Second-Line Treatment Outcomes After First-Line Sunitinib Therapy in Metastatic Renal Cell Carcinoma

This study was conducted to evaluate the treatment outcomes associated with common second-line targeted therapies given after first-line sunitinib for metastatic renal cell carcinoma (mRCC). The sample comprised patients with mRCC (n = 257) who were receiving second-line everolimus, sorafenib, or temsirolimus between April 1, 2008, and February 29, 2011, after first-line sunitinib treatment. The patients were followed-up from the start of second-line treatment until treatment failure (defined as advancement to a third-line therapy or to mortality) or the last observation in the medical and pharmacy databases. Treatment failure was observed in 38.5% (n = 99) of cases: 20.2% of patients (n = 52) advanced a line of treatment; and 18.3% of patients (n = 47) died. Kaplan-Meier analysis indicated a statistical difference in time to treatment failure among the 3 second-line targeted therapies (log-rank test, P = .045). The estimated 1-year cumulative probabilities of treatment failure were 49.9% for everolimus, 68.4% for sorafenib, and 71.4% for temsirolimus. In a multivariate Cox proportional hazards model, a higher adjusted risk of treatment failure vs. everolimus was observed for both temsirolimus (hazard ratio [HR] 2.05 [95% CI, 1.26-3.35]; P = .004) and sorafenib (HR 1.77 [95% CI, 1.02-3.07]; P = .043). The results of this real-world data analysis suggest that the risk of second-line treatment failure after first-line sunitinib was significantly higher with temsirolimus and sorafenib compared with everolimus.     

Prognostic Value of Hematologic Parameters in Patients with Metastatic Renal Cell Carcinoma Using Tyrosine Kinase Inhibitors

Background: The prognostic significance of the neutrophil-to-lymphocyte ratio for progression free survivalin patients with metastatic renal cell carcinoma is unclear. Materials and Methods: We retrospectively reviewed45 patients diagnosed with metastatic RCC previously treated with tyrosine kinase inhibitors from two centers,Akdeniz University Hospital and Afyon Kocatepe University. The prognostic value of the pretreatment neutrophiltolymphocyteratio, and other clinical and laboratory parameters were assessed by univariate and multivariateanalysis. Results: Median progression free survival (PFS) was 13.9 months [95% CI for HR (6.88-20.91)] andoverall survival figure of 16.6 months [95% CI for HR (7.23-26.03)] Univariate analysis revealed that PFS wassignificantly affected by hemoglobin level [p=0.013 (95% CI for HR (0.71-0.96))], eosinophil count [p=0.031(95% CI for HR (0.20-0.92))], ratio of neutrophil lymphocytes (NLR) [p=0.007 (95% CI for HR (1.47-11.74))]and calcium level [p=0.006 (95% CI for HR (0.15-0.73))]. However, only NLR [p=0.031 (95% CI for HR (1.15-18.1))] and calcium levels [p=0.018 (95% CI for HR (0.20-18.1))] retained significance with multivariate analysis.Median PFS was 23.9 vs 8.6 months in patients with NLR ≤2 vs NLR >2 (Log rank; p= 0.040). Conclusions: Thisstudy showed that increased pretreatment NLR is an independent prognostic factor for patients with metastaticRCC using tyrosine kinase inhibitors.     

Cytoreductive Nephrectomy in Metastatic Clear‐Cell Renal Cell Carcinoma: Perspectives in the Tyrosine Kinase Inhibitor Era

Cytoreductive nephrectomy in combination with adjuvant immunotherapy is an established treatment option for selected patients with metastatic clear‐cell renal cell carcinoma (mCC‐RCC). Multitargeted antiangiogenic and mammalian target of rapamycin tyrosine kinase inhibitors (TKIs) are now established treatment paradigms in patients with mCC‐RCC. Given that all the recent seminal TKI trials in mCC‐RCC provide no evidence base for the use of cytoreductive nephrectomy in the TKI era, it is not presently clear where such a surgical approach fits into the treatment paradigm. This review summarizes the evidence for the management of mCC‐RCC and outlines novel approaches to be tested within future trials if the initial proposed phase III trials in this setting, using sunitinib, are successful. Overall, two principal questions need addressing. First, is cytoreductive nephrectomy necessary in the TKI era? Second, if so, what is the most appropriate scheduling of TKI therapy with cytoreductive nephrectomy?     

