Comparative effectiveness of front-line agents in the treatment of metastatic clear cell renal cell carcinoma.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e15045-e15045
Author(s):  
Benjamin Haaland ◽  
Akhil Chopra ◽  
Gilberto de Lima Lopes
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Comparative Effectiveness ◽  
Clear Cell ◽  
Random Effect ◽  
P Value ◽  
Line Treatment ◽  
Front Line ◽  
Cell Renal Cell Carcinoma

e15045 Background: Based on improved clinical outcomes in randomized controlled clinical trials (RCT) the FDA has approved 4 drugs in the front line treatment of good to intermediate risk metastatic clear cell renal cell carcinoma (RCC). However, there is little if any comparative data to help choose the most effective drug among these agents. Methods: We performed an indirect comparative effectiveness analysis of the pivotal RCTs (Escudier JCO 2009 and 2010, Rini JCO 2010, Motzer JCO 2009, Sternberg JCO 2010, MRCRCC Lancet 1999, Steineck Acta Oncologica 1990, Pyrhonen JCO 1999, Kriegmair Urology 1995) evaluating outcomes with sunitinib (SU), sorafenib (SO), bevacizumab plus interferon alpha (B+I), pazopanib (P), interferon alone (I) and other controls. Progression-free-survival (PFS) was the main endpoint. Other endpoints included response rate (RR) and overall survival (OS). Estimates, confidence intervals, and p-values from analyses that are stratified by risk factors were used throughout if available. A linear mixed effects model with a random effect for each study and known error variances was fit by restricted maximum likelihood and used to obtain indirect estimates. Results: The indirect estimate of the hazard ratio (95% confidence interval; p-value) for PFS for SU vs. B+I is 0.813 (0.624-1.059; p=0.125); for B+I vs. SO is 0.753 (0.497-1.141; p=0.181); for P vs. B+I is 0.963 (0.612-1.518; p=0.874); for SU vs. SO is 0.613 (0.392-0.956; p=0.0311); for SU vs. P is 0.844 (0.521-1.366; p=0.49; for P vs. SO is 0.726 (0.407-1.295; p=0.278)(Figure 1). SU, P, B+I had better PFS than I alone and than other controls, while SO did not. SU had statistically significantly better RR when compared to P, SO and B+I with HR of 0.254, 0.215 and 0.419 (all p<0.05). OS data was not available to compare all agents and may be confounded by cross-over in the trials. Conclusions: Based on PFS, SU, B+I and P are adequate front line options in the treatment of advanced clear cell RCC. As SU had better RR it may be a preferred option for patients with symptoms or large disease burden. SO should not be considered an optimal front line treatment.

scholarly journals NOVEL PLASMA GLYCOPROTEIN BIOMARKERS PREDICT PROGRESSION-FREE SURVIVAL IN SURGICALLY RESECTED CLEAR CELL RENAL CELL CARCINOMA

2022 ◽  
Author(s):  
Daniel Serie ◽  
Amanda A Myers ◽  
Daniela A Haehn ◽  
Alexander Parker ◽  
Essa Bajalia ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Differential Expression ◽  
Renal Cell ◽  
Clear Cell ◽  
Progression Free Survival ◽  
P Value ◽  
Cell Renal Cell Carcinoma ◽  
Free Survival ◽  
Kaplan Meier

