Clinicopathologic features of Xp11.2 translocation renal cell carcinoma and its response to target therapy.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16559-e16559
Author(s):  
Xieqiao Yan ◽  
Zhihong Chi ◽  
Lu Si ◽  
Chuanliang Cui ◽  
Yan Kong ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Systemic Therapy ◽  
Renal Cell ◽  
Kinase Inhibitor ◽  
Target Therapy ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Line Therapy ◽  
Xp11.2 Translocation

e16559 Background: Xp11.2 translocation renal cell carcinoma (RCC) is a unique RCC subtype with high malignant potential and poor prognosis, its natural course and response to systemic therapy are not fully understood. We analyzed the clinic features of this distinct entity and the benefit of systemic therapy in these patients. Methods: Between May 2006 and December 2019, 1113 consecutive patients diagnosed with RCC from Peking university cancer hospital (Beijing, China) were reviewed, data of the clinical characteristics and outcome of patients with metastatic Xp11.2 RCC were retrospectively collected. Tumor response to systemic therapy was evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) criteria. The Kaplan-Meier method was used to estimate progression-free survival (PFS) and overall survival (OS) distributions. Results: Metastatic Xp11.2 translocation RCC was found in 41 cases. The median PFS and Median OS was 6.3 months (4.4 - 8.8) and 17.3 months (12.4 - 21.8) for the whole cohort, respectively. First-line treatment mainly included sunitinib (n = 12), sorafenib (n = 13), axitinib (n = 6), and pazopanib (n = 4), and the median PFS of these regimens was 5.4 months, 5.1 months, 9.4 months, 8.3 months, respectively. Twenty-three patients received subsequent therapies, the median PFS and the median OS was 4.3 months and 12 months for the second-line therapy(n = 21), 4.3 months and 14.1 months for the third-line therapy(n = 11), 2.4 months and 9.6 months for the fourth-line therapy(n = 6). Conclusions: Metastatic Xp11.2 translocation RCC is an aggressive disease. Vascular endothelial growth factor receptor - tyrosine kinase inhibitor (VEGFR-TKI) agents appeared to demonstrate some efficacy, the combination of VEGFR-TKI and immune checkpoint inhibitor (ICI) might be a useful tool for the treatment of metastatic Xp11.2 translocation RCC.

scholarly journals Effect of third- and fourth-line systemic therapies for metastatic renal cell carcinoma

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Sei Naito ◽  
Osamu Ichiyanagi ◽  
Tomoyuki Kato ◽  
Hidenori Kanno ◽  
Takafumi Narisawa ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Systemic Therapy ◽  
Renal Cell ◽  
Objective Response ◽  
Progression Free Survival ◽  
University Hospital ◽  
Line Therapy ◽  
Third Line

Abstract Data on the outcomes of third- or fourth-line therapy for metastatic renal cell carcinoma (mRCC) are limited. The aim of our study was to evaluate the efficacy of therapy beyond the second line. We retrospectively analysed data of mRCC patients who underwent systemic therapy at Yamagata University Hospital. The best objective response (BOR), response rate (RR), and progression-free survival (PFS) were assessed for each line of treatment. To investigate the correlation between overall survival (OS) and the number of treatment lines during a patient’s lifetime, the median OS was assessed using univariate and multivariate analyses. In the first-, second-, and third-line therapies, approximately 20% of patients had long PFS of >15 months. In targeted treatments beyond the third line, only one treatment suppressed disease progression for >10 months. Among patients who died during the follow-up period, those treated with triple and quadruple lines had similar OS (42.5 months vs. 48.4 months, respectively). Multivariate analysis showed that patients with triple or more lines of therapy had better OS; however, quadruple or more lines of therapy was not an independent prognostic factor. We concluded that third-line systemic therapy could improve OS; however, fourth-line therapy could not.

scholarly journals Long-term progression-free survival of patients with metastatic melanoma or renal cell carcinoma following high-dose interleukin-2

2021 ◽  
Vol 69 (4) ◽  
pp. 888-892
Author(s):  
Joseph I Clark ◽  
Brendan Curti ◽  
Elizabeth J Davis ◽  
Howard Kaufman ◽  
Asim Amin ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Melanoma ◽  
Systemic Therapy ◽  
Renal Cell ◽  
Interleukin 2 ◽  
Progression Free Survival ◽  
High Dose ◽  
Free Survival