Prognostic Factors of Survival for Patients With Metastatic Renal Cell Carcinoma With Brain Metastases Treated With Targeted Therapy: Results From the International Metastatic Renal Cell Carcinoma Database Consortium

BackgroundThe outcomes and prognosis of patients with brain metastases from advanced renal cell carcinoma (RCC) are not well characterized in the targeted-therapy era.MethodsData from patients with metastatic RCC (mRCC) and brain metastases treated with targeted therapy were collected through the International Metastatic Renal Cell Carcinoma Database Consortium from 7 cancer centers.ResultsOverall, 106 (15%) of 705 patients with mRCC had brain metastases. Forty-seven patients had brain metastases at the start of first-line anti–vascular endothelial growth factor therapy, and the rest developed metastases during follow-up. Of the patients with brain metastases, 12%, 42% and 29% were in the favorable, intermediate, and poor prognosis groups, respectively, per the Heng criteria. Ninety percent had cerebral metastases, 17% had cerebellar metastases, 37% had a Karnofsky performance status (KPS) <80%, and 80% had neurologic symptoms at presentation. The median largest size and number of brain metastases was 1.8 cm (range, 0.2-6.6 cm) and one (range, 1 to innumerable), respectively. The patients were treated with sunitinib (n = 77), sorafenib (n = 23), bevacizumab (n = 5), and temsirolimus (n = 1). Local disease treatment included whole brain radiotherapy (81%), stereotactic radiosurgery (25%), and neurosurgery (25%). On multivariable analysis, KPS < 80%, diagnosis to treatment with targeted therapy <1 year, and a higher number of brain metastases (>4) was associated with worse survival from the time of diagnosis with brain metastases.ConclusionsPatients with brain metastases from RCC are unlikely to be in the favorable risk group. KPS at the start of therapy, diagnosis to treatment time, and the number of brain metastases are prognostic factors for overall survival.     

Disease Flare After EGFR Tyrosine Kinase Inhibitor Cessation Predicts Poor Survival in Patients with Non-small Cell Lung Cancer

Available study revealed non-small cell lung cancer (NSCLC) patients faced a risk of disease flare after cessation of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) treatment. There was no data concerning the prognostic value of disease flare. This study aimed to investigate the prevalence of disease flare in a Chinese cohort, and analyzed its prediction to survival. A cohort of 227 NSCLC patients with acquired resistance to EGFR TKI was retrospectively analyzed. Prevalence and clinical features of disease flare after TKI cessation were reviewed. Survival data were analyzed between patients with flare and those without flare. EGFR gene mutations in tumors were detected. Twenty of 227 (8.8 %) patients were determined with disease flare after TKI cessation. The median interval from TKI cessation to disease flare was 7 days (range 3–18). Forty percent of patients complained of deteriorated dyspnea attributable to malignant effusion. Thirty percent of patients had progressive lesions in the brain. After TKI cessation 35 % of flare patients died before challenge of subsequent treatment. No response was observed in 30 % of flare patients undergoing subsequent chemotherapy. When compared with the non-flare group, patients with disease flare demonstrated comparable progression-free survival (10.1 vs. 9.9 months; P?=?0.973), shorter post-TKI survival (4.1 vs. 6.1 months; P?<?0.001), and a significantly poor overall survival (16.6 vs. 21.6 months; P?=?0.002). Disease flare after cessation of EGFR TKI occurred in Chinese NSCLC population and predicted a poor survival.     

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

IntroductionDual 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.MethodsWe 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.ResultsWe 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.ConclusionIn 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.     

First-Line Treatments for Metastatic Clear Cell Renal Cell Carcinoma: An Ever-Enlarging Landscape

Treatment paradigm for metastatic clear cell renal cell carcinoma (mccRCC) has changed dramatically over the recent decades. From cytokines, interleukin-2 and interferon-α to tyrosine kinase inhibitors and mammalian target of rapamycin inhibitors, during the last decade, combinations of immune checkpoint inhibitors have taken over first-line treatment of mccRCC. These combinations are approved based on results from large phase III clinical trials, all of which used sunitinib as the comparator. These trials include CheckMate214 (ipilimumab plus nivolumab), KEYNOTE 426 (pembrolizumab plus axitinib), JAVELIN Renal 101 (avelumab plus axitinib), CheckMate 9ER (nivolumab plus cabozantinib), and the CLEAR study (lenvatinib and pembrolizumab). Results from these studies constitute milestones for newer therapeutic approaches in mccRCC. The broadening spectrum of treatment options for patients with mccRCC with multiple first-line options currently available also means that treating physicians will need to consider each option carefully, balance clinical factors, financial considerations, and weigh toxicity profiles of each drug before deciding the optimal treatment regimen for each individual patient. We describe each frontline treatment option in detail through this review to aid the decision-making process.     

