The 2021 Updated European Association of Urology Guidelines on Renal Cell Carcinoma: Immune Checkpoint Inhibitor-based Combination Therapies for Treatment-naive Metastatic Clear-cell Renal Cell Carcinoma Are Standard of Care.
German Cancer Research Center1, Université Paris-Saclay2, Vita-Salute San Raffaele University3, Charles University in Prague4, Aberdeen Royal Infirmary5, Umeå University6, University of Coimbra7, Royal Bournemouth Hospital8, University of Eastern Piedmont9, Sheba Medical Center10, Lund University11, Valley Hospital12, Charité13, Queen Mary University of London14, Royal Free London NHS Foundation Trust15, Netherlands Cancer Institute16
TL;DR: The CheckMate-9ER trial as discussed by the authors showed an improved progression-free survival (PFS), overall survival (OS), and an objective response rate (ORR) benefit for the combination of lenvatinib plus pembrolizumab over sunitinib.
About: This article is published in European Urology.The article was published on 2021-10-01. It has received 88 citations till now. The article focuses on the topics: Nivolumab & Pembrolizumab.
Citations
More filters
TL;DR: The European Association of Urology (EAU) Renal Cell Carcinoma (RCC) Guideline Panel has prepared evidence-based guidelines and recommendations for the management of RCC as discussed by the authors .
281 citations
TL;DR: Functional enrichment and tumor immune microenvironmental analyses showed that high-risk STSs tend to be immunologically sensitive tumors, and a nomogram was constructed combining clinical characteristics with the risk scores, and it was shown to have credible predictive power.
Abstract: Cuproptosis, a new type of programmed cell death, is involved in the development and progression of malignancies. The study of cuproptosis-associated long non-coding RNAs (lncRNAs) in soft tissue sarcomas (STSs) is however limited. There is also uncertainty regarding the prognostic accuracy of cuproptosis-associated lncRNAs in STSs and their relationship to the tumor immune microenvironment. The aim of this study was to determine the prognostic significance of cuprotosis-associated lncRNAs in STSs and their relationship to the tumor immune microenvironment. Transcriptomic and clinical data from patients with STSs were obtained through The Cancer Genome Atlas (TCGA). Overall, 259 patients were randomly allocated to a training group or a testing group. In the training group, a cuproptosis-associated lncRNA signature was constructed, and the signature was verified in the testing group. On the basis of risk scores and clinical features, we later developed a hybrid nomogram. We also performed functional and tumor immune microenvironment analysis based on the cuproptosis-associated lncRNA signature. A signature of 5 cuproptosis-associated lncRNAs was created. Based on this signature, we categorized STS patients into high-risk and low-risk groups. The study showed that patients at high risk had a worse prognosis than those at low risk. A nomogram was then constructed combining clinical characteristics with the risk scores, and it was shown to have credible predictive power. Functional enrichment and tumor immune microenvironmental analyses showed that high-risk STSs tend to be immunologically sensitive tumors. In our study, we found a cuproptosis-associated lncRNAs signature, which serves as an independent prognostic indicator. Cuproptosis-associated lncRNAs may play a role in the tumor immune microenvironment, which might be a therapeutic target for patients with STSs.
32 citations
TL;DR: In this article , an adjuvant trial with pembrolizumab (a programmed death receptor-1 antibody) for the treatment of high-risk clear cell renal cell carcinoma (ccRCC) after surgery showed that the drug prolonged the period of being cancer free significantly, although whether it prolonged survival remained uncertain.
25 citations
TL;DR: In this article, the characteristics and interaction of bone metastases and their immune microenvironment were systematically discussed, and the relevant research progress of the immunological mechanism of tumor bone metastasis was reviewed.
Abstract: The treatment of bone metastases is a thorny issue. Immunotherapy may be one of the few hopes for patients with unresectable bone metastases. Immune checkpoint inhibitors are the most commonly used immunotherapy drugs currently. In this review, the characteristics and interaction of bone metastases and their immune microenvironment were systematically discussed, and the relevant research progress of the immunological mechanism of tumor bone metastasis was reviewed. On this basis, we expounded the clinical application of immune checkpoint inhibitors for bone metastasis of common tumors, including non-small-cell lung cancer, renal cell carcinoma, prostate cancer, melanoma, and breast cancer. Then, the deficiencies and limitations in current researches were summarized. In-depth basic research on bone metastases and optimization of clinical treatment is needed.
