renal Cell Carcinoma (mRCC) with intermediate or poor International Metastatic RCC Database Consortium (IMDC) score when compared to sunitinib. A compassionate use program of IPI-NIVO was launched in Italy from April through October 2019. The aim of our retrospective study was to assess the outcome of mRCC patients treated with IPI-NIVO within the Italian compassionate use program. Despite one third of patients not completing the induction phase of IPI-NIVO due to either toxicity or early progression, the 12-month survival rate of 66.8% confirms that IPI-NIVO combination is an effective first-line regimen for mRCC patients with IMDC intermediate-poor risk score.This is a retrospective analysis on the safety and activity of compassionate Ipilimumab and Nivolumab (IPI-NIVO) administered to patients with metastatic Renal Cell Carcinoma (mRCC) with intermediate or poor International Metastatic RCC Database Consortium (IMDC) score as a first-line regimen. IPI was infused at 1 mg/kg in combination with Nivolumab 3 mg/kg every three weeks for four doses, followed by maintenance Nivolumab (240 or 480 mg flat dose every two or four weeks, respectively) until disease progression or unacceptable toxicity. A total of 324 patients started IPI-NIVO at 86 Italian centers. Median age was 62 years, 68.2% IMDC intermediate risk. Primary tumor had been removed in 65.1% of patients. Two hundred and twenty patients (67.9%) completed the four IPI-NIVO doses. Investigator-assessed overall response rate was 37.6% (2.8% complete). Twelve-month survival rate was 66.8%, median progression-free survival was 8.3 months. Grade 3 or 4 treatment-related adverse events occurred in 67 patients (26.9%). IMDC intermediate risk, nephrectomy, BMI ≥ 25 kg/m2, and steroid use for toxicities correlated with improved survival, while age < 70 years did not. IPI-NIVO combination is a feasible and effective regimen for the first-line treatment of intermediate-poor IMDC risk mRCC patients in routine clinical practice.

A Retrospective Study of First-Line Therapy Involving Immune Checkpoint Inhibitors in Patients With Poor Risk Metastatic Renal Cell Carcinoma.

PurposePatients with International Metastatic RCC Database Consortium (IMDC) poor risk metastatic renal cell carcinoma (mRCC) rarely respond to first-line tyrosine kinase inhibitors (TKIs) including sunitinib, and carries a very poor prognosis. In recent years, combination therapy involving immune checkpoint inhibitors (ICIs) have demonstrated superior efficacy to sunitinib in poor risk disease.Materials and MethodsIn a retrospective study using a cancer chemotherapy registry, 206 consecutive patients with mRCC in the first-line setting were identified between Oct 2019 and Dec 2020. Sixty-one patients had a poor risk mRCC, and were treated with TKI monotherapy (n=36), nivolumab plus ipilimumab (n=16), or pembrolizumab plus axitinib (n=9). Endpoints included overall survival (OS), progression-free survival (PFS), response rate (RR), and safety.ResultsPatients’ median age was 61 years and the median number of risk factors was 3 (range, 3-5). During a median 23.0 months of follow-up, the median OS was 24.3 months with ICI-based combinations and 14.8 months with TKI monotherapy, and the median PFS periods were 9.3 months and 3.4 months, respectively. An objective response occurred in 60% of the patients receiving ICI-based combinations and in 19% of those receiving TKI monotherapy (P=0.001). In the multivariate regression model, number of IMDC risk factors and the ICI-based combination therapy were independent prognostic factors for PFS. All-causality grade 3 or 4 adverse events were 44% for ICI-based combinations and 50% for TKI monotherapy.ConclusionsAmong patients with poor risk mRCC, first-line ICI-based therapy showed significantly longer OS and PFS, as well as a higher RR, than TKI monotherapy.

Invited commentary: When and how to initiate systemic therapy in treating favorable risk metastatic renal cell carcinoma.

Invited commentary: When and how to initiate systemic therapy in treating favorable risk metastatic renal cell carcinoma.

Cytoreductive nephrectomy for metastatic renal cell carcinoma, the ultimate urologic 'Choosing Wisely' campaign: a narrative review.