Effect of Changes in Skeletal Muscle Mass on Oncological Outcomes During First-Line Sunitinib Therapy for Metastatic Renal Cell Carcinoma

Background

Sarcopenia is a state of degenerative skeletal muscle wasting induced by cancer cachexia.

Objective

To evaluate the prognostic impact of changes in skeletal muscle mass (SMM) during first-line sunitinib therapy on oncological outcomes in metastatic renal cell carcinoma (mRCC).

Patients and Methods

Sixty-nine patients were evaluated retrospectively. The skeletal muscle index (SMI) was calculated based on computed tomography images obtained before the initiation (pre-treatment SMI) and after two cycles of sunitinib treatment (post-treatment SMI). The change in SMM was evaluated based on the value of ΔSMI, which was calculated as [(posttreatment SMI – pretreatment SMI)/ pretreatment SMI]?×?100. Oncological outcomes were compared between patients with ΔSMI <0 (SMM decrease) and ΔSMI ≥0 (SMM maintenance).

Results

A decrease in SMM was observed in 38 patients (55.1%). Progression-free survival (PFS) and overall survival (OS) after sunitinib therapy initiation were significantly shorter in patients with ΔSMI <0 than in those with ΔSMI ≥0 (median PFS: 9.53 vs. 28.4 months, p?<?0.0001; OS: 19.8 vs. 52.6 months, p?=?0.0001). ΔSMI was an independent predictive factor for PFS (HR 3.25, 95% CI 1.74–6.29, p?=?0.0002) and OS (HR 4.53, 95% CI 2.15–10.5, p?<?0.0001). The objective response rate was significantly lower in patients with ΔSMI <0 than in those with ΔSMI ≥0 (23.7% vs. 51.6%, p?=?0.0164).

Conclusion

Decreased SMM during first-line sunitinib therapy can be an effective marker of outcome prediction for mRCC.

     

Expert Recommendations for First-Line Management of Metastatic Renal Cell Carcinoma in Special Subpopulations

The availability of agents targeting the vascular endothelial growth factor or mammalian target of rapamycin [mTOR] pathways has provided new treatment options for patients with metastatic renal cell carcinoma (RCC). Based on the results of pivotal randomized clinical trials, specific recommendations have been established for management of these patients in first- and second-line settings. However, certain subgroups of patients may be excluded or under-represented in clinical trials, including patients with poor performance status, brain metastases, and cardiac or renal comorbidities, elderly patients, and those with non-clear cell histology. For these subpopulations, management recommendations have emerged from expanded access programs (EAPs), small phase II studies, retrospective analysis of clinical data, and expert opinion. This paper describes recommendations from an expert panel for the treatment of metastatic RCC in these subpopulations. The efficacy of targeted agents appears to be inferior in these patient subgroups relative to the general RCC population. Tyrosine kinase inhibitors (TKIs) and mTOR inhibitors can be administered safely to elderly patients and those with poor performance status, although dose and schedule modifications are often needed, and close monitoring and management of adverse events is essential. In addition to local surgical treatment and radiotherapy for brain metastases, systemic treatment with a TKI should be offered as part of multidisciplinary care.While there are currently no data from randomized trials, sunitinib has the greatest body of evidence, and it should be considered the first choice in patients with a good prognosis. Patients with an acute cardiac event within the previous 6 months, New York Heart Association grade III heart failure, or uncontrolled high blood pressure should not be treated with TKIs. In patients with mild or moderate renal failure, there are no contraindications to TKI treatment. TKIs can be administered to patients undergoing dialysis, but other, less nephrotoxic agents and other alternatives should always be considered.

In managing RCC among patients with non-clear cell histology, sunitinib seems to be more effective than everolimus for the papillary subtype, but there are no clear data to guide treatment for other subtypes. In conclusion, individualized treatment approaches are needed to manage RCC in subpopulations that are underrepresented in registration clinical trials.

