Tyrosine kinase inhibitors and development of brain metastasis in metastatic renal cell carcinoma: A retrospective review.

2011 ◽  
Vol 29 (7_suppl) ◽  
pp. 340-340
Author(s):  
J. Verma ◽  
E. Jonasch ◽  
P. Allen ◽  
N. M. Tannir ◽  
A. Mahajan
Keyword(s):  
Renal Cell Carcinoma ◽  
Multivariate Analysis ◽  
Brain Metastasis ◽  
Cell Carcinoma ◽  
Lung Metastasis ◽  
Renal Cell ◽  
Kinase Inhibitors ◽  
Risk Category ◽  
Tki Treatment ◽  
Initial Staging

340 Background: Tyrosine kinase inhibitors (TKIs) have been shown to improve overall survival (OS) in metastatic renal cell carcinoma (mRCC) but their effect on brain metastasis (BM) development is unclear. The purpose of our study is to evaluate the impact of TKIs on incidence of BM and OS in patients with mRCC. Methods: Searched the M. D. Anderson Cancer Center (MDACC) tumor registry for patients who presented with mRCC in 2002-2003 and 2006-2007 with no BM at initial staging. The following items were retrospectively collected: age, sex, Fuhrman grade, sites of disease, nephrectomy, systemic therapy including TKIs (sorafenib or sunitinib), MSKCC risk category, BM treatment, and vital status. Interaction between OS and incidence of BM and these variables was estimated using the Cox proportional hazards model. OS and incidence of BM were estimated using the Kaplan-Meier (K-M) method. Results: 338 patients were identified; 154 (46%) were treated with a TKI prior to BM, and 184 (54%) were not. There were no significant differences in age, histology, involved sites of disease other than lung, nephrectomy, or MSKCC risk category between the groups. A higher proportion of the nonTKI group received other systemic agents and had lung metastasis at initial staging (p=0.03). Median OS was longer in the TKI-treated group (25 months versus 12.1 months, p<0.0001). In Cox multivariate analysis, TKI treatment (HR=0.53, 95% CI 0.38-0.74, p<0.001) was associated with improved OS and lung/mediastinal involvement and ECOG performance status > 2 (HR 1.87, 95% CI 1.28-2.71, p=0.001) were associated with poor OS. Median OS after BM was not significantly different between TKI treated and untreated groups. 44 patients (13%) developed a BM, including 29 (15.8%) of the nonTKI group and 15 (9.7%) of the TKI group. In K-M analysis, the 5-year incidence of BM was 40% versus 17% respectively (logrank p<0.001). In Cox multivariate analysis, TKI treatment was associated with lower incidence of BM (HR=0.39, 95% CI 0.21-0.73, p=0.003). Lung metastasis increased the risk of BM (HR=9.61, 95% CI 2.97-31.1, p<0.001). Conclusions: Treatment with TKI agents reduces the incidence of BM in mRCC. Lung metastasis is a risk factor for BM development. No significant financial relationships to disclose.

scholarly journals Impact of tyrosine kinase inhibitors on the incidence of brain metastasis in metastatic renal cell carcinoma

Cancer ◽  
2011 ◽  
Vol 117 (21) ◽  
pp. 4958-4965 ◽  
Author(s):  
Jonathan Verma ◽  
Eric Jonasch ◽  
Pamela Allen ◽  
Nizar Tannir ◽  
Anita Mahajan
Keyword(s):  
Renal Cell Carcinoma ◽  
Brain Metastasis ◽  
Tyrosine Kinase ◽  
Cell Carcinoma ◽  
Tyrosine Kinase Inhibitors ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Kinase Inhibitors

scholarly journals Complete Remission With Tyrosine Kinase Inhibitors in Renal Cell Carcinoma

2012 ◽  
Vol 30 (5) ◽  
pp. 482-487 ◽  
Author(s):  
Laurence Albiges ◽  
Stéphane Oudard ◽  
Sylvie Negrier ◽  
Armelle Caty ◽  
Gwenaëlle Gravis ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Complete Remission ◽  
Tyrosine Kinase ◽  
Cell Carcinoma ◽  
Tyrosine Kinase Inhibitors ◽  
Renal Cell ◽  
Kinase Inhibitors ◽  
Local Treatment ◽  
Tki Treatment

