scholarly journals Cabozantinib in metastatic renal cell carcinoma: latest findings and clinical potential

2017 ◽  
Vol 9 (10) ◽  
pp. 627-636 ◽  
Author(s):  
Melissa Bersanelli ◽  
Sebastiano Buti
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Kinase Inhibitors ◽  
Wide Spectrum ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Immune Checkpoint Blockade ◽  
Endothelial Growth Factor

Since the advent of immunotherapy revolutionized the treatment of metastatic renal cell carcinoma (mRCC), the attention of oncologists has been unavoidably shifted from tyrosine kinase inhibitors (TKIs) to immune checkpoint blockade, with the associated risk of listing cabozantinib as just one of many available TKIs. On the contrary, we think that cabozantinib represents a very good option for mRCC treatment, with outstanding outcomes in terms of response rate, progression-free survival, overall survival and quick time to treatment response. Its safety profile is acceptable and its discontinuation rate, due to toxicity, is similar to those of other TKIs. It is still not clear if the effectiveness of this drug is justified by its wide spectrum of multikinase activity, extended to the MET and AXL kinases, or by the simple maintenance of a ‘vascular endothelial growth factor receptor pressure’ after another previous TKI. Early-phase studies are currently ongoing to investigate the potential activity and safety of cabozantinib in association with immunotherapy, albeit with the risk of an overly toxic combination. Thus, future opportunities to improve the clinical use of this drug will probably be represented by a smart treatment sequence.

scholarly journals Biomarker Development for Metastatic Renal Cell Carcinoma: Omics, Antigens, T-cells, and Beyond

2020 ◽  
Vol 10 (4) ◽  
pp. 225
Author(s):  
Benjamin Miron ◽  
David Xu ◽  
Matthew Zibelman
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Kinase Inhibitors ◽  
Predictive Biomarkers ◽  
Immune Checkpoint Blockade ◽  
Optimal Sequence ◽  
To Come ◽  
Endothelial Growth Factor

The treatment of metastatic renal cell carcinoma has evolved quickly over the last few years from a disease managed primarily with sequential oral tyrosine kinase inhibitors (TKIs) targeting the vascular endothelial growth factor (VEGF) pathway, to now with a combination of therapies incorporating immune checkpoint blockade (ICB). Patient outcomes have improved with these innovations, however, controversy persists regarding optimal sequence and patient selection amongst the available combinations. Ideally, predictive biomarkers would aid in guiding treatment decisions and personalizing care. However, clinically-actionable biomarkers have remained elusive. We aim to review the available evidence regarding biomarkers for both TKIs and ICB and will present where the field may be headed in the years to come.

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.

Genomic alterations to refine prognostication of patients with metastatic renal cell carcinoma.

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 626-626 ◽  
Author(s):  
Dominick Bosse ◽  
Wanling Xie ◽  
Aly-Khan A. Lalani ◽  
Guillermo de Velasco ◽  
Martin Henner Voss ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Prognostic Value ◽  
Kinase Inhibitors ◽  
Cox Regression ◽  
Risk Groups ◽  
Genomic Alterations ◽  
Endothelial Growth Factor

626 Background: The IMDC risk score is a valid and simple tool to prognosticate patients (pts) with metastatic renal cell carcinoma (mRCC). Some non-VHL common genomic alterations may be associated with outcomes. We therefore assessed the prognostic value of most commonly mutated genes in mRCC beside VHL overall, and within IMDC risk groups. Methods: We identified patients treated at Dana-Farber Cancer Institute (n = 65) or part of TCGA (n = 33) who had genomic data available and were treated with first line vascular endothelial growth factor tyrosine kinase inhibitors. Information on genomic alterations (GA) focused on PBRM1, BAP1, SETD2, KDM5C and TP53 was extracted. Cox regression was performed to assess the association of each GA with overall survival (OS), adjusting for IMDC risk groups and age. Results: Overall, 98 pts were identified. 96/98 pts had clear-cell histology. Pts distribution by IMDC risk groups was: 7% good, 58% intermediate, 27% poor and 8% unknown. Mutation rates were 27% PBRM1, 17% BAP1, 29% SETD2, 9% KDM5C and 8% TP53. In multivariable models, there was an association between GA and worse OS for BAP1 and BAP1 or TP53 combined (Table). When stratified by IMDC risk groups, GA in BAP1 or TP53 was associated with shorter median OS in poor risk pts [12.1 mo (95%CI 8.3- 24.0) v. 27.6 mo (95%CI 18.9- 53.4), aHR 4.64 (95%CI 1.32-16.4), p = 0.017] and a trend toward worse median OS in intermediate risk pts [20.5 mo (95%CI 7.4-54.6) v. 36.3 mo (95%CI 21.1, NR), aHR 2.11 (95%CI 0.94-4.74)] compared to pts without GA in BAP1 or TP53. Too few death events were observed in good risk pts to assess the prognostic value of GA in BAP1 or TP53. Conclusions: GA in BAP1 or TP53 are prognostic in mRCC and further discriminate pts with distinct outcomes within IMDC risk groups. Validation in larger dataset is ongoing. [Table: see text]

Treatment Strategies in Metastatic Renal Cell Carcinoma

2010 ◽  
Vol 06 (02) ◽  
pp. 41
Author(s):  
Alain Ravaud ◽  
Jean Christophe Bernhard ◽  
Marine Gross-Goupil ◽  
◽  
◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Mammalian Target Of Rapamycin ◽  
Treatment Strategies ◽  
Growth Factor Receptor ◽  
Clinical Effects ◽  
Improved Outcomes ◽  
Endothelial Growth Factor

Metastatic renal cell carcinoma (mRCC) is associated with a poor clinical outcome. Until recently, treatment recommendations were limited to immunotherapy and nephrectomy; however, an increased understanding of the molecular biology of RCC has led to the advent of targeted therapies directed against vascular endothelial growth factor/receptor (VEGF/VEGFR) or the mammalian target of rapamycin (mTOR) pathways, both major mediators of tumour growth and progression. These targeted agents have significantly improved outcomes in patients with mRCC, revolutionising treatment. These treatments have overlaps and important distinctions in terms of clinical effects, toxicity and patient populations in which they have been investigated. Concerns in terms of the appropriate sequencing of these agents, their combined use and their role in the context of nephrectomy have emerged as clinically relevant and are being actively investigated.