In the early 2000s, cytoreductive nephrectomy in addition to systemic cytokines became standard of care for treating metastatic renal cell carcinoma. Since that time, the development of novel systemic targeted therapies and immuno-oncologic agents have challenged the utility of cytoreductive nephrectomy in clinical practice. In 2019, the controversial CARMENA study was published, providing the first level one evidence suggesting that cytoreductive nephrectomy combined with targeted therapy yielded no survival advantage over targeted therapy alone in intermediate and poor risk metastatic renal cell carcinoma patients. Later that year, the SURTIME trial demonstrated that patients undergoing targeted therapy with delayed nephrectomy maintained a survival advantage over those that underwent upfront cytoreductive nephrectomy followed by targeted therapy. Both of these studies underscored the importance of patient selection and timing of cytoreductive nephrectomy and systemic therapy. As new immuno-oncologic agents are trialed, particularly in combination, the role of cytoreductive nephrectomy will continue to be questioned. In this narrative review, we discuss the evolution of the role of cytoreductive nephrectomy in treating metastatic renal cell carcinoma through the context of the ever-changing landscape of targeted therapies and immuno-oncologic agents. We assess the evidence for cytoreductive nephrectomy with respect to patient factors, timing of surgery, and combination with other therapies.

Cytoreductive nephrectomy for favorable risk patients with metastatic renal cell carcinoma? Yes, cytoreductive nephrectomy should still be considered.

Cytoreductive nephrectomy for favorable risk patients with metastatic renal cell carcinoma? Yes, cytoreductive nephrectomy should still be considered.

Prognostic value of serum C-reactive protein level prior to second-line treatment in intermediate risk metastatic renal cell carcinoma patients.

e16065 Background: The later-line treatment of metastatic renal cell carcinoma (mRCC) has been drastically changing by the development of immune-oncology drugs and molecular targeted treatment in recent years. Although the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) model is useful for second-line setting, this model has the problem that over 50% patients are classified as intermediate risk group. The aim of this study is to evaluate whether the serum C-reactive protein (CRP) levels prior to second-line treatment could divide intermediate risk group patients. Methods: We retrospectively reviewed 150 mRCC patients received second-line molecular targeted therapy. We assessed the prognostic impact of serum CRP levels prior to second-line treatment initiation to predict overall survival (OS) especially in intermediate risk group. Results: The median OS from second-line treatment of whole cohort and intermediate risk group were 24.6 (95%confidence interval, 95%CI:18.2-31.0) and 23.6 (95%CI:15.1-32.1) months. Thirty-three out of 82 (40%) intermediate risk patients demonstrated elevated baseline CRP levels. The median OS of elevated and non-elevated CRP group were 13.4 (95%CI:5.9-20.8) and 29.4 (95%CI:25.5-33.5) months, respectively (p = 0.001). The serum CRP elevation could predict prognosis in intermediate risk patients treated with second-line treatment (HR 2.5,95%CI:1.4-4.2, p = 0.001). Conclusions: The serum CRP levels at second-line treatment initiation could divide intermediate risk mRCC patients into two prognostic subgroups.

Updated European Association of Urology Guidelines for Cytoreductive Nephrectomy in Patients with Synchronous Metastatic Clear-cell Renal Cell Carcinoma

Cytoreductive nephrectomy (CN) has been the standard of care in patients with metastatic clear-cell renal cancer who present with the tumour in place. The CARMENA trial compared systemic therapy alone with CN followed by systemic therapy. This article outlines the new guidelines based on these data. Patient summaryThe CARMENA trial demonstrates that immediate cytoreductive nephrectomy should no longer be considered the standard of care in patients diagnosed with intermediate and poor risk metastatic renal cell carcinoma when medical treatment is required. However, the psychological burden poor risk patients experience hearing that removal of their primary tumour will not be beneficial, should be carefully considered.

ECOG score analysis as a proxy for health-related quality of life assessment in patients with poor or intermediate risk metastatic renal cell carcinoma from the CABOSUN trial (Alliance A031203).

e18690Background: CABOSUN, a randomized and open-label phase II trial, demonstrated significant improvement in progression-free survival (PFS) with cabozantinib versus sunitinib in the first-line t...

Biomarker study of early death in patients with intermediate and favorable risk metastatic renal cell carcinoma.

