Categories of response to first line vascular endothelial growth factor receptor targeted therapy and overall survival in patients with metastatic renal cell carcinoma

IntroductionSequential use of targeted therapy (TT) has improved overall survival (OS) of patients with metastatic renal cell carcinoma (mRCC). The value of objective response (OR) as compared to stable disease (SD) is unclear. We aimed to investigate OR of first-line TT and its impact on OS.Material and methodsRetrospective analysis of OS among 331 mRCC patients with a first-line assessment according to RECIST 1.0. Characteristics between objective responders (complete response [CR] or partial remission [PR]), patients with SD and non-responders (progressive disease [PD] and toxicity [Tox]) were compared with the Chi-square test and the Kruskal–Wallis test. Kaplan–Meier analysis of OS and progression-free survival (PFS). Cox model analysis of Predictors of OS .ResultsBest response was CR, PR, SD, PD and Tox in 9 (2.7%), 61 (18.4%), 167 (50.5%), 80 (24.2%) and 14 (4.2%) patients respectively resulting in an OR rate of 21%. Median OS in months: CR 63.2; PR 37.6; SD 35.9; PD 14.6; TOX 22.5 (p < 0.0001). Median PFS for responders was 14.8, 11.5 for patients with SD and 2.5 for non-responders (p < 0.0001). Similarly median OS was 38.7, 35.9 and 15.5 (p < 0.00001). Primary resistance and a first-line PFS <6 months were the strongest independent predictors of OS. The achievement of OR as compared to SD did not impact OS.ConclusionsIn our cohort of unselected patients OR was not associated with superior OS as compared to SD.     

Efficacy and toxicity of sunitinib in patients with metastatic renal cell carcinoma with renal insufficiency

BackgroundPatients with metastatic renal cell carcinoma (mRCC) with renal insufficiency are generally excluded from clinical trials, despite their increasing numbers. Thus, we evaluated the efficacy and toxicity of sunitinib in such patients.Patients and methodsKorean patients with mRCC with renal insufficiency who had received sunitinib as first-line treatment between January 2008 and May 2012 were included. Patient characteristics, clinical outcomes and toxicities were evaluated. Overall survival (OS) and progression-free survival (PFS) were determined according to the degree of renal impairment.ResultsThe median age of the 34 patients evaluated was 66 years, 90% had an Eastern Cooperative Oncology Group performance status of 0 or 1 and the median glomerular filtration rate was 46.5 mL min⁻¹·1.73 m⁻² (range, 21.1–59.5). The starting sunitinib dose was 37.5 and 50 mg for 12 and 22 patients, respectively. A 4-weeks-on–2-weeks-off regimen was followed for 31 patients; a 2-weeks-on–2-weeks-off regimen, for one patient; and a daily regimen, for two patients. The best response was partial response in eight patients and stable disease in 12. Median OS and PFS times were 26.3 months (95% confidence interval [CI]: 17.1–35.3) and 12.2 months (95% CI: 10.2–13.2), respectively. Common non-haematologic adverse events (AEs) were stomatitis, rash, general oedema and fatigue. The most common AEs of ⩾grade 3 severity were fatigue, neutropenia and thrombocytopenia.ConclusionsIn patients with mRCC with renal insufficiency, sunitinib was efficacious and did not cause increased toxicity. Thus, clinicians should not hesitate to treat patients with mRCC with renal insufficiency with sunitinib.     

Efficacy of sunitinib in patients with metastatic or unresectable renal cell carcinoma and renal insufficiency

AimThe aim of this retrospective, registry-based study was to analyse treatment outcomes in patients with metastatic renal cell carcinoma (mRCC) treated with sunitinib and renal insufficiency (RI).MethodsThe cohort included 790 patients treated with sunitinib between 2006 and 2013. At the start of sunitinib therapy 22, 234, and 534 patients had severe (glomerular filtration rate [GFR] <30 ml/min/1.73 m²), moderate (GFR 30–60 ml/min/1.73 m²) or mild RI/normal renal function (GFR >60 ml/min/1.73 m²), respectively.ResultsFor the three groups defined above, median progression-free survival (PFS) (95% confidence interval [CI]) was 5.3 months (0.1–18.5), 8.1 months (6.2–9.9) and 11.3 months (9.4–13.2) (p = 0.244), and median overall survival (OS) was 26.3 months (1.2–51.4), 21.2 months (13.2–29.1) and 26.3 months (22.6–29.9) (p = 0.443), respectively. The disease control rates were 45.5%, 56.4% and 59.2%, respectively (p = 0.374). No unexpected toxicity was reported in the patients with RI, but the treatment was more frequently discontinued because of adverse events and the duration of therapy was significantly shorter in these patients (p = 0.007).ConclusionsDuration of first-line targeted treatment for mRCC was significantly shorter for patients with RI, and may have translated into a trend to shorter PFS. These results highlight the need for optimal management of side-effects in patients with mRCC and RI.     