Open image in new window

     

Sarcopenia and the Modified Glasgow Prognostic Score are Significant Predictors of Survival Among Patients with Metastatic Renal Cell Carcinoma Who are Receiving First-Line Sunitinib Treatment

Background

Cancer cachexia is associated with patient outcomes.

Objective

The objective was to evaluate the effect of cachexia on survival among patients with metastatic renal cell carcinoma (mRCC) who had received first-line sunitinib treatment.

Patients and Methods

Seventy-one patients were retrospectively evaluated. Sarcopenia was diagnosed using sex-specific cut-offs for skeletal muscle index (measured using pre-treatment computed tomography) that were adjusted for body mass index. The modified Glasgow prognostic score (mGPS) was measured using C-reactive protein (CRP) and albumin levels (mGPS 2: CRP >1.0 mg/dL and albumin <3.5 g/dL; mGPS 1: CRP >1.0 mg/dL; mGPS 0: CRP ≤1.0 mg/dL). Progression-free survival (PFS) and overall survival (OS) were analyzed using the Kaplan-Meier method and Cox proportional hazard models.

Results

Forty-five patients (63.4 %) had sarcopenia, with 53 (74.6 %), ten (14.1 %), and eight (11.3 %) patients having an mGPS of 0, 1, and 2, respectively. Sarcopenia was associated with significantly inferior PFS and OS, compared to non-sarcopenic patients (PFS: 7.6 vs. 18.2 months, p?=?0.0004; OS: 22.3 months vs. not reached, p?=?0.0019). Higher mGPS was associated with inferior PFS and OS (mGPS 0, 1, and 2: PFS?=?11.5, 10.9, and 4.12 months, p?<?0.0001; OS?=?47.2, not reached, and 5.28 months, p?<?0.0001; respectively). Sarcopenia was an independent predictor of shorter PFS (p?=?0.0163), and mGPS was an independent predictor of shorter OS (p?=?0.0012).

Conclusion

Sarcopenia and mGPS can predict outcomes among patients with mRCC who are receiving first-line sunitinib treatment.

Open image in new window

     

Long-Term Response to Sunitinib Therapy for Metastatic Renal Cell Carcinoma

BackgroundSunitinib achieves objective response and prolongs progression-free survival (PFS) in patients with metastatic renal cell carcinoma (RCC). A subset of patients achieves long-term responses. The characteristics of patients who achieved long-term response (defined as patients achieving ongoing complete response [CR] or remaining progression free for > 18 months while receiving sunitinib) are reported.Patients and MethodsA database of 186 patients treated with sunitinib alone (n = 89) or in combination (n = 97) in 9 clinical trials was reviewed; all had 1 year or more follow-up from sunitinib start to data cutoff for analysis. Median PFS was 10.8 months (95% CI, 8.3-13.3); median overall survival (OS) was 30.4 months (95% CI, 21.5-36.8 months) for the 186 patients. Thirty-four patients were identified as long-term responders because they either had durable CR or remained progression free while receiving sunitinib for > 18 months.ResultsBest response for 34 long-term responders was CR in 3 patients, partial response (PR) in 24 patients, and stable disease in 7 patients. The median duration of sunitinib therapy was 24.9 months (range, 18.1-73.9 months). The median PFS among the long-term responders was 17.4 months (95% CI, 7-29.9 months) at a landmark PFS analysis performed after 18 months from treatment start. Univariate analysis from the 186 patients identified bone metastasis, lung metastasis, and intermediate/poor risk groups as adverse prognostic factors for long-term response.ConclusionSunitinib achieves long-term response in a subset of patients with metastatic RCC. Lack of bone metastasis or lung metastasis and good MSKCC risk status may predict long-term response.     