Purpose Complete remission (CR) is uncommon during treatment for metastatic renal cell carcinoma (mRCC) with tyrosine kinase inhibitors (TKIs), but it may occur in some patients. It remains a matter of debate whether therapy should be continued after CR. Methods A multicenter, retrospective analysis of a series of patients with mRCC who obtained CR during treatment with TKIs (sunitinib or sorafenib), either alone or with local treatment (surgery, radiotherapy, or radiofrequency ablation), was performed. Results CR was identified in 64 patients; 36 patients had received TKI treatment alone and 28 had also received local treatment. Most patients had clear cell histology (60 of 64 patients), and all had undergone previous nephrectomy. The majority of patients were favorable or intermediate risk; however, three patients were poor risk. Most patients developed CR during sunitinib treatment (59 of 64 patients). Among the 36 patients who achieved CR with TKI alone, eight continued TKI treatment after CR, whereas 28 stopped treatment. Seventeen patients who stopped treatment (61%) are still in CR, with a median follow-up of 255 days. Among the 28 patients in CR after TKI plus local treatment, 25 patients stopped treatment, and 12 of these patients (48%) are still in CR, with a median follow-up of 322 days. Conclusion CR can occur after TKI treatment alone or when combined with local treatment. CR was observed at every metastatic site and in every prognostic group.

Outcomes of immunotherapy (ICI) alone vs tyrosine kinase inhibitors (TKI) alone versus ICI and TKI combined in renal cell carcinoma brain metastasis.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 2030-2030
Author(s):  
Patrick Joseph O'Shea ◽  
Vineeth Tatineni ◽  
Yasmeen Rauf ◽  
Xuefei Jia ◽  
Erin Sennett Murphy ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Brain Metastasis ◽  
Cell Carcinoma ◽  
Combination Treatment ◽  
Renal Cell ◽  
Kinase Inhibitors ◽  
Age At Diagnosis ◽  
Line Treatment ◽  
First Line ◽  
First Line Treatment

2030 Background: Renal cancer is the fourth most common cause of metastatic tumors to the brain. Tyrosine kinase inhibitors (TKIs) targeting VEGFR and other receptors, such as sunitinib, pazopanib, etc., have been used as first line for renal cell carcinoma brain metastasis (RCCBM). Immune Checkpoint Inhibitors (ICIs) targeting PD-L1 and CTLA-4 interactions, such as nivolumab and ipilimumab respectively, have also been used as first line treatment for RCCBM. However, the efficacy of TKIs alone, ICIs alone, or TKIs and ICIs combined as first line treatment has emerged as a topic of interest. Methods: Patients with RCCBM treated with either TKIs, ICIs, or both at our tertiary care center from 2010-2019 were evaluated. Overall Survival (OS) was measured from initiation of either TKI or ICI therapy to date of death or last follow up. The Cox proportional hazard model was used to determine differences in OS. Results: 218 patients with RCCBM were included. Of these, 32 were treated with ICIs alone, 112 were treated with TKIs alone, and 76 were treated with a combination of ICIs and TKIs. For ICI treatment alone the median age at diagnosis was 61 years (Interquartile range (IQR) 38-82), 72% of the patients were male, and 97% were white. For TKI treatment alone the median age at diagnosis was 58 years (IQR 37-82), 70% of the patients were male, and 92% were white. For the combination cohort the median age at diagnosis was 63 years (IQR 45-79), 69% of the patients were male, and 97% were white. OS for patients receiving ICI, TKI, and combination treatment had a median of 69.1, 42.7, and 126.0 months and a 2-year rate of 77%, 69%, and 93%, respectively. With ICI treatment as a reference, TKI treated patients had an OS hazard ratio of 1.32 (95% CI = 0.78 - 2.21, p = 0.30) and ICI/TKI combination had an OS hazard ratio of 0.52 (95% CI = 0.30 - 0.92, p = 0.024). Conclusions: A combination treatment of ICIs and TKIs was associated with an increase in OS when compared to treatment with either TKIs or ICIs alone in patients with RCCBM. These results should be interpreted cautiously due to treatment selection bias. Further studies need to be done to control for other patient variables such as performance status, number of intracranial lesions, and extra-cranial metastasis.[Table: see text]