High-dose interleukin-2 (HD IL-2) was approved in the 1990s after demonstrating durable complete responses (CRs) in some patients with metastatic melanoma (mM) and metastatic renal cell carcinoma (mRCC). Patients who achieve this level of disease control have also demonstrated improved survival compared with patients who progress, but limited data are available describing the long-term course. The aim of this study was to better characterize long-term survival following successful HD IL-2 treatment in patients with no subsequent systemic therapy. Eleven HD IL-2 treatment centers identified patients with survival ≥5 years after HD IL-2, with no subsequent systemic therapy. Survival was evaluated from the date of IL-2 treatment to June 2017. Treatment courses consisted of 2 1-week cycles of HD IL-2. Patients were treated with HD IL-2 alone, or HD IL-2 followed by local therapy to achieve maximal response. 100 patients are reported: 54 patients with mM and 46 patients with mRCC. Progression-free survival (PFS) after HD IL-2 ranges from 5+ years to 30+ years, with a median follow-up of 10+ years. 27 mRCC and 32 mM are alive ≥10 years after IL-2. Thus, a small subset of patients with mM and mRCC achieve long-term PFS (≥5 years) after treatment with HD IL-2 as their only systemic therapy. The ability of HD IL-2 therapy to induce prolonged PFS should be a major consideration in studies of new immunotherapy combinations for mM and mRCC.

DNA damage repair (DDR) pathway alteration in advanced renal cell carcinoma (RCC) is association with good progression-free survival with tyrosine kinase inhibitor (TKI) therapy.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 346-346
Author(s):  
Wei Zhai ◽  
Junyun Wang ◽  
Ning He ◽  
Jiale Zhou ◽  
Jianfei Wang ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitor ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Kinase Inhibitor ◽  
Progression Free Survival ◽  
Vascular Endothelial ◽  
Damage Repair ◽  
Endothelial Growth Factor

346 Background: Alterations in DNA damage repair (DDR) genes are associated with human tumorigenesis and may be as potential biomarkers for vascular endothelial growth factor (VEGF) tyrosine kinase inhibitor (TKI) therapy in renal cell carcinoma. However, biologic significance and relevance to TKI targeted therapy in metastatic RCC are unknown. Methods: Genomic data and treatment outcomes were retrospectively collected for patients with metastatic RCC. Tumor and germline DNA were subject to targeted next generation sequencing across 642 genes of interest, including 60 DDR genes. Patients were dichotomized according to underlying DDR gene alteration into (1) DDR gene alterations present (Mut DDR); (2) wildtype (WT) DDR gene alterations present (WT DDR). Association between DDR status and therapeutic benefit was investigated separately for and vascular endothelial growth factor (VEGF) tyrosine kinase inhibitor (TKI) therapy. Results: Mut DDR were detected in 17/40 patients (42.5%). The most frequently DDR altered genes were TP53. For patients with TKI treatment, Mut DDR status was associated with superior progression free survival (log-rank p = 0.048), but not with superior overall survival (log-rank p = 0.39); after adjusting for International Metastatic Renal Cell Carcinoma Database Consortium risks and extent of prior therapy, the HR for Mut DDR was 2.68 (95% CI: 0.96–7.46; p = 0.059). Conclusions: DDR alterations are recurrent genomic events in patients with advanced RCC and were mostly clonal in this cohort. Dysfunction events in these genes may affect outcome with TKI therapy in adanced RCC, and these hypothesis-generating results deserve further study.

scholarly journals Cabozantinib for the Management of Metastatic Clear Cell Renal Cell Carcinoma

2018 ◽  
Vol 5 (4) ◽  
pp. 1-5 ◽  
Author(s):  
Sharon Del Vecchio ◽  
Robert J Ellis
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Kinase Inhibitor ◽  
Progression Free Survival ◽  
Current Treatment ◽  
Phase Iii ◽  
Solid Organ ◽  
Cell Renal Cell Carcinoma ◽  
Randomised Controlled

Cabozantinib is a multi-tyrosine kinase inhibitor used for the treatment of various solid-organ tumours. It was recently approved as a first- and second-line therapeutic for the management of advanced/metastatic renal cell carcinoma based on the results of two randomised controlled trials. The phase III METEOR trial compared cabozantinib against everolimus as a second- or greater line therapy and found benefits in progression-free and overall survival, and the phase II CABOSUN trial compared cabozantinib against sunitinib as a first-line therapeutic and found benefits in terms of progression-free survival. This review briefly summarises how cabozantinib fits into current treatment paradigms for the management of advanced renal cell carcinoma.

scholarly journals Preoperative Plasma Fibrinogen: An Independent Predictor for Survival in Adult Patients with Xp11.2 Translocation Renal Cell Carcinoma

2020 ◽  
Author(s):  
Jie Dong ◽  
Weifeng Xu ◽  
Zhigang Ji ◽  
Boju Pan
Keyword(s):  
Risk Factors ◽  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Distant Metastasis ◽  
Renal Cell ◽  
Cox Regression ◽  
Progression Free Survival ◽  
Adult Patients ◽  
Plasma Fibrinogen ◽  
Xp11.2 Translocation

