Checkpoint inhibitors in metastatic renal cell carcinoma patients including elderly subgroups: Results from the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 4580-4580
Author(s):  
Steven Yip ◽  
Connor Wells ◽  
Raphael Brandao Moreira ◽  
Alex Wong ◽  
Sandy Srinivas ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Real World ◽  
Renal Cell ◽  
Cox Regression ◽  
Cell Cancer ◽  
Second Line ◽  
Cox Regression Analysis ◽  
Poor Risk

4580 Background: Immuno-oncology (IO) checkpoint inhibitor treatment outcomes are poorly characterized in the real world metastatic renal cell cancer (mRCC) patient population, including geriatric patients. Methods: Using the IMDC database, a retrospective analysis was performed on mRCC patients treated with IO, as listed below. Patients received one or more lines of IO therapy, with or without a targeted agent. Duration of treatment (DOT) and overall response rates (ORR) were calculated. Cox regression analysis was performed to examine the association between age as a continuous variable and DOT. Results: 312 mRCC patients treated with IO were included. In patients who were evaluable, ORR to IO therapy was 29% (32% first-, 22% second-, 33% third-, and 32% fourth-line treatment (Tx)). Patients treated with second-line IO therapy were divided into favorable, intermediate, and poor risk using IMDC criteria; the corresponding median DOT rates were not reached (NR), 8.6 mo, and 1.9 mo, respectively (p<0.0001). Based upon age, hazard ratios were calculated in the first- through fourth-line therapy setting, ranging from 1.03 to 0.97. Conclusions: The ORR to IO appears to remain consistent, regardless of line of therapy. In the second-line, IMDC criteria appear to appropriately stratify patients into favorable, intermediate, and poor risk groups for DOT. Premature OS data will be updated. In contrast to clinical trial data, longer DOT is observed in real world practice. Age may not be a factor influencing DOT. [Table: see text]

scholarly journals Real-world outcomes of nivolumab and cabozantinib in metastatic renal cell carcinoma: results from the International Metastatic Renal Cell Carcinoma Database Consortium

2019 ◽  
Vol 26 (2) ◽  
Author(s):  
I. Stukalin ◽  
J. C. Wells ◽  
J. Graham ◽  
T. Yuasa ◽  
B. Beuselinck ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Real World ◽  
Renal Cell ◽  
Cox Regression ◽  
Kinase Inhibitor ◽  
Second Line ◽  
Cox Regression Analysis ◽  
Significant Difference

Objectives In the present study, we explored the real-world efficacy of the immuno-oncology checkpoint inhibitor nivolumab and the tyrosine kinase inhibitor cabozantinib in the second-line setting.Methods Using the International Metastatic Renal Cell Carcinoma Database Consortium (imdc) dataset, a retrospective analysis of patients with metastatic renal cell carcinoma (mrcc) treated with nivolumab or cabozantinib in the second line after prior therapy targeted to the vascular endothelial growth factor receptor (vegfr) was performed. Baseline characteristics and imdc risk factors were collected. Overall survival (os) and time to treatment failure (ttf) were calculated using Kaplan–Meier curves. Overall response rates (orrs) were determined for each therapy. Multivariable Cox regression analysis was performed to determine survival differences between cabozantinib and nivolumab treatment.Results The analysis included 225 patients treated with nivolumab and 53 treated with cabozantinib. No significant difference in median os was observed: 22.10 months [95% confidence interval (ci): 17.18 months to not reached] with nivolumab and 23.70 months (95% ci: 15.52 months to not reached) with cabozantinib (p = 0.61). The ttf was also similar at 6.90 months (95% ci: 4.60 months to 9.20 months) with nivolumab and 7.39 months (95% ci: 5.52 months to 12.85 months) with cabozantinib (p = 0.20). The adjusted hazard ratio (hr) for nivolumab compared with cabozantinib was 1.30 (95% ci: 0.73 to 2.3), p = 0.38. When adjusted by imdc criteria and age, the hr was 1.32 (95% ci: 0.74 to 2.38), p = 0.35.Conclusions Real-world imdc data indicate comparable os and ttf for nivolumab and cabozantinib. Both agents are reasonable therapeutic options for patients progressing after initial first-line vegfr-targeted therapy.

Second-line VEGF TKI after IO combination therapy: Results from the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC).

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 684-684
Author(s):  
Igor Stukalin ◽  
Shaan Dudani ◽  
Connor Wells ◽  
Chun Loo Gan ◽  
Sumanta K. Pal ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Combination Therapy ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Cox Regression ◽  
Response Rates ◽  
Second Line ◽  
First Line ◽  
Cox Regression Analysis