scholarly journals Impact of COVID-19 pandemic on treatment patterns in metastatic clear cell renal cell carcinoma

ESMO Open ◽  
2020 ◽  
Vol 5 (Suppl 3) ◽  
pp. e000852 ◽  
Author(s):  
Stefanie Aeppli ◽  
Eric Innocents Eboulet ◽  
Tim Eisen ◽  
Bernard Escudier ◽  
Stefanie Fischer ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Online Survey ◽  
Kinase Inhibitors ◽  
Clear Cell ◽  
Treatment Decision ◽  
Risk Category ◽  
Cell Renal Cell Carcinoma ◽  
Risk Patients

BackgroundThe coronavirus pandemic has provoked discussions among healthcare providers how to manage cancer patients when faced with the threat of severe acute respiratory syndrome related coronavirus 2 (SARS-CoV-2) infection. Immune checkpoint inhibitor (ICI) containing regimens are standard of care in the majority of metastatic clear cell renal cell carcinoma (mccRCC) patients. It remains unclear whether therapies should be modified in response to the COVID-19 pandemic.MethodsWe performed an online survey among physicians involved in the treatment of mccRCC, and 41 experts responded. Questions focused on criteria relevant for treatment decision outside the pandemic and the modifications of systemic therapy during COVID-19.FindingsFor the majority of experts (73%), the combination of International metastatic renal cell carcinoma Database Consortium (IMDC) risk category and patient fitness are two important factors for decision-making. The main treatment choice in fit, favourable risk patients outside the pandemic is pembrolizumab/axitinib for 53%, avelumab/axitinib, sunitinib or pazopanib for 13% of experts each. During the pandemic, ICI-containing regimens are chosen less often in favour of a tyrosine kinase inhibitors (TKI) monotherapy, mainly sunitinib or pazopanib (35%).In fit, intermediate/poor-risk patients outside the pandemic, over 80% of experts choose ipilimumab/nivolumab, in contrast to only 41% of physicians during COVID-19, instead more TKI monotherapies are given. In patients responding to established therapies with ICI/ICI or ICI/TKI combinations, most participants modify treatment regimen by extending cycle length, holding one ICI or even both.ConclusionmccRCC treatment modifications in light of the coronavirus pandemic are variable, with a shift from ICI/ICI to ICI/TKI or TKI monotherapy.

scholarly journals miR-9-5p in Nephrectomy Specimens is a Potential Predictor of Primary Resistance to First-Line Treatment with Tyrosine Kinase Inhibitors in Patients with Metastatic Renal Cell Carcinoma

Cancers ◽  
2018 ◽  
Vol 10 (9) ◽  
pp. 321 ◽  
Author(s):  
Bernhard Ralla ◽  
Jonas Busch ◽  
Anne Flörcken ◽  
Jörg Westermann ◽  
Zhongwei Zhao ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Tyrosine Kinase ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Kinase Inhibitors ◽  
Line Treatment ◽  
First Line ◽  
Primary Resistance ◽  
Tki Treatment ◽  
First Line Treatment