530 Background: The primary objective of this study was to determine whether severe systemic inflammation (SSI) could serve as a biomarker for terminal disease progression and early death in patients with intermediate and favorable risk metastatic renal cell carcinoma (mRCC). Methods: Retrospective chart reviews of patients treated with targeted therapy for mRCC were conducted at the Winship Cancer Institute of Emory University (WCIEU) and the Atlanta Veterans Administration Medical Center (AVAMC) after obtaining institutional authorizations. The modified Glasgow Prognostic Score (mGPS) was used to quantify intensity of systemic inflammation (ISI) at baseline and at least two additional time points that were at least 10 days apart. Early death was defined as death within two years of Day 0, the first day ISI was quantified. Descriptive statistics were employed along with Kaplan-Meier survival analysis. Results: ISI was quantified 2,428 times in 135 patients at the WCIEU with a median of 16 per patient and a range of 3 to 51 versus 758 times in 46 patients at the AVAMC with a median of 12 per patient and a range of 3 to 48. Baseline risk stratification was as follows: favorable (mGPS=0), intermediate (mGPS=1) and poor (mGPS=2) with 96 (51%), 36 (19%), and 53 patients (29%) in the respective risk groups of the combined cohort (n=181). Sixty eight of the 90 patients who died in the time frame of the study did so within 2 years of Day 0. Of these early deaths, only 34 (50%) were among patients with poor risk at baseline versus 18 (26%) and 16 (24%) of the intermediate and favorable risk patients, respectively. Furthermore, 90% of these early deaths were associated with SSI as a terminal event as were 87% of all deaths in spite of the fact that 64% of poor risk patients had died as of Year 2 versus only 27% of patients in the combined group of intermediate and favorable baseline risk. Conclusions: Severe acquired systemic inflammation is a promising biomarker for terminal disease progression and early death in patients with intermediate and favorable risk mRCC. Prospective confirmatory studies are required.

Characterization of patients (pts) with poor risk metastatic renal cell carcinoma (mRCC): Results from a pooled clinical trials database.

515 Background: Survival outcomes are heterogeneous across different subsets of mRCC pts. Poor risk pts have grim outcomes and are less likely to be enrolled in clinical trials, hence the lack of prospective data characterizing this pt population. We provide a comprehensive analysis of poor risk pts, as defined by three widely used prognostic models, in the era of targeted therapy. Methods: We conducted a pooled retrospective analysis of 4,736 mRCC pts treated on phase II and III clinical trials. Pts were defined as poor risk according to the Memorial Sloan Kettering Cancer Center (MSKCC), International Metastatic Database Consortium (IMDC), and Hudes prognostic risk models. We evaluated overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and adverse events (AEs) in poor risk pts in each of the risk models in the total cohort and in a subset of pts who remained on treatment for &gt;12 months (mos). The models’ concordance (c-) index was used to assess their prognostic performance. Results: We identified 1145 (24.2%), 904 (19.1%), and 1901 (40.1%) poor risk pts by IMDC, MSKCC, and Hudes models, respectively. The majority were &lt;65 years of age (70-73%) with clear-cell histology (85-88%), prior nephrectomy (62-66%), and no prior systemic therapy (80-86%). The efficacy and toxicity outcomes as well as the c-indexes for each of the models are reported in the table below. Additionally, 9-14% of poor risk pts remained on therapy for &gt;12 mos and had higher OS (29.8-35.2 mos) and ORR (42-53%). Conclusions: In this large database of poor risk mRCC pts, we highlight that the models have similar predictive accuracy in the targeted therapy era. We also demonstrate that poor risk pts continue to have dismal outcomes and should be considered for trials of novel agents and combinations. A subset of these pts appears to derive prolonged clinical benefit and should be further explored.[Table: see text]

P139 - Comparison of sunitinib versus temsirolimus in patients with poor risk metastatic renal cell carcinoma

P139 - Comparison of sunitinib versus temsirolimus in patients with poor risk metastatic renal cell carcinoma

Activity and safety of sunitinib in poor risk metastatic renal cell carcinoma patients.