684 Background: Immuno-Oncology (IO) combinations are standard of care first-line treatment for metastatic renal cell carcinoma (mRCC). Data on therapy with vascular endothelial growth factor (VEGF) tyrosine kinase inhibitors (TKI) post-progression on IO-combination therapy are limited. Methods: Using the IMDC, a retrospective analysis was done on mRCC patients treated with second-line VEGF TKIs after receiving IO combination therapy. Patients received first-line ipilimumab+nivolumab (IOIO) or anti-PD(L)1+anti-VEGF (IOVE). Baseline variables and second-line IMDC risk factors were collected. Overall response rates (ORR), time to treatment failure (TTF) and overall survival (OS) were determined. Multivariable Cox regression analysis was performed. Results: 142 patients were included. 75 patients received IOIO and 67 received IOVE pretreatment. The ORR of 2nd line therapy was 17/46 (37%) and 7/57 (12%) in the IOIO and IOVE pretreated groups, respectively (p<0.01). 2nd-line TTF was 5.4 months (95% CI 4.1-8.3) for the IOIO- and 4.6 months (95% CI 3.7-5.8) for the IOVE-pretreated group (p=0.37). 2nd-line median OS was 17.2 months (95% CI 10.8-35.1) and 11.8 months (95% CI 9.9-21.3) for the prior IOIO and IOVE groups, respectively (p=0.13). The hazard ratio adjusted by IMDC for IOVE vs IOIO pretreatment was 1.22 (95% CI 0.73-2.07, p=0.45) for 2nd line TTF and 1.43 (95% CI 0.74-2.8, p=0.29) for 2nd line OS. Conclusions: VEGF TKIs show activity after combination IO therapy. Response rates are higher in patients treated with VEGF TKIs after first-line IOIO compared to after IOVE. In patients with VEGF TKI after IOIO or IOVE, no difference in OS and TTF was observed.[Table: see text]

scholarly journals First-line sunitinib or pazopanib in metastatic renal cell carcinoma: The Canadian experience

2017 ◽  
Vol 11 (3-4) ◽  
pp. 112 ◽  
Author(s):  
Aly-Khan A. Lalani ◽  
Haocheng Li ◽  
Daniel Y.C. Heng ◽  
Lori Wood ◽  
Austin Kalirai ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Real World ◽  
Renal Cell ◽  
Cox Regression ◽  
Cancer Information ◽  
First Line ◽  
Individualized Dosing ◽  
Selection Factors

Introduction: Clinical trial data has shown pazopanib to be noninferior in overall survival (OS) compared to sunitinib as first-line treatment for metastatic renal cell carcinoma (mRCC). The purpose of this study was to evaluate outcomes and compare dose-modifying toxicities of mRCC patients treated with suntinib or pazopanib in the real-world setting.Methods: Data were collected on mRCC patients using the prospective Canadian Kidney Cancer Information System (CKCis) database from January 2011 to November 2015. Statistical analyses were performed using Cox regression adjusted for several risk factors and the Kaplan-Meier method.Results: We identified 670 patients treated with sunitinib (n=577) and pazopanib (n=93). There were no significant differences in International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk groups (p=0.807). Patients treated with sunitinib had improved OS compared with pazopanib (median 31.7 vs. 20.6 months, p=0.028; adjusted hazard ratio [aHR] 0.60; 95% confidence interval [CI] 0.38‒0.94). Time to treatment failure (TTF) was numerically, but not statistically, improved with sunitinib (medians 11.0 vs. 8.4 months, p=0.130; aHR 0.87; 95% CI 0.59‒1.28). Outcomes with individualized dosing on sunitinib were unavailable for this analysis. Patients treated with sunitinib had a higher incidence of mucositis, hand-foot syndrome, and gastroesophageal reflux disease; patients treated with pazopanib had a higher incidence of hepatotoxicity.Conclusions: In Canadian patients with mRCC, treatment with sunitinib appears to be associated with an improved OS compared to pazopanib in the first-line setting. Patient selection factors and the contemporary practice of individualized dosing with sunitinib may contribute to these real-world outcomes and warrant further investigation.

Real-Word Experience of Cabozantinib in Metastatic Renal Cell Carcinoma (mRCC): Results from the Canadian Kidney Cancer information system (CKCis)

Kidney Cancer ◽  
2021 ◽  
pp. 1-9
Author(s):  
Hanbo Zhang ◽  
Naveen S. Basappa ◽  
Sunita Ghosh ◽  
Isaiah Joy ◽  
Aly-Khan A. Lalani ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Information System ◽  
Cell Carcinoma ◽  
Kidney Cancer ◽  
Metastatic Renal Cell Carcinoma ◽  
Real World ◽  
Renal Cell ◽  
Multivariable Analysis ◽  
Cancer Information ◽  
Second Line

Background: Cabozantinib is an oral multitargeted tyrosine kinase inhibitor (TKI) that has demonstrated efficacy in metastatic renal-cell carcinoma (mRCC) randomized trials. Objective: To explore the real-world effectiveness of cabozantinib in pretreated patients with mRCC, including patients who progressed on immune-oncology checkpoint inhibitor (ICI) therapy. Methods: Using the Canadian Kidney Cancer information system (CKCis), patients with mRCC treated with cabozantinib monotherapy as second-line or later from January 1, 2011 to September 1, 2019 were identified. Patients were stratified based on line of cabozantinib received. We reported overall survival (OS), time to treatment failure (TTF) and disease control rate (DCR). Prognostic variables were analyzed using multivariable analysis. Results: 157 patients received cabozantinib (median TTF 8.0 months; median OS 15.8 months): 37 (24%) in the second line (median TTF 10.4 months; median OS 18.9 months) 66 (42%) in third line (median TTF 5.9 months; median OS 13.3 months) and 54 (34%) in either 4th or 5th line (median TTF 9.4 months; median OS 16.8 months). One hundred sixteen patients (74%) received cabozantinib after prior ICI therapy (median TTF of 7.6 months; median OS of 15.8 months). DCR in all patients was 63% with 46%, 65% and 72% in 2nd line, 3rd line and 4th/5th line patients respectively. DCR in patients who received cabozantinib after prior ICI therapy was 64%. Conclusions: Cabozantinib is effective in a real-world, unselected population of mRCC patients, including in those who have progressed on prior ICI therapy, and in those exposed to multiple lines of therapy.