Approximately 20–30% of patients with metastatic renal cell carcinoma (mRCC) in first-line treatment with tyrosine kinase inhibitors (TKIs) do not respond due to primary resistance to this drug. At present, suitable robust biomarkers for prediction of a response are not available. Therefore, the aim of this study was to evaluate a panel of microRNAs (miRNAs) in nephrectomy specimens for use as predictive biomarkers for TKI resistance. Archived formalin-fixed, paraffin embedded nephrectomy samples from 60 mRCC patients treated with first-line TKIs (sunitinib, n = 51; pazopanib, n = 6; sorafenib, n = 3) were categorized into responders and non-responders. Using the standard Response Evaluation Criteria in Solid Tumors, patients with progressive disease within 3 months after the start of treatment with TKI were considered as non-responders and those patients with stable disease and complete or partial response under the TKI treatment for at least 6 months as responders. Based on a miRNA microarray expression profile in the two stratified groups of patients, seven differentially expressed miRNAs were validated using droplet digital reverse-transcription quantitative real-time polymerase chain reaction (RT-qPCR) assays in the two groups. Receiver operating characteristic curve analysis and binary logistic regression of response prediction were performed. MiR-9-5p and miR-489-3p were able to discriminate between the two groups. MiR-9-5p, as the most significant miRNA, improved the correct prediction of primary resistance against TKIs in comparison to that of conventional clinicopathological variables. The results of the decision curve analyses, Kaplan-Meier analyses and Cox regression analyses confirmed the potential of miR-9-5p in the prediction of response to TKIs and the prediction of progression-free survival after the initiation of TKI treatment.

1011: Suppression of Renal Cell Carcinoma Lung Metastasis by Adeno-Associated Virus (AAV) Mediated Gene Transfer of a Soluble Receptor of VEGF

2004 ◽  
Vol 171 (4S) ◽  
pp. 267-267
Author(s):  
Ichiro Yoshimura ◽  
Yasunori Mizuguchi ◽  
Akira Miyajima ◽  
Tomohiko Asano ◽  
Hiroaki Mizukami ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Gene Transfer ◽  
Cell Carcinoma ◽  
Lung Metastasis ◽  
Renal Cell ◽  
Soluble Receptor ◽  
Adeno Associated Virus

Comparing the Responses of Osseous Versus Soft-Tissue Metastases of Renal Cell Carcinoma to Receptor Tyrosine Kinase Inhibitors and Immunotherapy

Kidney Cancer ◽  
2020 ◽  
Vol 4 (3) ◽  
pp. 151-158
Author(s):  
Katherine Yuxi Tai ◽  
Jad M. El Abiad ◽  
Carol D. Morris ◽  
Mark Christopher Markowski ◽  
Adam S. Levin
Keyword(s):  
Renal Cell Carcinoma ◽  
Soft Tissue ◽  
Cell Carcinoma ◽  
Receptor Tyrosine Kinase ◽  
Renal Cell ◽  
Kinase Inhibitors ◽  
Tissue Response ◽  
Bone Response ◽  
Soft Tissue Response ◽  
Receptor Tyrosine Kinase Inhibitors

BACKGROUND: Checkpoint inhibitors and receptor tyrosine kinase inhibitors (RTKIs) have changed the standard of care for metastatic renal cell carcinoma (mRCC). Anecdotal evidence suggests these therapies may be less effective for treating bone than soft-tissue metastases. PURPOSE: We performed a retrospective review evaluating the relative clinical responses in soft-tissue and bone metastases in patients undergoing therapy using RTKIs and anti-programmed death-1 (PD-1) agents for mRCC. METHODS: Of the 2,212 patients in our institutional cancer registry with renal cell carcinoma (1997–2017), 68 (82 disease courses) were identified with measurable bone and soft-tissue metastases treated with RTKIs and/or PD-1s. Extent of metastasis was quantified at the time of therapy initiation (baseline) and at 3 months, 6 months, and 1 year. Changes in disease status were categorized as complete response, partial response, stable, mixed, or progression of disease according to RECIST v1.1 and MD Anderson criteria. These categories were further organized into “response to treatment” or “evidence of progression” to generate a generalized linear effects model with soft-tissue response as the independent variable and bone response as the dependent variable. Alpha = 0.05. RESULTS: Soft-tissue response correlated with bone response at 3 months (76 disease courses, p = 0.005) and 6 months (48 disease courses, p = 0.017). Of the patients with controlled soft-tissue disease, only 14 (19%) and 15 (32%) had progression in bone at 3 and 6 months, respectively. CONCLUSION: Contrary to anecdotal reports, osseous metastases do not appear to respond worse than soft-tissue metastases to treatment with these agents.

