First-line therapy for adults with advanced renal cell carcinoma: a systematic review and network meta-analysis

Aldin, Angela; Besiroglu, Burcu; Adams, Anne; Monsef, Ina; Piechotta, Vanessa; Tomlinson, E.; Hornbach, Carolin; Dressen, Nadine; Goldkuhle, Marius; Maisch, Philipp; Dahm, Philipp; Heidenreich, Axel; Skoetz, Nicole

doi:10.1002/14651858.cd013798.pub2

Cited by 6 publications

(4 citation statements)

References 441 publications

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“…Результаты приведены в табл. 6 [24,25]. Необходимо учитывать еще одно неочевидное преимущество применения монотерапии тирозинкиназными ингибиторами -возможность предоставления пациентам «терапевтических каникул».…”

Section: Discussionunclassified

Treatment of metastatic сlear cell renal cell carcinoma: focus on a group of patients with favourable prognosis

Rumyantsev

2024

Medicinskij sovet

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Current clinical guidelines of various domestic and foreign professional communities indicate combination regimens as an option for the first-line therapy for metastatic сlear cell renal cell carcinoma, regardless of the patient’s prognosis group. This review article is devoted to the analysis of the current evidence base for the use of different variants of combination therapy regimens in patients with metastatic renal cell carcinoma and assessment of the role of single-component cancer therapy options in the initial treatment of this disease. We reviewed the results of studies of current immuno-oncology therapy regimens in the first-line renal cell carcinoma therapy with a focus on a favourable prognosis group, taking into account the latest updates from the studies evaluating the efficacy of combination treatments (pembrolizumab/axitinib, pembrolizumab/lenvatinib, nivolumab/cabozantinib, avelumab/axitinib). We found that although the use of certain combinations of immunooncology and targeted drugs give better results of disease control, objective response and progression-free survival rates, none of the studied combinations to date has shown a significant increase in overall patient survival rates, which is a key treatment efficacy indicator in metastatic cancer. Conclusions drawn from this review indicate that monotherapy with tyrosine kinase inhibitors, such as sunitinib or pazopanib, appears to be sufficient and optimal from a clinical and economic point of view in the treatment of a favourable prognosis group. For patients with a favourable prognosis, tyrosine kinase inhibitor monotherapy may be a primary rather than an alternative therapeutic option until the benefit of combinations in terms of overall survival rates has been showed.

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Section: Discussionunclassified

Treatment of metastatic сlear cell renal cell carcinoma: focus on a group of patients with favourable prognosis

Rumyantsev

2024

Medicinskij sovet

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“…The treatment landscape for metastatic renal cell carcinoma (mRCC) has dramatically changed over the past few decades with the development of targeted therapies as well as immune checkpoint inhibitors (ICI). First-line therapy options for mRCC currently include dual ICI combinations with anti-CTLA-4 and anti-PD-1 inhibitors (e.g., ipilimumab and nivolumab) and tyrosine kinase inhibitors (TKIs), as well as the combination of ICIs with TKIs [1]. Despite these therapies, the estimated 5-year survival rate for patients with mRCC remains low at 15% [2].…”

Section: Introductionmentioning

confidence: 99%

Novel Approaches with HIF-2α Targeted Therapies in Metastatic Renal Cell Carcinoma

Nguyen,

Oh,

Bahar

et al. 2024

Cancers

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Germline inactivation of the Von Hippel-Lindau (VHL) tumor suppressor is the defining hallmark in hereditary VHL disease and VHL-associated renal cell carcinoma (RCC). However, somatic VHL mutations are also observed in patients with sporadic RCC. Loss of function VHL mutations result in constitutive activation of hypoxia-inducible factor-2 alpha (HIF-2α), which leads to increased expression of HIF target genes that promote angiogenesis and tumor growth. As of 2023, belzutifan is currently the only approved HIF-2α inhibitor for both VHL-associated and sporadic metastatic RCC (mRCC). However, there is potential for resistance with HIF-2α inhibitors which warrants novel HIF-2α-targeting strategies. In this review, we discuss the potential resistance mechanisms with belzutifan and current clinical trials evaluating novel combinations of belzutifan with other targeted therapies and immune checkpoint inhibitors which may enhance the efficacy of HIF-2α targeting. Lastly, we also discuss newer generation HIF-2α inhibitors that are currently under early investigation and outline future directions and challenges with HIF-2α inhibitors for mRCC.

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“…The management of mRCC has undergone significant changes, with innovative combination therapies showing better outcomes compared to traditional monotherapy [ 16 ]. The multidisciplinary tumor board plays a crucial role, especially for patients eligible for local interventions.…”

Section: Introductionmentioning

confidence: 99%

First-Line Treatments and Management of Metastatic Renal Cell Carcinoma Patients: An Italian Interdisciplinary Uro-Oncologic Group Algorithm

Bloise,

Manfredi,

Zatteri

et al. 2024

Cells

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The treatment landscape for metastatic renal cell carcinoma (mRCC) has undergone significant transformations in recent years. The introduction of novel combination therapies involving tyrosine kinase inhibitors (TKI) and immune checkpoint inhibitors has resulted in improved oncological outcomes compared to traditional TKI monotherapy. In this evolving paradigm, the pivotal role of the multidisciplinary tumor board is underscored, particularly in shaping the therapeutic trajectory for patients eligible for locoregional interventions like cytoreductive nephrectomy and metastasectomy. In cases where systemic treatment is deemed appropriate, the absence of direct comparisons among the various combination therapies complicates the selection of a first-line approach. The clinician is faced with the challenge of making decisions based on patient-specific factors such as performance status, risk classification according to the International Metastatic Renal Cell Carcinoma Database Consortium, comorbidities, and disease characteristics, including the number and location of metastases and tumor histology. Considering these concerns, we propose, as a member of a Tuscany Interdisciplinary Uro-Oncologic Group, an algorithm to streamline the decision-making process for mRCC patients, offering guidance to clinicians in their day-to-day clinical practice.

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First-line therapy for adults with advanced renal cell carcinoma: a systematic review and network meta-analysis

Cited by 6 publications

References 441 publications

Treatment of metastatic сlear cell renal cell carcinoma: focus on a group of patients with favourable prognosis

Treatment of metastatic сlear cell renal cell carcinoma: focus on a group of patients with favourable prognosis

Novel Approaches with HIF-2α Targeted Therapies in Metastatic Renal Cell Carcinoma

First-Line Treatments and Management of Metastatic Renal Cell Carcinoma Patients: An Italian Interdisciplinary Uro-Oncologic Group Algorithm

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