Advanced renal cell carcinoma (RCC) management: an expert panel recommendation from the Latin American Cooperative Oncology Group (LACOG) and the Latin American Renal Cancer Group (LARCG)

Soares, Andrey; Monteiro, Fernando Sabino Marques; Maluf, Fernando C.; Bastos, Diogo Assed; Jardim, Denis Leonardo Fontes; Sasse, André Deeke; Silva, Adriano Gonçalves e; Fay, André P.; Rosa, Diogo Augusto Rodrigues da; Wierman, Evanius; Kater, Fabio; Schutz, Fabio A.B.; Oliveira, Fernando Nunes; Morbeck, Igor Alexandre Protzner; Rinck, José Augusto; Trindade, Karine Martins da; Maia, Manuel Caitano; Souza, Vinicius Carrera; Neto, Deusdedit Cortêz Vieira da Silva; Paula, Felipe de Almeida e; Korkes, Fernando; Carvalhal, Gustavo F.; Nogueira, Lucas; Fernandes, Roni de Carvalho; Reis, Rodolfo Borges dos; Matheus, Wagner Eduardo; Busato, Wilson Francisco Schreiner; Costa, Walter Henriques da; Zéqui, Stênio de Cássio

doi:10.1007/s00432-020-03236-4

Cited by 5 publications

(4 citation statements)

References 99 publications

(195 reference statements)

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“…Cabozantinib is a tyrosine kinase inhibitor (RTK); which is often seen overexpressed in the outer layer of the cancerous tissues. From recent studies, it was confirmed that Cabozantinib specifically targets endothelial growth factor receptor types 1 (VEGFR-1) ( 6 ), endothelial growth factor receptor types 2 (VEGFR-2) ( 7 ), FMS-like tyrosine kinase 3 (FLT-3) ( 8 ); which ultimately results in the demotion of angiogenesis and proliferation of malignant tumour ( 9 , 10 ). As far as liver cancer is concerned ( 11 ), it is the sixth most frequently recognized cancer and the fourth leading cause of cancer mortality across the globe ( 12 , 13 ).…”

Section: Introductionmentioning

confidence: 99%

Unveiling the therapeutic potential of cabozantinib-loaded poly D,L-lactic-co-glycolic acid and polysarcosine nanoparticles in inducing apoptosis and cytotoxicity in human HepG2 hepatocellular carcinoma cell lines and in vivo anti-tumor activity in SCID female mice

Bhattacharya

Parihar²,

Prajapati³

2023

Front. Oncol.

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IntroductionThe study aimed to develop a nano-based drug delivery system for the treatment of hepatocellular carcinoma (HCC), a type of liver cancer that accounts for 90% of all liver malignancies. The study focused on the use of cabozantinib (CNB), a potent multikinase inhibitor that targets the VEGF receptor 2, as the chemotherapeutic drug. We developed CNB-loaded nanoparticles made from Poly D, L-lactic-co-glycolic acid, and Polysarcosine (CNB-PLGA-PSar-NPs) for use in human HepG2 cell lines.MethodsBy O/W solvent evaporation method, the polymeric nanoparticles were prepared. The various techniques, such as photon correlation spectroscopy, scanning electron microscopy, and transmission electron microscopy were used, to determine the formulation's particle size, zeta potential, and morphology. SYBR Green/ROX qPCR Master Mix and RT-PCR equipment used to measure liver cancer cell line and tissue mRNA expression and MTT assay to test HepG2 cell cytotoxicity. Cell cycle arrest analysis, annexin V assay, and ZE5 Cell Analyzer apoptosis assay were also performed.ResultsThe results of the study showed that the particle diameters were 192.0 ± 3.67 nm with 0.128 PDI and -24.18 ± 3.34 mV zeta potential. The antiproliferative and proapoptotic effects of CNB-PLGA-PSar-NPs were evaluated using MTT and flow cytometry (FCM). The IC50 value of CNB-PLGA-PSar-NPs was 45.67 µg/mL, 34.73 µg/mL, and 21.56 µg/mL for 24, 48, and 72 h, respectively. The study also found that 11.20% and 36.77% of CNB-PLGA-PSar-NPs-treated cells were apoptotic at 60 µg/mL and 80 µg/mL, respectively, suggesting that the nanoparticles were effective in inducing apoptosis in the cancer cells. It can also conclude that, CNB-PLGA-PSar-NPs inhibit human HepG2 hepatocellular carcinoma cells and kill them by upregulating the tumour suppressor genes MT1F, MT1X, and downregulating MTTP, APOA4. Further in vivo antitumor activity was well reported in SCID female mice.DiscussionOverall, this study suggests that the CNB-PLGA-PSar-NPs are a promising drug delivery system for the treatment of HCC, and further research is needed to investigate their potential in clinical treatment.