scholarly journals Circulating Levels of the Interferon-γ-Regulated Chemokines CXCL10/CXCL11, IL-6 and HGF Predict Outcome in Metastatic Renal Cell Carcinoma Patients Treated with Antiangiogenic Therapy

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2849
Author(s):  
Emilio Esteban ◽  
Francisco Exposito ◽  
Guillermo Crespo ◽  
Julio Lambea ◽  
Alvaro Pinto ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Cox Regression ◽  
Antiangiogenic Therapy ◽  
Prognostic Index ◽  
Serum Levels ◽  
Cox Regression Analysis ◽  
Tumor Expression

Sunitinib and pazopanib are standard first-line treatments for patients with metastatic renal cell carcinoma (mRCC). Nonetheless, as the number of treatment options increases, there is a need to identify biomarkers that can predict drug efficacy and toxicity. In this prospective study we evaluated a set of biomarkers that had been previously identified within a secretory signature in mRCC patients. This set includes tumor expression of c-Met and serum levels of HGF, IL-6, IL-8, CXCL9, CXCL10 and CXCL11. Our cohort included 60 patients with mRCC from 10 different Spanish hospitals who received sunitinib (n = 51), pazopanib (n = 4) or both (n = 5). Levels of biomarkers were studied in relation to response rate, progression-free survival (PFS) and overall survival (OS). High tumor expression of c-Met and high basal serum levels of HGF, IL-6, CXCL11 and CXCL10 were significantly associated with reduced PFS and/or OS. In multivariable Cox regression analysis, CXCL11 was identified as an independent biomarker predictive of shorter PFS and OS, and HGF was an independent predictor of reduced PFS. Correlation analyses using our cohort of patients and patients from TCGA showed that HGF levels were significantly correlated with those of IL-6, CXCL11 and CXCL10. Bioinformatic protein–protein network analysis revealed a significant interaction between these proteins, all this suggesting a coordinated expression and secretion. We also developed a prognostic index that considers this group of biomarkers, where high values in mRCC patients can predict higher risk of relapse (HR 5.28 [2.32–12.0], p < 0.0001). In conclusion, high plasma HGF, CXCL11, CXCL10 and IL-6 levels are associated with worse outcome in mRCC patients treated with sunitinib or pazopanib. Our findings also suggest that these factors may constitute a secretory cluster that acts coordinately to promote tumor growth and resistance to antiangiogenic therapy.

Real world outcomes of nivolumab and cabozantinib in metastatic renal cell carcinoma: Results from the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC).

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 615-615 ◽  
Author(s):  
Igor Stukalin ◽  
J Connor Wells ◽  
Jeffrey Graham ◽  
Takeshi Yuasa ◽  
Benoit Beuselinck ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Real World ◽  
Renal Cell ◽  
Phase Iii ◽  
Second Line ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy

615 Background: The immuno-oncology (IO) checkpoint inhibitor nivolumab and the tyrosine kinase inhibitor (TKI) cabozantinib have both been shown in phase III clinical trials to be effective in metastatic renal cell carcinoma (mRCC) after progression on first-line therapy. We sought to explore the real-world efficacy of these therapies in second-line mRCC. Methods: Using the IMDC database, a retrospective analysis was performed on mRCC patients treated with second-line nivolumab or cabozantinib. Baseline characteristics and IMDC risk factors were collected. Overall survival (OS), time to treatment failure (TTF), and response rates were determined for each therapy. Multivariable Cox regression analysis was performed to determine survival differences. Results: 225 patients were treated with nivolumab and 53 with cabozantinib. There was no significant difference in OS identified, with a mOS for nivolumab of 22.1 months (95% CI 17.18 – NR) and 23.7 months (95% CI 15.52 vs. NR) for cabozantinib, p = 0.6053. The TTF was also similar, with 6.90 months (95% CI 4.60 – 9.20) for nivolumab versus 7.39 months (95% CI 5.52 – 12.85) for cabozantinib, p = 0.1983. The adjusted hazard ratio (HR) for nivolumab vs. cabozantinib was 1.297 (95% CI – 0.728 – 2.312), p = 0.3775. Conclusions: Nivolumab and cabozantinib appear to have similar efficacy in terms of OS and TTF in this real-world patient population, thus both novel agents are reasonable therapeutic options for patients progressing after initial first-line therapy. [Table: see text]

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