To assess the activity, safety and treatment patterns of sunitinib in patients with poor-risk metastatic renal cell carcinoma (mRCC). We retrospectively reviewed the charts of poor risk patients treated with sunitinib from October 2006 to July 2013 who met the eligibility criteria. The primary endpoint was overall survival (OS). Tumor radiological response was measured according to RECIST 1.1 and adverse events (AEs) were assessed through standard criteria. Median OS was 8.16 months (95% CI, 5.73-10.59). Of the 53 patients included in this analysis, 9 (17.0%) achieved partial response, 12 (22.6%) had stable disease. Median treatment duration was 3.30 months (95% CI: 1.96-4.63) and 26.4% of patients discontinued treatment due to toxicity. Grade 3 or higher AEs occurred in 39.6% of patients, the most common being fatigue (15.1%), neutropenia (9.5%), nausea, vomiting and diarrhea (7.5% each). Sunitinib may benefit some unselected poor-risk patients, although the rates of AEs and drug discontinuation suggest a need for careful patient monitoring.

837P - Poor Risk Metastatic Renal Cell Carcinoma (Mrcc) Patients are not a Homogeneous Group: a New Stratificating Model in the Era of Targeted Therapy

ABSTRACT Aim: The prognostic stratification of poor risk mRCC patients in the era of targeted therapy represents an unmet medical need. We analyzed, individually, each prognostic factor included in modified Memorial Sloan-Kettering Cancer Center (MSKCC) and Heng criteria to investigate their prognostic relevance in poor risk mRCC patients and proposed a model to stratify poor risk patients into 3 separate subgroups. Methods: Data were collected from 20 Italian and 2 Spanish centers. Overall survival (OS) was estimated using Kaplan-Meier method. Hemoglobin, Performance Status, Thrombocytosis, Neutrophilia, Number of metastatic sites, Time from diagnosis to treatment, LDH and Hypercalcemia, according to modified MSKCC and Heng criteria, were included in the Cox analysis. Results: 239 (151 males; 205 clear cell) poor risk mRCC pts were enrolled according to, at least, three of MSKCC, or modified MSKCC or Heng criteria. 233 pts were treated with a first line therapy (56 pts with temsirolimus, 163 pts with tyrosine kinase inhibitors (TKI), 14 pts with other agents); 101 pts with a second line (50 everolimus, 49 TKI, 2 other agents) and 31 pts with a third line ( 4 everolimus; 20 TKI, 7 other agents). Only Hemoglobin (13 vs 8 months; p = 0.005), Performance Status (14 vs 7 months; p = 0.002), and Time from diagnosis to treatment (22 vs. 8 months; p Conclusions: This is the first study that identifies three different prognostic subgroups among poor risk RCC patients. Kaplan Meier survival curves of each subgroup will be presented during the meeting. Disclosure: All authors have declared no conflicts of interest.

836P - Treatment and Outcome(S) of a Large Cohort of Poor Risk Metastatic Renal Cell Carcinoma (Prrcc) Patients (Pts)

ABSTRACT Aim: With the exception of the Temsirolimus (Tem) registration trial, prRCC is grossly underrepresented in clinical trials. Methods: We collected information on a large cohort of prRCC (239 pts) from 20 Italian and 2 Spanish centers. Results: Three prognostic models (MSKCC, modified MSKCC - mMSKCC, International Metastatic RCC Database Consortium - DC) and 8 individual risk factors (RF) were considered: multiple metastatic sites (89%), time from diagnosis to treatment (82%), and anaemia (77%) were the most frequent individual RF. Eighty-nine percent, 63%, and 61% of pts had at least 3 RF according to mMSKCC, MSKCC, and DC, respectively; mMSKCC had the best discriminating power between intermediate and prRCC (median OS: 28 vs 8 mos, respectively; p 6 mos) was 44% and was significantly higher for pts receiving first-line TKI versus Tem (50% vs 26%, p = 0.002). Age, nephrectomy status, mMSKCC, and total number of RF, but not the type of treatment received (Tem vs VEGFR-TKI), were independently associated with OS at multivariate analysis. Thirty seven percent of prRCC pts survived >12 mos (29% and 40% in pts receiving Tem and VEGFR-TKI, respectively). Basal Hb and calcium levels within normal limits were significantly associated with higher chances of achieving long-term survival upon VEGFR-TKI treatment, while a non-significant trend towards a higher proportion of long-term survivors upon Tem treatment was observed for longer time from diagnosis to treatment and normal LDH levels, in an exploratory analysis of predictive factors. Conclusions: Despite heterogeneity, prRCC may benefit from systemic treatment across multiple lines of therapy. Further prognostic/predictive stratification within the prRCC group is clearly necessary (see also the abstract by Guida et al. at this Meeting). Disclosure: All authors have declared no conflicts of interest.