Introduction: Limited data exists on utilization of protein post-translational modifications as biomarkers for clear cell renal cell carcinoma (ccRCC). We employed high-throughput glycoproteomics to evaluate differential expression of glycoprotein-isoforms as novel markers for ccRCC progression-free survival (PFS). Methods: Plasma samples were obtained from 77 patients treated surgically for ccRCC. Glycoproteomic analyses were carried out after liquid chromatography tandem mass spectrometry. Age-adjusted Cox proportional hazard models were constructed to evaluate PFS. Optimized Harrells c-index was employed to dichotomize the collective for the construction of Kaplan-Meier curves. Results: The average length of follow-up was 3.4 (range: 0.04-9.83) years. Glycoproteomic analysis identified 39 glycopeptides and 14 non-glycosylated peptides that showed statistically significant (false discovery rate p ≤0.05) differential expression associated with PFS. Five of the glycosylated peptides conferred continuous hazard ratio of > 6 (range 6.3-11.6). These included prothrombin A2G2S glycan motif (HR=6.47, P=9.53E-05), immunoglobulin J chain FA2G2S2 motif (HR=10.69, P=0.001), clusterin A2G2 motif (HR=7.38, P=0.002), complement component C8A A2G2S2 motif (HR=11.59, P=0.002), and apolipoprotein M glycopeptide with non-fucosylated and non-sialylated hybrid-type glycan (HR=6.30, P=0.003). Kaplan-Meier curves based on dichotomous expression of these five glycopeptides resulted in hazard ratios of 3.9-10.7, all with p-value < 0.03. Kaplan-Meyer plot using the multivariable model comprising 3 of the markers yielded HR of 11.96 (p <0.0001). Conclusion: Differential glyco-isoform abundance of plasma proteins may be a useful source of biomarkers for the clinical course and prognosis of ccRCC.

scholarly journals Algorithms in the First‐Line Treatment of Metastatic Clear Cell Renal Cell Carcinoma—Analysis Using Diagnostic Nodes

2015 ◽  
Vol 20 (9) ◽  
pp. 1028-1035 ◽  
Author(s):  
Christian Rothermundt ◽  
Alexandra Bailey ◽  
Linda Cerbone ◽  
Tim Eisen ◽  
Bernard Escudier ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Line Treatment ◽  
First Line ◽  
Cell Renal Cell Carcinoma ◽  
Diagnostic Nodes ◽  
First Line Treatment

PDL-1 and PDL1 expressions in clear cell renal cell carcinoma (ccRCC) of metastatic patients with sunitinib first-line treatment.

2015 ◽  
Vol 33 (15_suppl) ◽  
pp. e14002-e14002 ◽  
Author(s):  
Angélique Brunot ◽  
Jean-Christophe Bernhard ◽  
Mokrane Yacoub ◽  
Julien Edeline ◽  
Gregory Verhoest ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Line Treatment ◽  
First Line ◽  
Cell Renal Cell Carcinoma ◽  
First Line Treatment

Real-world outcomes in patients with metastatic clear cell renal cell carcinoma receiving front-line axitinib plus pembrolizumab versus ipilimumab plus nivolumab.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 4551-4551
Author(s):  
Kevin Zarrabi ◽  
Elizabeth A. Handorf ◽  
Benjamin Miron ◽  
Matthew R. Zibelman ◽  
Fern Anari ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Real World ◽  
Renal Cell ◽  
Clear Cell ◽  
Cox Proportional Hazards ◽  
Combination Regimen ◽  
Front Line ◽  
Cell Renal Cell Carcinoma ◽  
Treatment Groups

4551 Background: Front-line treatment for patients (pts) with metastatic clear cell renal cell carcinoma (mRCC) has undergone rapid advances in the last five years. This evolution has led to uncertainty about the optimal first line combination regimen. Herein, we compare real-world outcomes in pts treated with either axitinib/pembrolizumab (A/P) or ipilimumab/nivolumab (I/N) reported by International Metastatic RCC Database Consortium (IMDC) score. Methods: The nationwide Flatiron Health electronic health records-derived database was used to select pts diagnosed with mRCC and treated with front-line A/P or I/N from 2018-2020. The primary endpoints were overall-survival (OS) and real-world progression free survival (rwPFS). The survival analyses were adjusted using propensity score-based Inverse Probability of Treatment weighting, providing balance on age, gender, insurance, race, IMDC, practice type, and nephrectomy. Survival was assessed from beginning of therapy, and survival by treatment groups was compared using weighted and unweighted Kaplan-Meier curves with log-rank tests and weighted Cox proportional hazards regressions. Disease characteristics between the treatment groups were compared using chi-square and T-tests. Results: 821 pts received frontline A/P (n=259) or I/N (n= 562). Demographics and clinical parameters were similar between the two cohorts. Median age was 66 years, 73% were male, and 54.9% had a nephrectomy. 459 pts had all IMDC criteria factors available, 242 pts had missing factors but enough to define as intermediate/poor risk, 120 pts had unknown IMDC risk. Adjusted median OS was not statistically different: mOS for A/P was not reached (NR) while I/N was 22 mo (95% CI, 19.8-NR; p=0.40). Twelve-month survival was 68.5% for A/P treated pts and 65.8% for I/N treated pts (P=0.41). Twelve-month rwPFS was 41.4% for A/P treated pts and 39.7% for I/N treated pts (P=0.14). No statistical difference in survival was seen within IMDC risk strata (see table). Conclusions: In this retrospective, real-world study of pts treated with front-line A/P or I/N, 12-month survival was not statistically different irrespective of IMDC risk. Longer follow-up will be necessary to discern any significant differences.[Table: see text]