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Section: Introductionmentioning

confidence: 99%

Unveiling the therapeutic potential of cabozantinib-loaded poly D,L-lactic-co-glycolic acid and polysarcosine nanoparticles in inducing apoptosis and cytotoxicity in human HepG2 hepatocellular carcinoma cell lines and in vivo anti-tumor activity in SCID female mice

Bhattacharya

Parihar²,

Prajapati³

2023

Front. Oncol.

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“…Combination therapies, based on the rationale that using drugs that work by different mechanisms may decrease the likelihood of cancer resistance, emerged in an effort to improve outcomes. The treatment landscape for first-line therapy has thus changed dramatically in recent years with the publication of a phase III clinical trial (CT) that showed three combinations’ advantage over sunitinib: (1) Nivolumab/ipili-mumab (Checkmate-214), which proved a higher overall survival (OS), PFS, and ORR in intermediate and high-risk patients[ 4 , 5 ]; (2) Avelumab/axitinib, which showed longer PFS (JAVELIN Renal 101)[ 6 ]; and (3) Pembrolizumab/axitinib, which proved higher in OS, PFS, and ORR among all International Metastatic RCC Database Consortium (IMDC) risk patients (KEYNOTE-426)[ 7 ]. This work has led to the current standard practice recommendations set in the European Association of Urology[ 8 ], ESMO[ 9 ], and National Comprehensive Cancer Network guidelines[ 10 ].…”

Section: Introductionmentioning

confidence: 99%

Update on the treatment of metastatic renal cell carcinoma

López¹,

Belenchón²,

Mazuecos-Quirós³

et al. 2022

WJCO

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Metastatic renal cell cancer (mRCC) management has undergone a paradigm shift in recent decades. The first revolution came with the emergence of vascular endothelial growth factor inhibitors; there was a second wave with the unprecedented success of checkpoint inhibitors, and then the latest approach, which is becoming the new care standard in mRCC, of combining these two strategies in different ways. Updated results of Checkmate-214 after 42 mo of follow-up were consistent with previously published results showing the superiority of nivolumab/ipilimumab over sunitinib in progression free survival (PFS), overall survival (OS), and objective response rate (ORR) in intermediate and high-risk patients. However, several studies presented at the American Society of Clinical Oncology 2020 suggested that the best place, and so far, the only one for nivolumab/ipilimumab is the frontline setting. The update on Keynote-426 after 23 mo of follow-up showed no superiority of pembroli-zumab/axitinib over sunitinib in favorable-risk mRCC, suggesting that it should no longer be the first line of choice in low-risk patients. Finally, the phase III Checkmate 9ER trial results revealed the superiority of nivolumab/cabozantinib vs sunitinib in PFS, OS, and ORR, providing a new first-line option among all International Metastatic RCC Database Consortium risk patients. Some phase II clinical trials also presented this year showed promising results with new combination therapies such as nivolumab/sitravatinib, cabozantinib/atezolizumab, and lenvatinib/pembrolizumab, providing promising grounds upon which to start phase III studies. In addition, other works are using novel therapeutic agents with different mechanisms of action, including telaglenastat (a glutaminase inhibitor), entinostat [an inhibitor of histone deacetylases (HDACs)], and olaparib and talazoparib, poly(ADP-ribose) polymerase inhibitors widely used in other tumors. However, some questions regarding mRCC management still need to be addressed, such as head-to-head comparisons between the current options, treatment sequencing, non-clear cell mRCC, and the role of biomarkers to ascertain the best treatment choice.