Evolving options for the treatment of metastatic breast cancer: progression-free survival as an endpoint

Because of its direct clinical relevance, overall survival is the gold standard endpoint for measuring clinical efficacy. However, achieving improvements in overall survival can be confounded by factors such as crossover to active treatment arms and subsequent treatment with non-experimental active therapies. Powering studies to detect significant overall survival increases requires prohibitively large patient numbers and long follow-up and may not always be practical. Trials incorporating progression free survival (PFS) or time to progression (TTP) as primary outcome measures are likely to be shorter, require fewer patients and are usually more affordable, which may ultimately translate into a more rapid evaluation of potentially effective experimental therapies. In heavily pretreated metastatic breast cancer, significant improvements in progression-free survival may indicate a clinically meaningful benefit for patients with otherwise limited salvage therapy options available. Approval for several newer agents in the advanced resistant or refractory metastatic breast cancer setting has been based on prolonged progression-free survival or time to progression as primary trial endpoints. In this paper, clinical trial data relating to OS, PFS and TTP endpoints are reviewed and the use of surrogate markers of survival for the evaluation of new drugs is considered.     

Progression-free survival as a predictor of overall survival in metastatic renal cell carcinoma treated with contemporary targeted therapy

BACKGROUND.

The majority of metastatic renal cell carcinoma (mRCC) clinical trials that examined targeted agents used progression‐free survival (PFS) as the primary endpoint. Whether PFS can be used as a predictor of overall survival (OS) is unknown.

METHODS.

Patients from 12 cancer centers who received targeted therapy for mRCC were identified. Landmark analyses for progression at 3 months and 6 months after drug initiation were performed to minimize lead‐time bias. A proportional hazards model was used to assess the utility of PFS for predicting OS.

RESULTS.

In total, 1158 patients were included. The median follow‐up was 30.6 months, the median age was 60 years, and the median Karnofsky performance status was 80%. For the entire cohort, the median PFS was 7.6 months, and the median OS was 19.7 months. In the landmark analysis, the median OS for patients who progressed at 3 months was 7.8 months compared with 23.6 months for patients who did not progress (log‐rank test; P < .0001). Similarly, for patients who progressed at 6 months, the median OS was 8.6 months compared with 26 months for patients who did not progress (P < .0001). Compared with those who did not progress, for the patients who progressed at 3 months and at 6 months, the hazard ratios for death adjusted for adverse prognostic factors were 3.05 (95% confidence interval, 2.42‐3.84) and 2.96 (95% confidence interval, 2.39‐3.67), respectively. Similar results were demonstrated with landmark analyses at 9 months and at 12 months and in the bootstrap validation. Kendall tau rank correlation and a Fleischer model demonstrated a statistically significant dependent correlation.

CONCLUSIONS.

PFS at 3 months and at 6 months predicted OS, and the current results indicated that PFS may be a meaningful intermediate endpoint for OS in patients with mRCC who receive treatment with novel agents. Cancer 2011;. © 2010 American Cancer Society.     

舒尼替尼治疗肾细胞癌的新进展

肾细胞癌（ｒｅｎａｌｃｅｌｌｃａｒｃｉｎｏｍａ,ＲＣＣ）是最常见的肾脏肿瘤,其发病率呈逐年上升趋势,近年来随着ＲＣＣ增殖分子机制研究的深入和新的分子靶向药物不断问世,ＲＣＣ患者的生存率及生活质量均得到显著提高,ＲＣＣ的治疗进入了分子靶向时代。更重要是的,多靶点药物舒尼替尼已经取代传统的ＩＦＮ被列为转移性ＲＣＣ的一线标准治疗药物,联合分子靶向治疗与免疫治疗将是未来的发展方向。本文就舒尼替尼治疗ＲＣＣ的研究现状及进展作一综述。     

CXCR4 expression in patients with high-risk locally advanced renal cell carcinoma can independently predict increased risk of disease progression and poor overall survival

