المؤلفون: McDermott, David F, Huseni, Mahrukh A, Atkins, Michael B, Motzer, Robert J, Rini, Brian I, Escudier, Bernard, Fong, Lawrence, Joseph, Richard W, Pal, Sumanta K, Reeves, James A, Sznol, Mario, Hainsworth, John, Rathmell, W Kimryn, Stadler, Walter M, Hutson, Thomas, Gore, Martin E, Ravaud, Alain, Bracarda, Sergio, Suárez, Cristina, Danielli, Riccardo, Gruenwald, Viktor, Choueiri, Toni K, Nickles, Dorothee, Jhunjhunwala, Suchit, Piault-Louis, Elisabeth, Thobhani, Alpa, Qiu, Jiaheng, Chen, Daniel S, Hegde, Priti S, Schiff, Christina, Fine, Gregg D, Powles, Thomas

المصدر: Nature Medicine. 24(6)

مصطلحات موضوعية: Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Immunology, Kidney Disease, Cancer, Adult, Aged, Aged, 80 and over, Antibodies, Monoclonal, Antibodies, Monoclonal, Humanized, Antineoplastic Combined Chemotherapy Protocols, Bevacizumab, Carcinoma, Renal Cell, Female, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Humans, Kaplan-Meier Estimate, Kidney Neoplasms, Male, Middle Aged, Mutation, Sunitinib, Treatment Outcome, Medical and Health Sciences, Biomedical and clinical sciences, Health sciences

الوصف: We describe results from IMmotion150, a randomized phase 2 study of atezolizumab (anti-PD-L1) alone or combined with bevacizumab (anti-VEGF) versus sunitinib in 305 patients with treatment-naive metastatic renal cell carcinoma. Co-primary endpoints were progression-free survival (PFS) in intent-to-treat and PD-L1+ populations. Intent-to-treat PFS hazard ratios for atezolizumab + bevacizumab or atezolizumab monotherapy versus sunitinib were 1.0 (95% confidence interval (CI), 0.69-1.45) and 1.19 (95% CI, 0.82-1.71), respectively; PD-L1+ PFS hazard ratios were 0.64 (95% CI, 0.38-1.08) and 1.03 (95% CI, 0.63-1.67), respectively. Exploratory biomarker analyses indicated that tumor mutation and neoantigen burden were not associated with PFS. Angiogenesis, T-effector/IFN-γ response, and myeloid inflammatory gene expression signatures were strongly and differentially associated with PFS within and across the treatments. These molecular profiles suggest that prediction of outcomes with anti-VEGF and immunotherapy may be possible and offer mechanistic insights into how blocking VEGF may overcome resistance to immune checkpoint blockade.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/2f77r70pTest

المؤلفون: Motzer, Robert, Alekseev, Boris, Rha, Sun-Young, Porta, Camillo, Eto, Masatoshi, Powles, Thomas, Grünwald, Viktor, Hutson, Thomas E, Kopyltsov, Evgeny, Méndez-Vidal, María J, Kozlov, Vadim, Alyasova, Anna, Hong, Sung-Hoo, Kapoor, Anil, Alonso Gordoa, Teresa, Merchan, Jaime R, Winquist, Eric, Maroto, Pablo, Goh, Jeffrey C, Kim, Miso, Gurney, Howard, Patel, Vijay, Peer, Avivit, Procopio, Giuseppe, Takagi, Toshio, Melichar, Bohuslav, Rolland, Frederic, De Giorgi, Ugo, Wong, Shirley, Bedke, Jens, Schmidinger, Manuela, Dutcus, Corina E, Smith, Alan D, Dutta, Lea, Mody, Kalgi, Perini, Rodolfo F, Xing, Dongyuan, Choueiri, Toni K, Galamaga, Rob

المصدر: ENT and Skull Base Surgery

مصطلحات موضوعية: Adult, Aged, 80 and over, Antibodies, Monoclonal, Humanized, Antineoplastic Agents, Antineoplastic Combined Chemotherapy Protocols, Carcinoma, Renal Cell, Everolimus, Female, Humans, Kidney Neoplasms, Male, Middle Aged, Phenylurea Compounds, Programmed Cell Death 1 Receptor, Progression-Free Survival, Protein Kinase Inhibitors, Quinolines, Sunitinib, Survival Analysis