Assessing Outcomes and Prognostic Factors for First-Line Therapy in Elderly Patients With Metastatic Renal Cell Carcinoma: Real-Life Data From a Single United Kingdom Institution

BackgroundElderly metastatic renal cell carcinoma (mRCC) patients are under-represented in clinical trials, whose results are therefore difficult to translate into routine management of older patients. We aimed at exploring treatment outcomes and prognostic factors in our real-life elderly mRCC cohort receiving first-line tyrosine kinase inhibitor (TKI) monotherapy.Patients and MethodsWe retrospectively analyzed demographic and clinicopathological characteristics, and treatment data of elderly (≥ 70 years old at first-line start) mRCC patients starting either pazopanib or sunitinib as first-line treatment in our institution between March 2012 and April 2018. Baseline characteristics included age-adjusted Charlson comorbidity index (CCI).ResultsIn total, the records of 35 elderly mRCC patients were identified and retrospectively analyzed. Overall response rate, median progression-free survival, and median overall survival were 20%, 9.7 months, and 21.6 months, respectively. Karnofsky performance status ≤ 70%, sarcomatoid features, absolute neutrophil count greater than upper limit of normal, and treatment-related Grade 3 arterial hypertension were independently associated with survival after multivariate analysis. Age-adjusted CCI was significantly associated with survival in univariate analysis only. The overall incidence of Grade 3 to 5 toxicities was 74%. Seven patients (20%) received early crossover to either sunitinib or pazopanib because of toxicity. Dose reduction was applied in 24 (73%) of the 33 patients who completed at least 1 cycle.ConclusionFirst-line TKI monotherapy provided clinical benefit in our elderly mRCC cohort. Relatively frequent dose reductions helped to maintain an acceptable tolerability profile. Further research is warranted to explore the significance of prognostic factors in elderly mRCC patients.     

Correlation of c-MET Expression with PD-L1 Expression in Metastatic Clear Cell Renal Cell Carcinoma Treated by Sunitinib First-Line Therapy

Background

Clear cell renal cell carcinoma (ccRCC) is highly metastatic. Cabozantinib, an anti-angiogenic tyrosine kinase inhibitor that targets c-MET, provided interesting results in metastatic ccRCC treatment.

Objective

To understand better the role of c-MET in ccRCC, we assessed its status in a population of patients with metastatic ccRCC.

Patients and Methods

For this purpose, tumor samples were analyzed for c-MET expression by immunohistochemistry (IHC), for c-MET copy number alterations by fluorescence in situ hybridization (FISH), and for c-MET mutations by next generation sequencing (NGS) in a retrospective cohort of 90 primary ccRCC of patients with metastases treated by first-line sunitinib. The expression of c-MET was correlated with pathological, immunohistochemical (VEGFA, CAIX, PD-L1), clinical, and molecular criteria (VHL status) by univariate and multivariate analyses and to clinical outcome using Kaplan-Meier curves compared by log-rank test.

Results

Of ccRCC, 31.1% had low c-MET expression (absent to weak intensity by IHC) versus 68.9% with high expression (moderate to strong intensity). High expression of c-MET was associated with a gain in FISH analysis (p=0.004), sarcomatoid component (p=0.037), and PD-L1 (p<0.001) after logistic regression. No difference was observed in clinical outcomes.

Conclusion

This study is the first to analyse c-MET status in metastatic ccRCC. The high expression of c-MET in the majority of ccRCC and its independent association with PD-L1 expression, may suggest a potential benefit from combining c-MET inhibitors and targeted immunotherapy.

Open image in new window

     

转移性肾细胞癌分子靶向治疗研究进展

肾细胞癌是泌尿系统肿瘤中常见的恶性肿瘤,发病率约5～10/10万。转移性肾细胞癌在以细胞因子为基础的治疗失败后,尚无明确的二线治疗措施。随着对乏氧诱导因子(hypoxia-inducible factor,HIF)相关蛋白的研究,转移性肾细胞癌分子靶向治疗研究成为热点。本文综述较有前景的靶向药物,包括Bevacizumab(贝伐单抗)、Sorafenib(索拉非尼)、Sunitinib(舒尼替尼)、AG-013736、Vatalanib(PTK787)、Thalidomide(沙利度胺)及Temsirolimus(CCI-779)。     

Factors Prognostic for Survival in Japanese Patients Treated with Sunitinib as First-line Therapy for Metastatic Clear Cell Renal Cell Cancer