18 citations
TL;DR: It is suggested that targeting the positive feedback loop between histone lactylation and PDGFRβ signaling might provide a promising therapeutic strategy for ccRCC patients.
Abstract: Inactive von Hippel-Lindau (VHL) is linked to metabolic reprogramming and plays pivotal roles in the pathogenesis of clear cell renal cell carcinoma (ccRCC). Here, we identify a previously unknown oncogenic role for inactive VHL in actively triggering histone lactylation to promote ccRCC progression. In patients with ccRCC, inactive VHL positively correlates with the presence of histone lactylation, and high levels of histone lactylation indicates poor patient prognosis. Inactive VHL-triggered histone lactylation contributes to ccRCC progression by activating the transcription of platelet-derived growth factor receptor β (PDGFRβ). In turn, PDGFRβ signaling is shown to stimulate histone lactylation, thereby forming an oncogenic positive feedback loop in ccRCC. Target correction of aberrant histone lactylation represses the growth and metastasis of ccRCC in vivo. More importantly, the combined inhibition of histone lactylation and PDGFRβ significantly reinforces the therapeutic efficacy. This work underscores the importance of histone lactylation in facilitating ccRCC progression and suggests targeting the positive feedback loop between histone lactylation and PDGFRβ signaling might provide a promising therapeutic strategy for ccRCC patients.
16 citations
References
More filters
Memorial Sloan Kettering Cancer Center1, University of Texas MD Anderson Cancer Center2, Harvard University3, Fox Chase Cancer Center4, University of Strasbourg5, Queen Mary University of London6, Aarhus University7, Rabin Medical Center8, Tel Aviv University9, University of British Columbia10, Roswell Park Cancer Institute11, Cancer Research UK12, University of Jena13, Pontifícia Universidade Católica do Rio Grande do Sul14, Niigata University15, Complutense University of Madrid16, Cleveland Clinic17, Bristol-Myers Squibb18, Johns Hopkins University19, Macquarie University20, Université Paris-Saclay21
TL;DR: Overall survival and objective response rates were significantly higher with nivolumab plus ipilimumab than with sunitinib among intermediate‐ and poor‐risk patients with previously untreated advanced renal‐cell carcinoma.
Abstract: Background Nivolumab plus ipilimumab produced objective responses in patients with advanced renal-cell carcinoma in a pilot study. This phase 3 trial compared nivolumab plus ipilimumab with sunitinib for previously untreated clear-cell advanced renal-cell carcinoma. Methods We randomly assigned adults in a 1:1 ratio to receive either nivolumab (3 mg per kilogram of body weight) plus ipilimumab (1 mg per kilogram) intravenously every 3 weeks for four doses, followed by nivolumab (3 mg per kilogram) every 2 weeks, or sunitinib (50 mg) orally once daily for 4 weeks (6-week cycle). The coprimary end points were overall survival (alpha level, 0.04), objective response rate (alpha level, 0.001), and progression-free survival (alpha level, 0.009) among patients with intermediate or poor prognostic risk. Results A total of 1096 patients were assigned to receive nivolumab plus ipilimumab (550 patients) or sunitinib (546 patients); 425 and 422, respectively, had intermediate or poor risk. At a median follo...
2,984 citations
Cleveland Clinic1, Fox Chase Cancer Center2, Ivano-Frankivsk National Medical University3, Queen Mary University of London4, Laval University5, University of Colorado Colorado Springs6, University College Dublin7, University of Tübingen8, Taipei Veterans General Hospital9, Osaka City University10, Merck & Co.11, Georgetown University12
TL;DR: Treatment with pembrolizumab plus axitinib resulted in significantly longer overall survival and progression‐free survival, as well as a higher objective response rate, than treatment with sunitin ib among patients with previously untreated advanced renal‐cell carcinoma.