الوصف: 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 is unclear. METHODS: In this phase 3 trial, we randomly assigned (in a 1:1:1 ratio) patients with advanced renal cell carcinoma and no previous systemic therapy to receive lenvatinib (20 mg orally once daily) plus pembrolizumab (200 mg intravenously once every 3 weeks), lenvatinib (18 mg orally once daily) plus everolimus (5 mg orally once daily), or sunitinib (50 mg orally once daily, alternating 4 weeks receiving treatment and 2 weeks without treatment). The primary end point was progression-free survival, as assessed by an independent review committee in accordance with Response Evaluation Criteria in Solid Tumors, version 1.1. Overall survival and safety were also evaluated. RESULTS: A total of 1069 patients were randomly assigned to receive lenvatinib plus pembrolizumab (355 patients), lenvatinib plus everolimus (357), or sunitinib (357). Progression-free survival was longer with lenvatinib plus pembrolizumab than with sunitinib (median, 23.9 vs. 9.2 months; hazard ratio for disease progression or death, 0.39; 95% confidence interval [CI], 0.32 to 0.49; P CONCLUSIONS: Lenvatinib plus pembrolizumab was associated with significantly longer progression-free survival and overall survival than sunitinib. (Funded by Eisai and Merck Sharp and Dohme; CLEAR ClinicalTrials.gov number, NCT02811861.).

العلاقة: https://scholar.barrowneuro.org/ent-and-skull-base-surgery/23Test

الإتاحة: https://doi.org/10.1056/NEJMoa2035716Test
https://scholar.barrowneuro.org/ent-and-skull-base-surgery/23Test

المؤلفون: Choueiri, Toni K., Escudier, Bernard, Powles, Thomas, Tannir, Nizar M., Mainwaring, Paul N., Rini, Brian I., Hammers, Hans J., Donskov, Frede, Roth, Bruce J., Peltola, Katriina, Lee, Jae Lyun, Heng, Daniel Y. C., Schmidinger, Manuela, Agarwal, Neeraj, Sternberg, Cora N., McDermott, David F., Aftab, Dana T., Hessel, Colin, Old, Christian Scheff, Schwab, Gisela, Hutson, Thomas E., Pal, Sumanta, Motzer, Robert J., METEOR Investigators

المساهمون: Department of Oncology, Clinicum

المصدر: Translational Andrology and Urology
Choueiri, T K, Escudier, B, Powles, T, Tannir, N M, Mainwaring, P N, Rini, B I, Hammers, H J, Donskov, F, Roth, B J, Peltola, K, Lee, J L, Heng, D Y C, Schmidinger, M, Agarwal, N, Sternberg, C N, McDermott, D F, Aftab, D T, Hessel, C, Scheffold, C, Schwab, G, Hutson, T E, Pal, S, Motzer, R J & METEOR Investigators 2016, ' Cabozantinib versus everolimus in advanced renal cell carcinoma (METEOR): final results from a randomised, open-label, phase 3 trial ', The Lancet Oncology, vol. 17, no. 7, pp. 917-27 . https://doi.org/10.1016/S1470-2045Test(16)30107-3

مصطلحات موضوعية: Male, 0301 basic medicine, Pyridines, law.invention, chemistry.chemical_compound, TARGETED THERAPY, PROGNOSTIC-FACTORS, 0302 clinical medicine, Randomized controlled trial, law, Antineoplastic Combined Chemotherapy Protocols, Clinical endpoint, Anilides, Hazard ratio, Middle Aged, Prognosis, CANCER, Kidney Neoplasms, 3. Good health, Survival Rate, Editorial, Oncology, 030220 oncology & carcinogenesis, SURVIVAL, Female, medicine.drug, Sorafenib, medicine.medical_specialty, Cabozantinib, 3122 Cancers, Urology, 03 medical and health sciences, medicine, Humans, Everolimus, COMBINATION, Carcinoma, Renal Cell, Survival rate, Aged, Neoplasm Staging, III TRIAL, business.industry, EAU GUIDELINES, EFFICACY, Interim analysis, Surgery, SORAFENIB, 030104 developmental biology, chemistry, METASTASIS, business, Follow-Up Studies