Background: Factors predictive of survival have been identified in Western patients with metastatic clearcell renal cell carcinoma (mCCRCC) treated with sunitinib. Less is known, however, about factors predictiveof survival in Japanese patients. This study evaluated factors prognostic of survival in Japanese patients withmCCRCC treated with first-line sunitinib. Materials and Methods: This retrospective study evaluated 46consecutive Japanese mCCRCC patients treated with sunitinib as first line therapy. Clinical and biochemicalmarkers associated with progression-free survival (PFS) were analyzed, with prognostic factors selected by uniandmultivariate Cox regression analyses. Results: Univariate analysis showed that factors significantly associatedwith poor PFS included Memorial Sloan-Kettering Cancer Center poor risk scores, International MetastaticRCC Database Consortium poor risk and high (>0.5 mg/dl) serum C-reactive protein (CRP) concentrations(p<0.001 each). Multivariate analysis showed that high serum CRP was independently associated with poorerPFS (p=0.040). Six month disease control rate (complete response, partial response and stable disease) in responseto sunitinib was significantly higher in patients with normal (≤0.5 mg/dl) than elevated baseline CRP (p<0.001).Conclusions: CRP is a significant independent predictor of PFS for Japanese patients with mCCRCC treatedwith first-line sunitinib. Pretreatment CRP concentration may be a useful biomarker predicting response tosunitinib treatment.     

First-Line Mammalian Target of Rapamycin Inhibition in Metastatic Renal Cell Carcinoma: An Analysis of Practice Patterns From the International Metastatic Renal Cell Carcinoma Database Consortium

Introduction/BackgroundApproval of the mTOR inhibitors for the treatment of mRCC was based on efficacy in poor-risk patients in the first-line setting for temsirolimus and in vascular endothelial growth factor inhibitor-refractory patients for everolimus. We strove to characterize temsirolimus and everolimus use and effectiveness in the first-line setting.Patients and MethodsWe performed a retrospective database analysis of mRCC patients who received mTOR inhibitors as first-line targeted therapy. The Kaplan-Meier product-limit method was used to estimate the distribution of progression-free survival (PFS) and overall survival (OS).ResultsWe identified 127 mRCC patients who had received a first-line mTOR inhibitor. Temsirolimus was administered in 93 patients (73%) and everolimus in 34 patients (27%). The main reasons for choice of temsirolimus were poor-risk disease (38%), non-clear cell histology (27%), and clinical trial availability (15%), whereas clinical trial (82%) and non-clear cell histology (6%) drove everolimus selection. Of the temsirolimus and everolimus patients, 58% and 32% were poor-risk according to the International mRCC Database Consortium criteria, respectively. The median PFS and OS were 3.4 and 12.5 months and 4.8 and 15.9 months with temsirolimus and everolimus, respectively. Although limited by small numbers, this study characterizes a real-world, international experience with the use of mTOR inhibition in treatment-naive mRCC patients.ConclusionPoor-risk RCC, non-clear cell histology, and clinical trials were the predominant reasons for mTOR inhibitor selection in the front-line setting. Because of the different patient populations in which they were administered, direct comparisons of the front-line efficacy of temsirolimus and everolimus cannot be made.     

Novel Predictive Models of Early Death Less Than 1 Year in Patients With Metastatic Renal Cell Carcinoma After Treatment With First-line Tyrosine Kinase Inhibitors

BackgroundWe aimed to develop a modified International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) model that can predict early death less than 1 year in patients with metastatic renal cell carcinoma (mRCC) after receiving first-line tyrosine kinase inhibitors (TKIs).Patients and MethodsWe retrospectively reviewed records of patients with mRCC treated with first-line TKIs at our institution between 2007 and 2012. The primary endpoint was the rate of early death within 1 year after first-line TKI administration. We determined statistically significant factors predicting early death by performing multiple logistic regression. The modified IMDC model 1 was developed using new variables in addition to the risk criteria of the IMDC model, and model 2 was developed using new variables irrespective of the risk classification of IMDC model.ResultsEarly mortality within 1 year of first-line TKI treatment was 19.7% (n = 98) in 462 patients. Although the C-index of the IMDC model for early death was 0.655, the C-index of model 1, which includes 5 variables (previous nephrectomy, body mass index, multiple metastases, previous metastasectomy, and serum albumin level) in addition to the Heng criteria, was 0.823. The C-index of model 2, which includes 7 variables (hemoglobin, neutrophil level, and the 5 variables of model 1) was 0.822. Of note, there was no significant difference in net reclassification index between the 2 models.ConclusionThis is the first study suggesting novel prediction models for early death less than 1 year in patients with mRCC treated with first-line TKI.