Improving Outcomes in Metastatic Clear Cell Renal Cell Carcinoma by Sequencing Therapy

2014 ◽  
pp. e228-e238 ◽  
Author(s):  
Manuela Schmidinger
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Drug Exposure ◽  
Clear Cell ◽  
Local Treatment ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Cell Renal Cell Carcinoma

Targeted agents have substantially improved outcomes in metastatic clear cell renal cell carcinoma. However, due to multiple mechanisms of evasive resistance, almost all patients progress at some point and may require subsequent therapies. Various agents have been explored after failure of first-line treatment in randomized clinical trials. However, so far few questions about the optimal sequence have been answered. Both everolimus and axitinib have been considered standard of care after failure of first-line VEGF-TKI; sorafenib has been proposed as an additional option. In clinical practice, several factors may influence the choice of subsequent treatment: these include considerations on appropriate drug exposure in first-line, gained insights on prognostic and predictive factors as well as mechanisms of resistance. Once the decision in second-line has been made and treatment has been initiated, treating physicians may already be challenged by the question of what to offer in third- and later lines. Treatment beyond second-line treatment isn't supported by strong evidence, and at this stage of disease, retrospective reports on rechallenge may help to guide decisions. In addition, local treatment approaches including metastasectomy and stereotactic radiosurgery may help to optimize outcomes in all treatment lines.

scholarly journals First-line treatment of metastatic clear cell renal cell carcinoma: a decision-making analysis among experts

ESMO Open ◽  
2021 ◽  
Vol 6 (1) ◽  
pp. 100030 ◽  
Author(s):  
S. Aeppli ◽  
M. Schmaus ◽  
T. Eisen ◽  
B. Escudier ◽  
V. Grünwald ◽  
...  
Keyword(s):  
Decision Making ◽  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Line Treatment ◽  
First Line ◽  
Cell Renal Cell Carcinoma ◽  
First Line Treatment

scholarly journals Emerging Therapies for Advanced Clear Cell Renal Cell Carcinoma

2020 ◽  
Vol 7 (4) ◽  
pp. 17-26
Author(s):  
Alexander T. Toth ◽  
Daniel Cho
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Checkpoint Inhibitors ◽  
Standard Of Care ◽  
Small Subset ◽  
Front Line ◽  
Cell Renal Cell Carcinoma ◽  
Clear Cell Rcc

Multiple combinational regimens have recently been approved and are now considered the standard of care for patients with advanced clear cell renal cell carcinoma (RCC). Several additional combinational regimens are deep in clinical assessment and are likely to soon join the crowded front-line therapeutic landscape. Most of these regimens are combinations of agents already approved as single-agents in RCC including tyrosine kinase inhibitors (TKI) and immune checkpoint inhibitors. While these new front-line regimens are associated with reliably high response rates and prolonged survival, complete and durable remissions remain limited to a small subset of patients and the vast majority of patients continue to require subsequent therapy. The need for the continued development of novel agents in RCC persists and efforts have focused on agents targeting the molecular biology of clear cell RCC and novel immunotherapies including cytokines. In this review, we discuss the progress in the development of these novel therapies in the context of the evolving standard of care for patients with advanced clear cell RCC.

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