Abstract Background. Xp11.2 translocation renal cell carcinoma, a rare malignancy, is more common in children than in adults. It manifests with an aggressive course in adults and relatively indolent in children. Prognostic studies for adult patients are scare for the rarity of the disease; and the prognostic value of preoperative plasma fibrinogen awaits further illumination.Methods. This retrospective single-center study enrolled 24 consecutive newly diagnosed Xp11.2 translocation RCC adult patients. Clinical presentations, baseline laboratory results and follow-up data were collected. Possible risk factors for progression free survival and overall survival were first scanned with chi-square tests and t-tests to compare patients who suffered from progression or death and who did not. Multivariate Cox regression was further utilized to identify independent risk factors.Results. Twenty-four adult patients (median age 32, range 16-73), with a male-to-female ratio of 1:1, was included from 2010.4 to 2020.3. After a mean follow-up of 35.7months, seven patients died. With univariate analysis, higher C-reactive protein-to-albumin ratio (p=0.028), higher baseline fibrinogen (p=0.006), and presence of distant metastasis (p=0.007) were associated with progression of disease; higher preoperative fibrinogen (p=0.014) and distant metastasis (p=0.020) were associated with death. With multivariate Cox regression, only baseline fibrinogen level (p=0.001) was identified as an independent risk factor for progression free survival; meanwhile, fibrinogen level (p=0.048) and distant metastasis (p=0.043) were identified as independent risk factors for survival.Conclusions. Preoperative plasma fibrinogen, a routinely tested parameter before surgery, is a promising tool for risk stratification in adult patients with Xp11.2 translocation renal cell carcinoma.JIE et al: Preoperative plasma fibrinogen predicts outcome in Xp11.2 translocation RCC

scholarly journals Metastatic renal cell carcinoma, the possibility of targeted therapy. Case.

2021 ◽  
pp. 138-144
Author(s):  
K. V. Menshikov ◽  
A. A. Izmailov ◽  
A. V. Sultanbaev ◽  
Sh. I. Musin ◽  
V. S. Chalov ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Growth Factor ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitor ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Kinase Inhibitor ◽  
Growth Factor Receptor ◽  
Malignant Neoplasms

Malignant neoplasms of the kidney are quite an urgent problem. In the Russian Federation in 2019, 20758 patients with a newly diagnosed renal cell carcinoma were registered; it should be noted that at the end of 2019, 177 755 patients with this diagnosis were registered. Clear cell carcinoma of the kidney is the most common (75–80%) and most studied subtype of renal cell carcinoma. Because renal cell carcinoma is resistant to chemotherapy, interleukin-2 or interferon alpha has previously been widely used as the first line of treatment for metastatic disease. Sunitinib is an oral tyrosine kinase inhibitor that includes the vascular endothelial growth factor receptor (VEGFR) and the platelet growth factor receptor (PDGFR). Two phase II studies of sunitinib as an anti-angiogenic agent have shown clinical efficacy in patients who progressed on cytokine therapy. Currently, in connection with the development of immuno-oncological drugs, tyrosine kinase inhibitors are fading into the background. It should also be noted that immuno-oncological drugs have their own spectrum of contraindications and immune-mediated toxicity. A clinical case of treatment of a patient with metastatic renal cell carcinoma in the group with a favorable prognosis for IMDC and contraindications to immunotherapy is presented. A history of autoimmune thyroiditis, which was previously treated with levothyroxine sodium, contraindicated treatment with checkpoint inhibitors. The  patient started therapy with the  tyrosine kinase inhibitor sunitinib. Sunitinib therapy made it possible to achieve disease control for  more than 4  years with satisfactory tolerance. The noted adverse events were stopped during therapy and did not lead to a reduction in doses of sunitinib and its cancellation. 

scholarly journals Treatment Options in Metastatic Renal Cell Carcinoma: Focus on mTOR Inhibitors

2010 ◽  
Vol 4 ◽  
pp. CMO.S1590 ◽  
Author(s):  
Sumanta Kumar Pal ◽  
Robert A. Figlin
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Treatment Options ◽  
Mammalian Target Of Rapamycin ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Mtor Inhibitors ◽  
Phase Iii

The agents currently approved for use in metastatic renal cell carcinoma (mRCC) can be divided broadly into two categories: (1) vascular endothelial growth factor receptor (VEGFR)-directed therapies or (2) inhibitors of the mammalian target of rapamycin (mTOR). The latter category includes everolimus and temsirolimus, both approved for distinct indications in mRCC. Everolimus gained its approval on the basis of phase III data showing a benefit in progression-free survival relative to placebo in patients previously treated with sunitinib and/or sorafenib. In contrast, temsirolimus was approved on the basis of a phase III trial in treatment-naïve patients with poor-risk mRCC, demonstrating an improvement in overall survival relative to interferon-alfa. While these pivotal trials have created unique positions for everolimus and temsirolimus in current clinical algorithms, the role of mTOR inhibitors in mRCC is being steadily revised and expanded through ongoing trials testing novel sequences and combinations. The clinical development of mTOR inhibitors is outlined herein.

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