Long progression-free survival with cabozantinib in a heavily pretreated patient with metastatic renal cell carcinoma: a case report

2021 ◽  
pp. 030089162199073
Author(s):  
Cecilia Nasso ◽  
Roberto Sabbatini ◽  
Cinzia Baldessari ◽  
Massimo Dominici ◽  
Maria Giuseppa Vitale
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Kinase Inhibitors ◽  
Progression Free Survival ◽  
Free Survival ◽  
Heavily Pretreated ◽  
Pretreated Patients

Renal cell carcinoma accounts for 3% of all tumors. Over the last decades, the prognosis of metastatic renal cell carcinoma (mRCC) has improved owing to the approval of several drugs such as tyrosine kinase inhibitors and immunotherapy. The median progression-free survival (PFS) does not exceed 8 months with the available drugs in pretreated patients with mRCC. We present a case of a patient with a long-term response to fourth-line treatment with cabozantinib. Our patient obtained a PFS of 33 months, which is much higher than that reported in literature.

Efficacy and safety of sequential use of everolimus in patients with metastatic renal cell carcinoma previously treated by bevacizumab with or without interferon therapy: Results from pooled analysis of AVATOR, CHANGE, and TRAIN studies.

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 585-585
Author(s):  
Antoine Thiery- Vuillemin ◽  
Aline Guillot ◽  
Thomas Steiner ◽  
Edwin Herrmann ◽  
Konstantinos N. Syrigos ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Kinase Inhibitors ◽  
Mammalian Target Of Rapamycin ◽  
Growth Factor Receptor ◽  
Pooled Analysis ◽  
Second Line ◽  
Line Therapy

585 Background: Everolimus is a mammalian target of rapamycin (mTOR) inhibitor. It gained approval based on the results of the RECORD-1 trial, which included patients with metastatic renal cell carcinoma (mRCC) whose disease progressed after receiving vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKIs). Bevacizumab is a monoclonal antibody targeting angiogenesis that is approved in patients (pts) with mRCC. AVATOR was the 1st study to explore the sequential use of bevacizumab followed by everolimus but with limited number of pts. Methods: In order to further explore this sequence pooled data from the AVATOR, CHANGE and TRAIN studies were analysed retrospectively. All pts had mRCC and were previously or currently treated with everolimus after failure of bevacizumab ± IFN. The primary end point was everolimus time to progression (TTP). Secondary end points were related to the overall survival (OS) of patients receiving the drug sequence, everolimus treatment and safety. Results: 89 pts were included in the analysis. Median age was 68 years [18-90]. At everolimus initiation ECOG was 0-1 for 72% pts and 16% were classified as poor prognosis from Heng classification. Exploring the duration of second-line everolimus treatment, 32% of patients received less than 3 months of everolimus and 35% received at least 6 months of treatment. At the time of data analysis, 20 pts (24%) were still receiving everolimus. Pts receiving everolimus after bevacizumab experienced a median TTP of 6 months [95%CI 4 - 14]. Median OS was not reached for everolimus second-line therapy. At 36 months after the start of first-line therapy, 60.4% of pts were still alive. All grades of common adverse events were consistent with the known safety profile of everolimus. Conclusions: The larger size of this cohort confirms the signal previously seen with AVATOR that the sequence of bevacizumab followed by everolimus displays interesting efficacy with not unexpected toxicity from everolimus and compares favourably with RECORD-1.

Severe sunitinib-induced myelosuppression in a patient with a CYP 3A4 polymorphism

2017 ◽  
Vol 24 (8) ◽  
pp. 623-626 ◽  
Author(s):  
Nirav D Patel ◽  
Kanishka Chakrabory ◽  
Garrett Messmer ◽  
Koyamangalath Krishnan ◽  
John B Bossaer
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Growth Factor Receptor ◽  
Skin Reactions ◽  
Current State ◽  
Early Grade ◽  
Grade 3 ◽  
Endothelial Growth Factor

Sunitinib, an oral vascular endothelial growth factor receptor, is a first-line option for metastatic renal cell carcinoma and widely used in clinical practice. Despite the proven benefit of sunitnib in metastatic renal cell carcinoma, patients may suffer from a variety of adverse events including hypertension, fatigue, hypothyroidism, hand–foot skin reactions, rash, depigmentation, and myelosuppression. Myelosuppression is usually mild, transient and resolves during the two weeks at the end of each cycle where no drug is taken. We present a case of severe and early grade 3 neutropenia and thrombocytopenia occurring two weeks into a six-week cycle. Because of the extreme nature of the toxicity, CYP 3A4 polymorphisms were explored. The patient was found to be heterozygous for CYP 3A4*22, at least partially explaining the early-onset and severity of myelosuppression. This pharmacogenetics information resulted in a rechallenge of dose-reduced sunitinib, which was well tolerated by the patient. The current state of pharmacogenomics concerning sunitinb is also presented, and the need for greater research in this area is highlighted.

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