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“…Renal cell carcinoma (RCC) is the most common renal neoplasm ( 1 ) and approximately 30% of patients present with metastatic disease ( 2 ), thus, aggravating the mortality of RCC. In the last decade, medical treatment for RCC has laid great emphasis on vascular endothelial growth factor receptor (VEGFR) monoclonal antibody and tyrosine kinase inhibitors (TKI) ( 3 ). These VEGF targeted therapies have improved clinical outcomes by suppressing endothelial cell proliferation and reforming carcinoma vasculature.…”

Section: Introductionmentioning

confidence: 99%

Balancing the Risk-Benefit Ratio of Immune Checkpoint Inhibitor and Anti-VEGF Combination Therapy in Renal Cell Carcinoma: A Systematic Review and Meta-Analysis

Zhang

et al. 2021

Front. Oncol.

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BackgroundAlthough immune checkpoint inhibitors (ICIs) combined with vascular endothelial growth factor receptor (VEGFR)-targeted therapy and sunitinib monotherapy have been widely applied to metastatic renal cell carcinoma (mRCC), effectiveness and safety data are still lacking. To optimize clinical decision-making, we conducted a systematic review and meta-analysis of published randomized clinical trials to characterize the efficacy and the risk of adverse events (AEs) in patients treated with ICIs plus anti-VEGF therapy.Materials and MethodsWe used PubMed, EMBASE, and the Cochrane Library to retrieve randomized controlled trials (RCTs) published before March 27, 2021. The efficacy outcomes were progression-free survival (PFS), overall survival (OS), and objective response rate (ORR). The pooled risk ratio (RR) and 95% confidence intervals (CI) of AEs were calculated in the safety analysis.ResultsSix RCTs involving 4,227 patients were identified after a systematic search. For OS, ICI and anti-VEGF combination therapy decreased mortality approximately 30% in the intention-to-treat population (ITT) (hazard ratio (HR) = 0.70, 95% CI: 0.57–0.87), but there was no statistical difference in patients evaluated as “favorable” by the International Metastatic Renal-Cell Carcinoma Database Consortium (IMDC) criteria compared with monotherapy (HR = 0.90, 95% CI: 0.55–1.46, p = 0.66). In terms of PFS, the progression risk for all participants declined 35% (HR = 0.65, 95% CI: 0.50–0.83) and patients evaluated as “poor” by IMDC benefited further (HR = 0.46, 95% CI: 0.36–0.58). No evident divergence was found in age and sex subgroups. The RRs of all-grade hypertension, arthralgia, rash, proteinuria, high-grade (grades 3–5) arthralgia, and proteinuria developed after combination therapy were increased compared with sunitinib. The risk of high-grade hypertension and rash showed no statistical difference. However, the risk of hand-foot skin reaction (HFSR), stomatitis, and dysgeusia decreased in combination therapy groups.ConclusionsCompared with sunitinib, OS, PFS, and ORR were significantly improved in patients receiving ICI and anti-VEGF combination therapy at the expense of increased specific AEs. More attention should be paid to individualized application of these combination therapies to achieve the best benefit-risk ratio in the clinic.Systematic Review Registration[https://inplasy.com/] INPLASY: 202130104.

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Advanced renal cell carcinoma (RCC) management: an expert panel recommendation from the Latin American Cooperative Oncology Group (LACOG) and the Latin American Renal Cancer Group (LARCG)

Cited by 5 publications

References 99 publications

Unveiling the therapeutic potential of cabozantinib-loaded poly D,L-lactic-co-glycolic acid and polysarcosine nanoparticles in inducing apoptosis and cytotoxicity in human HepG2 hepatocellular carcinoma cell lines and in vivo anti-tumor activity in SCID female mice

Unveiling the therapeutic potential of cabozantinib-loaded poly D,L-lactic-co-glycolic acid and polysarcosine nanoparticles in inducing apoptosis and cytotoxicity in human HepG2 hepatocellular carcinoma cell lines and in vivo anti-tumor activity in SCID female mice

Update on the treatment of metastatic renal cell carcinoma

Balancing the Risk-Benefit Ratio of Immune Checkpoint Inhibitor and Anti-VEGF Combination Therapy in Renal Cell Carcinoma: A Systematic Review and Meta-Analysis

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