Aims and background: CXC receptor 4 (CXCR4), one of chemokine receptor family, plays important roles in metastasis of solid malignancies. In the present study, we aimed to investigate the potential predictive value of CXCR4 in the metastasis of patients with high-risk locally advanced renal cell carcinoma (LARCC). Materials and Methods: From 2001 to 2005, the expression of CXCR4 in 117 high-risk LARCCs was evaluated with immunohistochemical staining and assessed for correlations with clinical characteristics, progression-free survival (PFS) and overall survival (OS) of the patients. Results: Mean duration of follow-up was 51 months. 4-year PFS and OS of patients was 55.6% and 69.2%, respectively. High expression of CXCR4 was associated with not only increased risk for disease progression (p=0.001), but also worse OS of high-risk LARCC patients (p=0.001). Further analysis also suggested that CXCR4 expression had a significant negative predictive value for the effect of interferon alpha (IFN-α) on PFS (p=0.003). Conclusions: CXCR4 is a novel biomarker for prognosis in high-risk LARCC, which might furthermore have promise to predict clinical response to adjuvant therapy.     

Treatment of metastatic renal cell carcinoma

Purpose  To review the treatment of metastatic renal cell carcinoma (RCC), including the use of new targeted therapies. Methods  A search of MEDLINE (1966 to August 2008) and American Society of Clinical Oncology Meeting abstracts (2005 to May 2008) was preformed using the search terms bevacizumab, everolimus, interferon-alfa (IFN-α), interleukin-2 (IL-2), sorafenib, sunitinib, temsirolimus, and RCC. Articles most pertinent to the treatment of metastatic RCC are reviewed. Results  The treatment of metastatic RCC has undergone a paradigm shift over the past 5 years from biologic response modifiers to new targeted therapies. Historically, response rates for the biological response modifiers, aldesleukin (IL-2), and IFN-α were approximately 15%. Recently, three targeted agents, sorafenib, sunitinib, and temsirolimus have been approved for the treatment of RCC. Additionally, bevacizumab has been investigated and shown to increase progression free survival in RCC. IL-2 remains the only agent to induce complete, durable remissions; however, many patients are not eligible for this therapy. Newer agents (sorafenib, sunitinib, and temsirolimus) have shown to be superior to IFN-α or placebo and bevacizumab combined with IFN-α has shown activity when compared to IFN-α alone. Unlike IL-2, the greatest benefit obtained with targeted therapies is in achieving stable disease (SD). Despite their benefit, targeted therapies have never been compared with each other in clinical trials and choosing the most appropriate agent remains challenging. To date, the optimal sequence or combination of treatments has not been defined; however, everolimus has recently demonstrated activity in patients progressing on targeted therapy. Conclusions  IL-2 remains the most active regimen in inducing complete responses; however, its use is accompanied by substantial morbidity and is limited to those with a good performance status. Targeted therapies are also efficacious in the treatment of RCC, with the major benefit being induction of SD. Future research will better define the sequencing of therapies, as well as, explore the activity of novel combination regimens.     

Statins and survival outcomes in patients with metastatic renal cell carcinoma

BackgroundA growing body of evidence has demonstrated the anti-neoplastic activity of statins. The objective of this study was to investigate the effect of statin use on survival in patients with metastatic renal cell carcinoma (mRCC) treated in the modern therapy era.Patients and methodsWe conducted a pooled analysis of mRCC patients treated on phase II and III clinical trials. Statistical analyses were performed using Cox regression and the Kaplan–Meier method.ResultsWe identified 4736 patients treated with sunitinib (n = 1059), sorafenib (n = 772), axitinib (n = 896), temsirolimus (n = 457), temsirolimus + interferon (IFN)-α (n = 208), bevacizumab + temsirolimus (n = 393), bevacizumab + IFN-α (n = 391) or IFN-α (n = 560), of whom 511 were statin users. Overall, statin users demonstrated an improved overall survival (OS) compared to non-users (25.6 versus 18.9 months, adjusted hazard ratio [aHR] 0.801, 95% confidence interval [CI] 0.659–0.972, p = 0.025). When stratified by therapy type, a benefit in OS was demonstrated in statin users compared to non-users in individuals receiving therapy targeting vascular endothelial growth factor (28.4 versus 22.2 months, aHR 0.749, 95% CI 0.584–0.961, p = 0.023) or mammalian target of rapamycin (18.6 versus 14.0 months, aHR 0.657, 95% CI 0.445–0.972, p = 0.035) but not in those receiving IFN-α (15.6 versus 14.8 months, aHR 1.292, 95% CI 0.703–2.275, p = 0.410). Adverse events were similar between users and non-users.ConclusionsWe demonstrate that statin use may be associated with improved survival in patients with mRCC treated in the targeted therapy era. Statins could represent an adjunct therapy for patients with mRCC; however, this is hypothesis generating and requires prospective evaluation.     

