The role of the MET/AXL pathway as a new target for multikinase inhibitors in renal cell carcinoma

Nunno, Vincenzo Di; Cubelli, Marta; Massari, Francesco

doi:10.1080/23808993.2017.1347481

Cited by 8 publications

(6 citation statements)

References 66 publications

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“…Cabozantinib is an orally administered tyrosine kinase inhibitor (TKI) acting mainly on VEGFR2 (VEGF receptor 2), MET (mesenchymal epithelial transition receptor), and AXL (anexelekto pathway) [ 9 ]. Currently, cabozantinib is approved for the treatment of patients with metastatic RCC in treatment-naïve adults with intermediate or poor-risk features and for adults that have progressed to prior vascular endothelial growth factor/receptor inhibitors.…”

Section: Introductionmentioning

confidence: 99%

Body Mass Index in Patients Treated with Cabozantinib for Advanced Renal Cell Carcinoma: A New Prognostic Factor?

et al. 2021

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We analyzed the clinical and pathological features of renal cell carcinoma (RCC) patients treated with cabozantinib stratified by body mass index (BMI). We retrospectively collected data from 16 worldwide centers involved in the treatment of RCC. Overall survival (OS) and progression-free survival (PFS) were analyzed using Kaplan–Meier curves. Cox proportional models were used at univariate and multivariate analyses. We collected data from 224 patients with advanced RCC receiving cabozantinib as second- (113, 5%) or third-line (111, 5%) therapy. The median PFS was significantly higher in patients with BMI ≥ 25 (9.9 vs. 7.6 months, p < 0.001). The median OS was higher in the BMI ≥ 25 subgroup (30.7 vs. 11.0 months, p = 0.003). As third-line therapy, both median PFS (9.2 months vs. 3.9 months, p = 0.029) and OS (39.4 months vs. 11.5 months, p = 0.039) were longer in patients with BMI ≥ 25. BMI was a significant predictor for both PFS and OS at multivariate analysis. We showed that a BMI ≥ 25 correlates with longer survival in patients receiving cabozantinib. BMI can be easily assessed and should be included in current prognostic criteria for advanced RCC.

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Section: Introductionmentioning

confidence: 99%

Body Mass Index in Patients Treated with Cabozantinib for Advanced Renal Cell Carcinoma: A New Prognostic Factor?

et al. 2021

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“…Cabozantinib is an orally administered tyrosine kinase inhibitor acting mainly on VEGFR2, MET (mesenchymal epithelial transition receptor) and AXL (anexelekto pathway) [14]. In the randomized phase III METEOR trial comparing cabozantinib to everolimus in pretreated patients, cabozantinib improved overall survival (OS), progression-free survival (PFS) and objective response rate (ORR) [15].…”

Section: Introductionmentioning

confidence: 99%

Real-World Data on Cabozantinib in Previously Treated Patients with Metastatic Renal Cell Carcinoma: Focus on Sequences and Prognostic Factors

Santoni

Heng

Bracarda

et al. 2019

Cancers

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Cabozantinib is approved for the treatment of renal cell carcinoma (RCC). However, prognostic factors are still lacking in this context. The aim of this study was to evaluate prognostic factors in RCC patients treated with second- or third-line cabozantinib. A multicenter retrospective real-world study was conducted, involving 32 worldwide centers. A total of 237 patients with histologically confirmed clear-cell and non-clear-cell RCC who received cabozantinib as second- or third-line therapy for metastatic disease were included. We analyzed overall survival (OS), progression-free survival (PFS) and time-to-strategy failure (TTSF) using Kaplan–Meier curves. Cox proportional models were used at univariate and multivariate analyses.The median PFS and OS of cabozantinib were 7.76 months (95% CI 6.51–10.88) and 11.57 months (95% CI 10.90–not reached (NR)) as second-line and 11.38 months (95% CI 5.79–NR) and NR (95% CI 11.51–NR) as third-line therapy. The median TTSF and OS were 11.57 and 15.52 months with the sequence of cabozantinib–nivolumab and 25.64 months and NR with nivolumab–cabozantinib, respectively. The difference between these two sequences was statistically significant only in good-risk patients. In the second-line setting, hemoglobin (Hb) levels (HR= 2.39; 95% CI 1.24–4.60, p = 0.009) and IMDC (International Metastatic Renal Cell Carcinoma Database Consortium) group (HR = 1.72, 95% CI 1.04–2.87, p = 0.037) were associated with PFS while ECOG-PS (HR = 2.33; 95%CI, 1.16–4.69, p = 0.018) and Hb levels (HR = 3.12; 95%CI 1.18–8.26, p = 0.023) correlated with OS at multivariate analysis, while in the third-line setting, only Hb levels (HR = 2.72; 95%CI 1.04–7.09, p = 0.042) were associated with OS. Results are limited by the retrospective nature of the study.This real-world study provides evidence on the presence of prognostic factors in RCC patients receiving cabozantinib.

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“…One of the most important processes driving acquired resistance to VEGF/VEGFR inhibitors is represented by the development of other pathways driving angiogenesis. PDGF/PDGFR and mesenchymal epithelial transition receptor (MET) may be two critical pathways employed by cancer cells to overcome VEGF/VEGFR blockade [36,37,38,39,40].…”

Section: Resistance To Target Therapymentioning

confidence: 99%

Resistance to Systemic Agents in Renal Cell Carcinoma Predict and Overcome Genomic Strategies Adopted by Tumor

Mollica

Nunno

Gatto

et al. 2019

Cancers

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The development of new systemic agents has led us into a “golden era” of management of metastatic renal cell carcinoma (RCC). Certainly, the approval of immune-checkpoint inhibitors and the combination of these with targeted compounds has irreversibly changed clinical scenarios. A deeper knowledge of the molecular mechanisms that correlate with tumor development and progression has made this revolution possible. In this amazing era, novel challenges are awaiting us in the clinical management of metastatic RCC. Of these, the development of reliable criteria which are able to predict tumor response to treatment or primary and acquired resistance to systemic treatments still remain an unmet clinical need. Thanks to the availability of data provided by studies evaluating genomic assessments of the disease, this goal may no longer be out of reach. In this review, we summarize current knowledge about genomic alterations related to primary and secondary resistance to target therapy and immune-checkpoint inhibitors in RCC.

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The role of the MET/AXL pathway as a new target for multikinase inhibitors in renal cell carcinoma

Cited by 8 publications

References 66 publications

Body Mass Index in Patients Treated with Cabozantinib for Advanced Renal Cell Carcinoma: A New Prognostic Factor?

Body Mass Index in Patients Treated with Cabozantinib for Advanced Renal Cell Carcinoma: A New Prognostic Factor?

Real-World Data on Cabozantinib in Previously Treated Patients with Metastatic Renal Cell Carcinoma: Focus on Sequences and Prognostic Factors

Resistance to Systemic Agents in Renal Cell Carcinoma Predict and Overcome Genomic Strategies Adopted by Tumor

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