The evolution of debulking nephrectomy and patient characteristics in metastatic renal cell cancer patients enrolled into first-line tyrosine kinase inhibitors clinical trials.

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 513-513
Author(s):  
Avishay Sella ◽  
Kongming Wang ◽  
Tal Sella
Keyword(s):  
Clinical Trials ◽  
Tyrosine Kinase ◽  
Phase I ◽  
Renal Cell ◽  
Kinase Inhibitors ◽  
Cell Cancer ◽  
Phase Iii ◽  
Cytokine Therapy ◽  
First Line ◽  
Group 2

513 Background: The introduction of tyrosine kinase inhibitors (TKIs) revolutionized treatment of metastatic renal cell cancer (mRCC). The role of debulking nephrectomy (DN) still remains unresolved. We reviewed the rate of DN and characteristics of patients enrolled in prospective clinical trials with TKIs through and after 2007 (Motzer, N Engl J Med, 2007). Methods: PubMed, Cochrane library, ASCO and ESMO web sites were searched for phase I-III clinical trials with at least 15 patients of first line TKIs administered alone/combination for mRCC. Expanded access/randomized discontinuation trials were excluded. We used PRISMA guidelines for data collection. All trials included histology, DN, prior cytokine therapy and efficacy data. Trials missing either performance status (PS) or MSKCC criteria data were included. We reviewed 72 trials; 42 trials are included: Group 1: 22 (phase I/II-19, phase III-3) trials completed through 2007 with 2,355 patients, Group 2: 20 trials (phase I/II-17, phase III-3) completed after 2007 with 3,719 patients. Thirty trials with 1,055 patients, all phase I/II, were excluded. Group characteristics were compared using a Pearson Chi-square test at a 2-sided significance level of 0.05, median progression free survival (PFS) with available 95% CI were compared using weighted T-Test. Results: Group 2 had statistically significantly (p<0.001) less DN (85.7% vs 93.7%), less prior cytokine therapy (11.7% vs 46.8%), more poor prognosis (9.8% vs 4.0%), and intermediate prognosis characteristics (56.0% vs 51.9%), more PS 2 (2.8% vs 0.8%), and a similar rate of clear cell histology (97.9% vs 97.2%, p=0.097). Clinical objective response per intent to treat analysis was higher in Group 2 (28.6% vs 23.1%, p<0.001) with similar clinical benefit (73.2% vs 75.3%, p=0.074) and comparable PFS (median 9 vs 8.2 months, p = 0.2528). Conclusions: The use of debulking nephrectomy in patients participating in clinical trials has declined in the TKIs era. More patients with worse prognostic parameters participated in TKI trials after 2007. The reduction in prior cytokine therapy prevents estimation of these changes on TKI efficacy.

scholarly journals Transition to Targeted Therapies Improved the Prognosis and Increased the Utilization of Medical Treatments among Patients with Synchronous Metastatic Renal Cell Cancer

2021 ◽  
Vol 2021 ◽  
pp. 1-7
Author(s):  
Lauri Laru ◽  
Hanna Ronkainen ◽  
Markku H. Vaarala
Keyword(s):  
Drug Therapy ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Renal Cell Cancer ◽  
Targeted Therapies ◽  
Renal Cell ◽  
Kinase Inhibitors ◽  
Cell Cancer ◽  
First Line ◽  
Metastatic Renal Cell Cancer