Improved overall survival after implementation of targeted therapy for patients with metastatic renal cell carcinoma: Results from the Danish Renal Cancer Group (DARENCA) study-2

AimTo evaluate the implementation of targeted therapy on overall survival (OS) in a complete national cohort of patients with metastatic renal cell carcinoma (mRCC).MethodsAll Danish patients with mRCC referred for first line treatment with immunotherapy, TKIs or mTOR-inhibitors between 2006 and 2010 were included. Baseline and outcome data were collected retrospectively. Prognostics factors were identified using log-rank tests and Cox proportional hazard model. Differences in distributions were tested with the Chi-square test.Results1049 patients were referred; 744 patients received first line treatment. From 2006 to 2010 we observed a significant increase in the number of referred patients; a significant increase in treated patients (64% versus 75%, P = 0.0188); a significant increase in first line targeted therapy (22% versus 75%, P < 0.0001); a significant increase in second line treatment (20% versus 40%, P = 0.0104), a significant increased median OS (11.5 versus 17.2 months, P = 0.0435) whereas survival for untreated patients remained unchanged. Multivariate analysis validated known prognostic factors. Moreover, treatment start years 2008 (HR 0.74, 95% CI, 0.55–0.99; P = 0.0415), 2009 (HR 0.72, 95% CI, 0.54–0.96; P = 0.0277) and 2010 (HR 0.63, 95% CI, 0.47–0.86; P = 0.0035) compared to 2006, and more than two treatment lines received for patients with performance status 0–1 (HR 0.76, 95% CI, 0.58–0.99; P = 0.0397) and performance status 2–3 (HR 0.19, 95% CI, 0.06–0.60; P = 0.0051) were significantly associated with longer OS.ConclusionThis retrospective study documents that the implementation of targeted therapy has resulted in significantly improved treatment rates and overall survival in a complete national cohort of treated mRCC patients.     

Prognostic factors for survival in 1059 patients treated with sunitinib for metastatic renal cell carcinoma

Background:

Prognostic factors for progression-free survival (PFS), overall survival (OS), and long-term OS (⩾30 months) were investigated in sunitinib-treated patients with metastatic renal cell carcinoma (RCC).

Methods:

Data were pooled from 1059 patients in six trials. Baseline variables, including ethnicity, were analysed for prognostic significance by Cox proportional-hazards model.

Results:

Median PFS and OS were 9.7 and 23.4 months, respectively. Multivariate analysis of PFS and OS identified independent predictors, including ethnic origin, Eastern Cooperative Oncology Group performance status, time from diagnosis to treatment, prior cytokine use, haemoglobin, lactate dehydrogenase, corrected calcium, neutrophils, platelets, and bone metastases (OS only). Characteristics of long-term survivors (n=215, 20%) differed from those of non-long-term survivors; independent predictors of long-term OS included ethnic origin, bone metastases, and corrected calcium. There were no differences in PFS (10.5 vs 7.2 months; P=0.1006) or OS (23.8 vs 21.4 months; P=0.2135) in white vs Asian patients; however, there were significant differences in PFS (10.5 vs 5.7 months; P<0.001) and OS (23.8 vs 17.4 months; P=0.0319) in white vs non-white, non-Asian patients.

Conclusion:

These analyses identified risk factors to survival with sunitinib, including potential ethnic-based differences, and validated risk factors previously reported in advanced RCC.     