Adjuvant Therapy in Renal Cell Carcinoma: Current Stance and Future Directions

Kidney Cancer ◽  
2021 ◽  
pp. 1-12
Author(s):  
Austin G. Kazarian ◽  
Neal S. Chawla ◽  
Ramya Muddasani ◽  
Sumanta K. Pal
Keyword(s):  
Renal Cell Carcinoma ◽  
Adjuvant Therapy ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Kinase Inhibitors ◽  
Checkpoint Inhibitors ◽  
Unmet Need ◽  
Disease Free Survival ◽  
Adjuvant Setting ◽  
Metastatic Setting

In recent years, incredible progress has been made in the treatment of metastatic renal cell carcinoma, with a paradigm shift from the use of cytokines to tyrosine kinase inhibitors, and more recently, immune checkpoint inhibitors (ICIs). Despite advances in the metastatic setting, effective therapies in the adjuvant setting are a largely unmet need. Currently, sunitinib (Sutent, Pfizer) is the only therapy for the adjuvant treatment of RCC included in the National Comprehensive Cancer Network guidelines, which was approved by the FDA based on the improvement in disease-free survival (DFS) seen in the S-TRAC trial. However, improvement in DFS has not translated into an overall survival (OS) benefit for patients at high-risk of relapse post-nephrectomy, illustrating the need for more effective therapies. This manuscript will highlight attributes of both historical and current drug trials and their implications on the landscape of adjuvant therapy. Additionally, we will outline strategies for selecting patients in whom treatment would be most beneficial, as optimal patient selection is a crucial step towards improving outcomes in the adjuvant setting. This is especially critical, given the financial cost and pharmacological toxicity of therapeutic agents. Furthermore, we will review the design of clinical trials including the value of utilizing OS as an endpoint over DFS. Finally, we will discuss how the incorporation of genomic data into predictive models, the use of more sensitive imaging modalities for more accurate staging, and more extensive surgical intervention involving lymph node dissection, may impact outcomes.

scholarly journals Multidiscipline Immunotherapy-Based Rational Combinations for Robust and Durable Efficacy in Brain Metastases from Renal Cell Carcinoma

2021 ◽  
Vol 22 (12) ◽  
pp. 6290
Author(s):  
Hye-Won Lee
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Kinase Inhibitors ◽  
Checkpoint Inhibitors ◽  
Imaging Techniques ◽  
Predictive Biomarkers ◽  
Effective Control ◽  
Extrinsic Factors ◽  
Medical Needs

Advanced imaging techniques for diagnosis have increased awareness on the benefits of brain screening, facilitated effective control of extracranial disease, and prolonged life expectancy of metastatic renal cell carcinoma (mRCC) patients. Brain metastasis (BM) in patients with mRCC (RCC-BM) is associated with grave prognoses, a high degree of morbidity, dedicated assessment, and unresponsiveness to conventional systemic therapeutics. The therapeutic landscape of RCC-BM is rapidly changing; however, survival outcomes remain poor despite standard surgery and radiation, highlighting the unmet medical needs and the requisite for advancement in systemic therapies. Immune checkpoint inhibitors (ICIs) are one of the most promising strategies to treat RCC-BM. Understanding the role of brain-specific tumor immune microenvironment (TIME) is important for developing rationale-driven ICI-based combination strategies that circumvent tumor intrinsic and extrinsic factors and complex positive feedback loops associated with resistance to ICIs in RCC-BM via combination with ICIs involving other immunological pathways, anti-antiangiogenic multiple tyrosine kinase inhibitors, and radiotherapy; therefore, novel combination approaches are being developed for synergistic potential against RCC-BM; however, further prospective investigations with longer follow-up periods are required to improve the efficacy and safety of combination treatments and to elucidate dynamic predictive biomarkers depending on the interactions in the brain TIME.

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