Survival Benefits of Second-line Axitinib Versus Everolimus After First Line Sunitinib Treatment in Metastatic Renal Cell Carcinoma

Gergely, Lajos; Bodoky, G.; Rokszin, György; Fábián, Ibolya; Torday, Laszlo

doi:10.1007/s12253-020-00809-z

Cited by 7 publications

(5 citation statements)

References 40 publications

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“…Nevertheless, the frequency up to the fourth line of therapy was similar across all three groups studied, while prolongation of OS was independent of IMDC categorization, except for Group C. It was also not dependent on the choice of first-line agent or the timing of use of axitinib, cabozantinib, and nivolumab. Median OS and landmark survival rates in our series were similar to that described in real-world studies from other countries, but also to that of populations included in contemporary clinical trials [15,16]. Importantly, the reported survival is numerically longer than that reported for similar patients treated in the same centers during the period before the widespread introduction of the three agents studied in this series [12,17].…”

Section: Discussionsupporting

confidence: 85%

Outcomes from treatment of metastatic renal-cell carcinoma following failure of first-line anti-VEGF/VEGFR therapy: real-life evidence on the change of the treatment paradigm

et al. 2022

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Recently approved agents for post-vascular endothelial growth factor/post-vascular endothelial growth factor receptor (VEGF/VEGFR) inhibitors treatment of metastatic renal-cell carcinomas (mRCC), such as axitinib, nivolumab, and cabozantinib were shown to improve prognosis and substituted everolimus in this setting. We studied practice patterns, efficacy, and tolerability of these agents in a real-world series of Greek patients. We included patients with mRCC who received everolimus, axitinib, or nivolumab after progression on first-line anti-VEGF/VEGFRs therapy. Patients were stratified into three groups. Group A received nivolumab with or without cabozantinib at some point in their disease. Group B received axitinib but without nivolumab or cabozantinib. Group C received only everolimus among the four approved agents. Overall, 131 patients were included in the analysis. Everolimus and nivolumab were mainly used in the second line, while axitinib and cabozantinib were mostly used in the third and fourth lines. Median overall survival (OS) from first-line initiation was 8.7 [95% confidence interval (CI), 4–not reached], 3.6 (95% CI, 2–6), and 2.1 years (95% CI, 1.4–2.6) for Group A, B, and C, respectively (P < 0.001). Median OS from the initiation of second-line therapy was 3.5, 2.7, and 1.3 years, respectively (P < 0.001). There was no impact of first-line agent or treatment timing on survival. International Metastatic Renal Cell Carcinoma Database Consortium risk stratification was associated with OS. Toxicities observed were within expected frequencies. Grade ≥3 events were rare. Adoption of modern standards in everyday treatment of mRCC results in prolongation of survival. Real-world datasets are the new landmarks of survival for future research.

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Section: Discussionsupporting

confidence: 85%

Outcomes from treatment of metastatic renal-cell carcinoma following failure of first-line anti-VEGF/VEGFR therapy: real-life evidence on the change of the treatment paradigm

et al. 2022

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“…[64][65][66][67][68] Second-line axitinib also exhibits a favorable survival benefit after first-line sunitinib treatment in metastatic RCC. 69 In our study, we also evaluated the sensitivity of patients with ccRCC to cisplatin and docetaxel and confirmed that the low-risk group displayed higher sensitivity to all six drugs. In this sense, the low-risk population may receive more benefits from these drugs.…”

Section: Discussionsupporting

confidence: 64%

Development of an Interferon Gamma Response-Related Signature for Prediction of Survival in Clear Cell Renal Cell Carcinoma