Progression-free survival and overall survival of patients with clear cell carcinoma of the ovary treated with paclitaxel-carboplatin or irinotecan-cisplatin: retrospective analysis

Background Irinotecan hydrochloride, a topoisomerase I inhibitor, has been preliminarily recognized as an effective agent against clear cell carcinoma of the ovary (CCC), but there are few clinical data. Our aim was to compare progression-free survival (PFS) between patients treated with irinotecan hydrochloride and cisplatin (CPT-P) and those with treated with paclitaxel and carboplatin (TC). Methods One hundred and seventeen patients at International Federation of Gynecology and Obstetrics (FIGO) stages Ic (ascites/malignant washing) – IV were identified by scanning the medical records of ten Japanese hospitals. After complete surgical staging procedures including lymphadenectomy, 35 patients received CPT-P and 82 patients received TC. The PFS and overall survival of the two groups were compared using the Kaplan-Meier method. Results There was no significant difference in median age, performance status, FIGO stage, rate of optimal cytoreduction, or follow-up period between the CPT-P and TC groups. Two-year and 5-year PFS was 48% and 40%, respectively, in the TC group and 55% and 55%, respectively, in the CPT-P group (P = 0.31). Multiple regression analysis revealed that only residual tumor was an independent prognostic factor for PFS (P < 0.01). Conclusion CPT-P showed a potential therapeutic effect, at least no less than that of TC therapy. Although there was no significant survival benefit in the present retrospective analysis, we recommend that the CPT-P regimen be evaluated in a larger, prospective, clinical trial.     

Visceral fat area as a new independent predictive factor of survival in patients with metastatic renal cell carcinoma treated with antiangiogenic agents

Purpose. A better identification of patients who are more likely to benefit from vascular endothelial growth factor-targeted therapy is warranted in metastatic renal cell carcinoma (mRCC). As adipose tissue releases angiogenic factors, we determined whether parameters such as visceral fat area (VFA) were associated with outcome in these patients. Experimental Design. In 113 patients with mRCC who received antiangiogenic agents (bevacizumab, sunitinib, or sorafenib) (n = 64) or cytokines (n = 49) as first-line treatment, we used computed tomography to measure VFA and subcutaneous fat area (SFA). We evaluated associations linking body mass index (BMI), SFA, and VFA to time to progression (TTP) and overall survival (OS). Results. High SFA and VFA values were significantly associated with shorter TTP and OS. By multivariate analysis, high VFA was independently associated with shorter TTP and OS. These results were internally validated using bootstrap analysis. By contrast, VFA was not associated with survival in the cytokine group. In the whole population, interaction between VFA and treatment group was significant for TTP and OS, thereby confirming the results. Conclusion. Our study provides the first evidence that high VFA could be a predictive biomarker from shorter survival in patients given first-line antiangiogenic agents for mRCC.     

A 2 weeks on and 1 week off schedule of sunitinib is associated with decreased toxicity in metastatic renal cell carcinoma

Treatment of metastatic renal cell carcinoma (mRCC) with sunitinib is often associated with toxicity necessitating dose reduction. Maintaining adequate dosing and drug levels are essential for optimising clinical efficacy. Standard sunitinib schedule is 4 weeks of treatment and 2 weeks of rest (schedule 4/2). Empirically, several mRCC patients at The Cleveland Clinic (CCF) have been changed from schedule 4/2 to 2 weeks of treatment/1 week off (schedule 2/1) after experiencing toxicity, in an attempt to maintain daily dosing.The medical records of 30 mRCC patients on sunitinib who were changed from schedule 4/2 to schedule 2/1 at CCF were retrospectively reviewed. Toxicity on each schedule was recorded during routine clinic visits and graded using Common Toxicity Criteria, version 4.0.97% of patients on schedule 4/2 had grade 3 or 4 toxicity that led to changing to schedule 2/1. There were no grade 4 toxicities on schedule 2/1, and 27% of patients experienced grade 3 toxicity (p = 0.0001). Two of the most common toxicities, fatigue and hand–foot syndrome (HFS), were significantly less frequent on schedule 2/1 than on schedule 4/2 (p = 0.0003; p = 0.0004, respectively). Median overall treatment duration on schedule 4/2 was 12.6 months (range 1.2 months–5.1 years) and median overall treatment duration on schedule 2/1 was 11.9 months (range 0.9+ to 73.3+ months).Treatment with sunitinib on schedule 2/1 is associated with significantly decreased toxicity in patients who experience grade 3 or greater toxicity on schedule 4/2, and can extend treatment duration considerably. Prospective clinical trials are required to define the optimal sunitinib schedule to balance efficacy and toxicity.     

