Lenvatinib plus pembrolizumab significantly improved efficacy versus sunitinib in treatment of advanced renal cell carcinoma (aRCC) in the phase 3 CLEAR study. We report results of an exploratory post hoc analysis of tumor response data based on baseline metastatic characteristics of patients who received lenvatinib plus pembrolizumab versus sunitinib, at the final overall survival analysis time point of CLEAR (cutoff: July 31, 2022). Treatment-naïve adults with aRCC were randomized to: lenvatinib (20 mg PO QD in 21-day cycles) plus pembrolizumab (n = 355; 200 mg IV Q3W); lenvatinib plus everolimus (not reported here); or sunitinib (n = 357; 50 mg PO QD; 4 weeks on/2 weeks off). The most common (lenvatinib plus pembrolizumab; sunitinib, respectively) metastatic site was lung (71.0%; 63.9%), followed by lymph node (45.6%; 43.7%), bone (22.5%; 24.9%), and liver (17.7%; 19.6%). Across treatment arms, ≥65% had two or more metastatic organs/sites involved, >80% of patients had nontarget lesions, and ~45% had baseline sums of diameters of target lesions ≥60 mm. Lenvatinib plus pembrolizumab demonstrated greater progression-free survival, objective response rate, and duration of response versus sunitinib across evaluable subgroups regardless of site or size of baseline metastasis or number of metastatic sites at baseline. Overall survival generally trended to favor lenvatinib plus pembrolizumab versus sunitinib; and tumor shrinkage was greater across sites (lung, lymph node, liver, and bone) for patients in the lenvatinib-plus-pembrolizumab arm versus the sunitinib arm. These results further support lenvatinib plus pembrolizumab as a standard-of-care in patients with aRCC regardless of site or size of baseline metastasis or the number of metastatic sites.

• Klíčová slova
• lenvatinib, lenvatinib plus pembrolizumab, pembrolizumab, renal cell carcinoma,
• MeSH
• chinoliny * aplikace a dávkování   terapeutické užití   MeSH
• dospělí MeSH
• fenylmočovinové sloučeniny * aplikace a dávkování   terapeutické užití   MeSH
• humanizované monoklonální protilátky * aplikace a dávkování   terapeutické užití   MeSH
• karcinom z renálních buněk * farmakoterapie   patologie   mortalita   sekundární   MeSH
• lidé středního věku MeSH
• lidé MeSH
• metastázy nádorů MeSH
• nádory ledvin * farmakoterapie   patologie   mortalita   MeSH
• protokoly protinádorové kombinované chemoterapie * terapeutické užití   MeSH
• senioři MeSH
• sunitinib * aplikace a dávkování   terapeutické užití   MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• multicentrická studie MeSH
• randomizované kontrolované studie MeSH
• srovnávací studie MeSH
• Názvy látek
• chinoliny * MeSH
• fenylmočovinové sloučeniny * MeSH
• humanizované monoklonální protilátky * MeSH
• lenvatinib MeSH Prohlížeč
• pembrolizumab MeSH Prohlížeč
• sunitinib * MeSH

Clear-cell renal cell carcinoma (ccRCC) is a common urological malignancy with an increasing incidence. The development of molecular biomarkers that can predict the response to treatment and guide personalized therapy selection would substantially improve patient outcomes. Dysregulation of non-coding RNA (ncRNA) has been shown to have a role in the pathogenesis of ccRCC. Thus, an increasing number of studies are being carried out with a focus on the identification of ncRNA biomarkers in ccRCC tissue samples and the connection of these markers with patients' prognosis, pathological stage and grade (including metastatic potential), and therapy outcome. RNA sequencing analysis led to the identification of several ncRNA biomarkers that are dysregulated in ccRCC and might have a role in ccRCC development. These ncRNAs have the potential to be prognostic and predictive biomarkers for ccRCC, with prospective applications in personalized treatment selection. Research on ncRNA biomarkers in ccRCC is advancing, but clinical implementation remains preliminary owing to challenges in validation, standardization and reproducibility. Comprehensive studies and integration of ncRNAs into clinical trials are essential to accelerate the clinical use of these biomarkers.

• MeSH
• karcinom z renálních buněk * genetika   MeSH
• lidé MeSH
• nádorové biomarkery genetika   MeSH
• nádory ledvin * genetika   MeSH
• nekódující RNA * genetika   MeSH
• prognóza MeSH
• transkriptom * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• nádorové biomarkery MeSH
• nekódující RNA * MeSH

INTRODUCTION: The phase 3 CLEAR study demonstrated that lenvatinib plus pembrolizumab significantly improved efficacy versus sunitinib as first-line treatment for patients with advanced renal cell carcinoma (RCC). Prognostic features including presence and/or site of baseline metastases, prior nephrectomy, and sarcomatoid features have been associated with disease and treatment success. This subsequent analysis explores outcomes in patients with or without specific prognostic features. METHODS: In CLEAR, patients with clear cell RCC were randomly assigned (1:1:1) to receive either lenvatinib (20 mg/day) plus pembrolizumab (200 mg every 3 weeks), lenvatinib (18 mg/day) plus everolimus (5 mg/day), or sunitinib alone (50 mg/day, 4 weeks on, 2 weeks off). In this report, progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) were all assessed in the lenvatinib-plus-pembrolizumab and the sunitinib arms, based on baseline features: lung metastases, bone metastases, liver metastases, prior nephrectomy, and sarcomatoid histology. RESULTS: In all the assessed subgroups, median PFS was longer with lenvatinib-plus-pembrolizumab than with sunitinib treatment, notably among patients with baseline bone metastases (HR 0.33, 95% CI 0.21-0.52) and patients with sarcomatoid features (HR 0.39, 95% CI 0.18-0.84). Median OS favored lenvatinib plus pembrolizumab over sunitinib irrespective of metastatic lesions at baseline, prior nephrectomy, and sarcomatoid features. Of interest, among patients with baseline bone metastases the HR for survival was 0.50 (95% CI 0.30-0.83) and among patients with sarcomatoid features the HR for survival was 0.91 (95% CI 0.32-2.58); though for many groups, median OS was not reached. ORR also favored lenvatinib plus pembrolizumab over sunitinib across all subgroups; similarly, complete responses also followed this pattern. CONCLUSION: Efficacy outcomes improved following treatment with lenvatinib-plus-pembrolizumab versus sunitinib in patients with RCC-irrespective of the presence or absence of baseline lung metastases, baseline bone metastases, baseline liver metastases, prior nephrectomy, or sarcomatoid features. These findings corroborate those of the primary CLEAR study analysis in the overall population and support lenvatinib plus pembrolizumab as a standard of care in 1L treatment for patients with advanced RCC. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, identifier NCT02811861.

• Klíčová slova
• bone metastases, lenvatinib, liver metastases, lung metastases, pembrolizumab, renal cell carcinoma, sarcomatoid histology, sunitinib,
• Publikační typ
• časopisecké články MeSH