Liu

Fang

et al. 2021

JIR

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Background Interferon plays a crucial role in the pathogenesis and progression of tumors. Clear cell renal cell carcinoma (ccRCC) represents a prevalent malignant urinary system tumor. An effective predictive model is required to evaluate the prognosis of patients to optimize treatment. Materials and Methods RNA-sequencing data and clinicopathological data from TCGA were involved in this retrospective study. The IFN-γ response genes with significantly different gene expression were screened out. Univariate Cox regression, LASSO regression and multivariate Cox regression were used to establish a new prognostic scoring model for the training group. Survival curves and ROC curves were drawn, and nomogram was constructed. At the same time, we conducted subgroup analysis and experimental verification using our own samples. Finally, we evaluated the relatedness between the prognostic signature and immune infiltration landscapes. In addition, the sensitivity of different risk groups to six drugs and immune checkpoint inhibitors was calculated. Results The IFN-γ response-related signature included 7 genes: C1S, IFI44, ST3GAL5, NUP93, TDRD7, DDX60, and ST8SIA4. The survival curves of the training and testing groups showed the model’s effectiveness (P = 4.372e-11 and P = 1.08e-08, respectively), the ROC curves showed that the signature was stable, and subgroup analyses showed the wide applicability of the model (P<0.001). Multivariate Cox regression analysis showed that the risk model was an independent prognostic factor of ccRCC. A high-risk score may represent an immunosuppressive microenvironment, while the high-risk group exhibited poor sensitivity to drugs. Conclusion Our findings strongly indicate that the IFN-γ response-related signature can be used as an effective prognostic indicator of ccRCC.

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“…However, the role of MICAL-L2 in the therapy of renal cancer is rarely investigated. Sunitinib and everolimus-based therapy is the main drug therapy approach for metastatic renal cell carcinoma and is frequently combined with other agents in clinical practice [21,34,35]. Everolimus is a derivative of rapamycin and acts similarly to rapamycin as an mTOR inhibitor.…”

Section: Discussionmentioning

confidence: 99%

High MICAL-L2 promotes cancer progression and drug resistance of renal clear cell carcinoma cell via stabilization of ACTN4 and following vimentin expression

Du,

Zhao,

et al. 2024

Preprint

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Kidney clear cell carcinoma (KIRC) continues to be a substantial contributor to cancer-associated fatalities nowadays. Targeted therapies persist as the conventional method of KIRC treatment. Nevertheless, the development of resistance to those drug emerges as a significant impediment to renal cancer management. MICALL2, a member of the molecules that interact with the CasL family (MICALs), plays pivotal roles in cytoskeleton rearrangement. This study sought to elucidate the clinical relevance of MICAL-L2 in KIRC and its regulatory mechanism in cancer progression and resistance to therapy. The Cancer Genome Atlas data mining was utilized to assess the expression of MICAL-L2 in KIRC tissues. Statistical analysis of immunohistochemistry and the Kaplan–Meier Plotter database were employed to investigate the clinical significance of MICALL2. A series of in vitro experiments, encompassing assays for CCK-8, EDU staining, wound healing and transwell migration, flow cytometry, RT-PCR, co-immunoprecipitation analysis were conducted to demonstrate the effects of MICAL-L2 on the drug sensitivity of KIRC cells and to elucidate the underlying molecular mechanisms. MICAL-L2 is overexpressed in KIRC tissues. Elevated MICAL-L2 levels correlate with reduced survival rate and a diminished response to drug therapy in KIRC patients. MICAL-L2 overexpression stimulates cell proliferation, migration and renders KIRC cells insensitive to Sunitinib and Everolimus, two traditional therapeutics for KIRC. Furthermore, MICAL-L2 promotes progression and resistance to therapy in KIRC cells by interacting with its downstream regulator Alpha-actinin-4 (ACTN4) in a Rab13-dependent manner, then reducing ACTN4 degradation, and thereby leading to augmented vimentin expression in KIRC cells. These findings indicate that MICAL-L2 plays a critical role in the progression of KIRC and suggest that MICAL-L2 may function as a therapeutic target in KIRC patients.

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Survival Benefits of Second-line Axitinib Versus Everolimus After First Line Sunitinib Treatment in Metastatic Renal Cell Carcinoma

Cited by 7 publications

References 40 publications

Outcomes from treatment of metastatic renal-cell carcinoma following failure of first-line anti-VEGF/VEGFR therapy: real-life evidence on the change of the treatment paradigm

Outcomes from treatment of metastatic renal-cell carcinoma following failure of first-line anti-VEGF/VEGFR therapy: real-life evidence on the change of the treatment paradigm

Development of an Interferon Gamma Response-Related Signature for Prediction of Survival in Clear Cell Renal Cell Carcinoma

High MICAL-L2 promotes cancer progression and drug resistance of renal clear cell carcinoma cell via stabilization of ACTN4 and following vimentin expression

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