舒尼替尼一线治疗转移性肾细胞癌的临床观察

目的:观察舒尼替尼一线治疗转移性肾细胞癌的有效性及安全性.方法:16例未经治疗的转移性肾细胞癌患者接受舒尼替尼治疗.14例患者口服舒尼替尼50 mg/d,服用4周休息2周,6周重复;2例患者口服37.5 mg/d,持续服用.结果:16例患者均可评价疗效和毒性.PR 5例,SD 9例,PD 2例;ORR为31.3％(5/16),DCR为87.5％(14/16).中位PFS和OS分别为10.5(95％CI:1.5～19.5)和17.5个月(95％CI:1.6～33.4).常见非血液学不良反应为手足综合征(12/16,75.0％)、乏力(11/16,68.8％)、口腔炎(8/16,50.0％)、高血压(8/16,50.0％)、纳差(9/16,56.3％)以及蛋白尿(6/16,37.5％);血液学主要不良反应为白细胞下降(10/16,62.5％)、血小板下降(9/16,56.3％).3～4级不良反应主要有口腔炎(3/16,18.8％)、高血压(2/16,l2.5％)、手足综合征(2/16,12.5％)、白细胞减少(2/16,12.5％)和血小板减少(2/16,12.5％).结论:舒尼替尼对未经治疗的中国人晚期肾细胞癌疗效确切,毒副反应可预见、可控制和可逆转,值得临床推荐使用.     

Targeted therapies for metastatic renal cell carcinoma: an overview of toxicity and dosing strategies

The targeted therapies sunitinib, sorafenib, temsirolimus, and bevacizumab (when used in combination with interferon-alpha2a) have dramatically improved outcomes for patients with advanced renal cell carcinoma (RCC). Clinical application of these novel agents outside the trial setting, however, may present some challenges for treating individual patients with unique needs. In some patients, dose modifications may be considered for potential drug interactions and for management of severe cases of hematologic or nonhematologic toxicities. The more common grade 3 or 4 side effects with sunitinib and sorafenib include hypertension, fatigue, hand-foot syndrome, elevated lipase, lymphopenia, and neutropenia. Congestive heart failure is a less common but serious side effect that warrants treatment discontinuation. Temsirolimus exhibits a different side-effect profile, with the more common grade 3 or 4 side effects being metabolic in nature (i.e., elevated triglycerides, elevated glucose, hypophosphatemia) as a result of its inhibitory effects on the mammalian target of rapamycin-regulated lipid and glucose pathways. Asthenia, rash, and dyspnea also occur in patients receiving temsirolimus. Virtually all of the side effects associated with these agents can be managed effectively in the majority of patients with medical treatment or supportive interventions. Recognition and prompt management of side effects are important to avoid unnecessary dose reductions that may result in suboptimal efficacy.     

Relationship between progression-free survival and overall survival in chronic lymphocytic leukemia: a literature-based analysis

Background

The endpoints of progression-free survival (pfs) and time-to-progression (ttp) are frequently used to evaluate the clinical benefit of anticancer drugs. However, the surrogacy of those endpoints for overall survival (os) is not validated in all cancer settings. In the present study, we used a trial-based approach to assess the relationship between median pfs or ttp and median os in chronic lymphocytic leukemia (cll).

Methods

The pico (population, interventions, comparators, outcomes) method was used to conduct a systematic review of the literature. The population consisted of patients with cll; the interventions and comparators were standard therapies for cll; and the outcomes were median pfs, ttp, and os. Two independent reviewers screened titles, abstracts, and full papers for eligibility and then extracted data from selected studies. Correlation coefficients were calculated to assess the relationship between median pfs or ttp and median os. Subgroup correlation analyses were also conducted according to the characteristics of the selected studies (such as line of treatment and type of treatment under investigation).

Results

Of the 1263 potentially relevant articles identified during the literature search, twenty-three were included. On average, median pfs or ttp was 16.0 months (standard deviation: 12.4 months) and median os was 43.5 months (standard deviation: 31.2 months). Results of the correlation analysis indicated that median pfs or ttp is highly correlated with median os (Spearman correlation coefficient: 0.813; p ≤ 0.001). A significant correlation between median pfs or ttp and median os was observed in second- and subsequent-line therapies, but not in the first-line setting.

Conclusions

Our study demonstrates a strong correlation between median pfs or ttp and median os in previously treated cll, which reinforce the hypothesis that pfs and ttp could be adequate surrogate endpoints for os in this cancer setting.     

Predictors,utilization patterns,and overall survival of patients undergoing metastasectomy for metastatic renal cell carcinoma in the era of targeted therapy

Introduction

Metastasectomy (MSX) is considered a treatment option in patients with metastatic renal cell carcinoma (mRCC) at diagnosis, but its role in the targeted therapy era is unclear. We sought to describe the utilization trends of MSX and survival outcomes in a large US cohort.