Since the introduction of targeted therapies (TTs) for metastatic renal cell cancer (mRCC) in 2005, a limited amount of epidemiological data on efficacy of modern drug therapies for synchronous mRCC has been published. We present a comprehensive nationwide cohort including all cases of primarily metastasized renal cell cancer among adults diagnosed between 2005 and 2010, based on data from the Finnish Cancer Registry and patient records from treating hospitals. Applied treatment protocols and survival outcomes were analyzed. A total of 977 patients were included in the analysis; 499 patients were diagnosed between 2005 and 2007 and 478 patients were diagnosed between 2008 and 2010. The median overall survival (OS) was 8.80 months (95% confidence interval (CI): 7.60–10.02). The median OS of the patients diagnosed at the latter era was significantly better (11.1; 95% CI: 8.8–13.4 vs. 7.0; 95% CI: 5.7–8.3 months, p ≤ 0.001 ). A total number of 524 (53.8%) patients received drug therapy. Altogether, TTs including tyrosine kinase inhibitors, mammalian target of rapamycin inhibitors (mTORi), and vascular endothelial growth factor inhibitor covered 331 (63.2%) of first-line treatments, whereas interferon and its combinations with chemotherapy were used for 186 (35.5%) patients. The median OS rates for TT and interferon as first-line therapy groups were 19.9 (16.9–22.8) and 14.9 (12.3–17.4) months, respectively. The OS for patients who did not receive drug therapy after cytoreductive nephrectomy was dismal. We found that the OS estimate of mRCC patients in Finland has improved since the introduction of tyrosine kinase inhibitors. However, the prognosis remains poor for frail, elderly patients with an impaired performance status.

scholarly journals Emerging role of tyrosine kinase inhibitors in the treatment of advanced renal cell cancer: a review

2006 ◽  
Vol 17 (8) ◽  
pp. 1185-1196 ◽  
Author(s):  
P. Schöffski ◽  
H. Dumez ◽  
P. Clement ◽  
A. Hoeben ◽  
H. Prenen ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Renal Cell Cancer ◽  
Renal Cell ◽  
Kinase Inhibitors ◽  
Cell Cancer ◽  
Advanced Renal Cell Cancer

scholarly journals Evaluation of second line and subsequent targeted therapies in metastatic renal cell cancer (mRCC) patients treated with first line cediranib

2014 ◽  
Vol 8 (11-12) ◽  
pp. 398 ◽  
Author(s):  
Suzanne Richter ◽  
Jo-An Seah ◽  
Gregory R Pond ◽  
Hui K Gan ◽  
Mary J. Mackenzie ◽  
...  
Keyword(s):  
Renal Cell ◽  
Kinase Inhibitor ◽  
Cell Cancer ◽  
Phase Iii ◽  
Second Line ◽  
First Line ◽  
Second Line Therapy ◽  
Pivotal Phase ◽  
Line Therapy ◽  
To Receive

Introduction: Pivotal phase III trials have positioned angiogenesis inhibitors as first-line therapy for the management of most advanced or metastatic renal cell carcinomas (mRCC). Approaches to second-line therapy, however, remain more controversial with respect to drug selection and drug sequencing.Methods: In this study we evaluated mRCC patients who were initially treated on the first-line National Cancer Institute (NCI) trial with the highly potent vascular endothelial growth factor receptor tyrosine kinase inhibitor (TKI), cediranib, to determine the efficacy and tolerability of subsequent therapies.Results: Twenty-eight (65.1%) of the 43 patients enrolled on the first-line cediranib trial were known to receive second-line therapy, most commonly sunitinib (n = 21), with 4 (14%), 2 (7%) and 1 (3%) patients receiving temsirolimus, sorafenib, and interleukin, respectively. Of these, 14 (50%) went on to have 3 or more lines of therapy. The progression-free survival (PFS) proportion (PFS) at 1 year from starting second line was 30% (14.5%–47.9%). Longer duration of first-line cediranib treatment was modestly associated with longer duration of second-line treatment (Spearman rho 0.26). Patients who discontinued cediranib for toxicity were less likely to receive second-line sunitinib.Conclusion: In this real world evaluation, sequential use of TKIs for the management of mRCC was common. PFS with sequential TKIs was similar to observed and published results for any second-line therapy. Prior toxicity affected treatment patterns and the frequent use of at least 3 lines of therapy underscores the need for prospective sequencing trials in this disease.

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