Abstract: Background The combination of pembrolizumab and axitinib showed antitumor activity in a phase 1b trial involving patients with previously untreated advanced renal-cell carcinoma. Whether pembrolizumab plus axitinib would result in better outcomes than sunitinib in such patients was unclear. Methods In an open-label, phase 3 trial, we randomly assigned 861 patients with previously untreated advanced clear-cell renal-cell carcinoma to receive pembrolizumab (200 mg) intravenously once every 3 weeks plus axitinib (5 mg) orally twice daily (432 patients) or sunitinib (50 mg) orally once daily for the first 4 weeks of each 6-week cycle (429 patients). The primary end points were overall survival and progression-free survival in the intention-to-treat population. The key secondary end point was the objective response rate. All reported results are from the protocol-specified first interim analysis. Results After a median follow-up of 12.8 months, the estimated percentage of patients who were alive at 12 months was 89.9% in the pembrolizumab-axitinib group and 78.3% in the sunitinib group (hazard ratio for death, 0.53; 95% confidence interval [CI], 0.38 to 0.74; P Conclusions Among patients with previously untreated advanced renal-cell carcinoma, treatment with pembrolizumab plus axitinib resulted in significantly longer overall survival and progression-free survival, as well as a higher objective response rate, than treatment with sunitinib. (Funded by Merck Sharp & Dohme; KEYNOTE-426 ClinicalTrials.gov number, NCT02853331.).
2,075 citations
Memorial Sloan Kettering Cancer Center1, Netherlands Cancer Institute2, Cleveland Clinic3, Institut Gustave Roussy4, University of Texas MD Anderson Cancer Center5, University of Glasgow6, University of British Columbia7, University of Lyon8, Osaka University9, University of Ulsan10, Russian Railways11, McGill University12, Medical University of Vienna13, The Royal Marsden NHS Foundation Trust14, Georgetown University15, University of Tübingen16, Pfizer17, Harvard University18
TL;DR: Progression‐free survival was significantly longer with avelumab plus axitinib than with sunit inib among patients who received these agents as first‐line treatment for advanced renal‐cell carcinoma.
Abstract: Background In a single-group, phase 1b trial, avelumab plus axitinib resulted in objective responses in patients with advanced renal-cell carcinoma. This phase 3 trial involving previously...
1,597 citations
Brigham and Women's Hospital1, Queen Mary University of London2, Institut Gustave Roussy3, Universidad Autónoma de Nuevo León4, Washington University in St. Louis5, University of Pavia6, University of Texas MD Anderson Cancer Center7, Royal Brisbane and Women's Hospital8, University of Colorado Denver9, Niigata University10, University of Tübingen11, Bristol-Myers Squibb12, Exelixis13, National Institutes of Health14, Memorial Sloan Kettering Cancer Center15
TL;DR: Nivolumab plus cabozantinib had significant benefits over sunitinib with respect to progression-free survival, overall survival, and likelihood of response in patients with previously untreated advanced renal-cell carcinoma.
Abstract: Background The efficacy and safety of nivolumab plus cabozantinib as compared with those of sunitinib in the treatment of previously untreated advanced renal-cell carcinoma are not known. ...
816 citations
Memorial Sloan Kettering Cancer Center1, Yonsei University2, Royal Free London NHS Foundation Trust3, University of Duisburg-Essen4, Texas Oncology5, Catholic University of Korea6, McMaster University7, University of Miami8, University of Western Ontario9, Autonomous University of Barcelona10, University of Queensland11, Seoul National University12, Macquarie University13, Rambam Health Care Campus14, Kyushu University15, University of Tübingen16, Medical University of Vienna17, Eisai18, Merck & Co.19, Harvard University20
TL;DR: In this article, Lenvatinib in combination with pembrolizumab or everolimus has been shown to have activity against advanced renal cell carcinoma (RCC).
Abstract: Background Lenvatinib in combination with pembrolizumab or everolimus has activity against advanced renal cell carcinoma. The efficacy of these regimens as compared with that of sunitinib ...
722 citations