الوصف: BACKGROUND: Cabozantinib is an oral inhibitor of tyrosine kinases including MET, VEGFR, and AXL. The randomised phase 3 METEOR trial compared the efficacy and safety of cabozantinib versus the mTOR inhibitor everolimus in patients with advanced renal cell carcinoma who progressed after previous VEGFR tyrosine-kinase inhibitor treatment. Here, we report the final overall survival results from this study based on an unplanned second interim analysis. METHODS: In this open-label, randomised phase 3 trial, we randomly assigned (1:1) patients aged 18 years and older with advanced or metastatic clear-cell renal cell carcinoma, measurable disease, and previous treatment with one or more VEGFR tyrosine-kinase inhibitors to receive 60 mg cabozantinib once a day or 10 mg everolimus once a day. Randomisation was done with an interactive voice and web response system. Stratification factors were Memorial Sloan Kettering Cancer Center risk group and the number of previous treatments with VEGFR tyrosine-kinase inhibitors. The primary endpoint was progression-free survival as assessed by an independent radiology review committee in the first 375 randomly assigned patients and has been previously reported. Secondary endpoints were overall survival and objective response in all randomly assigned patients assessed by intention-to-treat. Safety was assessed per protocol in all patients who received at least one dose of study drug. The study is closed for enrolment but treatment and follow-up of patients is ongoing for long-term safety evaluation. This trial is registered with ClinicalTrials.gov, number NCT01865747. FINDINGS: Between Aug 8, 2013, and Nov 24, 2014, 658 patients were randomly assigned to receive cabozantinib (n=330) or everolimus (n=328). The median duration of follow-up for overall survival and safety was 18·7 months (IQR 16·1-21·1) in the cabozantinib group and 18·8 months (16·0-21·2) in the everolimus group. Median overall survival was 21·4 months (95% CI 18·7-not estimable) with cabozantinib and 16·5 months (14·7-18·8) with everolimus (hazard ratio [HR] 0·66 [95% CI 0·53-0·83]; p=0·00026). Cabozantinib treatment also resulted in improved progression-free survival (HR 0·51 [95% CI 0·41-0·62]; p

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e4bc4d936baaba5695527e426e9f6234Test
https://doi.org/10.1016/s1470-2045Test(16)30107-3

المؤلفون: Choueiri, Toni K, Escudier, Bernard, Powles, Thomas, Mainwaring, Paul N, Rini, Brian I, Donskov, Frede, Hammers, Hans, Hutson, Thomas E, Lee, Jae-Lyun, Peltola, Katriina, Roth, Bruce J, Bjarnason, Georg A, Géczi, Lajos, Keam, Bhumsuk, Maroto, Pablo, Heng, Daniel Y C, Schmidinger, Manuela, Kantoff, Philip W, Borgman-Hagey, Anne, Hessel, Colin, Scheffold, Christian, Schwab, Gisela M, Tannir, Nizar M, Motzer, Robert J, Schöffski, Patrick

مصطلحات موضوعية: Adult, Aged, 80 and over, Anilides, Antineoplastic Agents, Carcinoma, Renal Cell, Disease-Free Survival, Everolimus, Female, Humans, Kidney Neoplasms, Male, Middle Aged, Pyridines, Quality of Life, Sirolimus, Survival Analysis

الوصف: Cabozantinib is an oral, small-molecule tyrosine kinase inhibitor that targets vascular endothelial growth factor receptor (VEGFR) as well as MET and AXL, each of which has been implicated in the pathobiology of metastatic renal-cell carcinoma or in the development of resistance to antiangiogenic drugs. This randomized, open-label, phase 3 trial evaluated the efficacy of cabozantinib, as compared with everolimus, in patients with renal-cell carcinoma that had progressed after VEGFR-targeted therapy. ; status: published

وصف الملف: 545699 bytes; application/pdf

العلاقة: New England Journal of Medicine vol:373 issue:19 pages:1814-23; https://lirias.kuleuven.be/handle/123456789/540820Test; https://lirias.kuleuven.be/bitstream/123456789/540820/1//Cabozantinib+versus+Everolimus+in+Advanced+Renal-Cell+Carcinoma.pdfTest

الإتاحة: https://lirias.kuleuven.be/handle/123456789/540820Test
https://lirias.kuleuven.be/bitstream/123456789/540820/1//Cabozantinib+versus+Everolimus+in+Advanced+Renal-Cell+Carcinoma.pdfTest

المؤلفون: Hutson, Thomas E., Davis, Ian D., Machiels, Jean-Pascal, De Souza, Paul L., Rottey, Sylvie, Hong, Bao-Fa, Epstein, Richard J, Baker, Katherine L, McCann, Lauren, Crofts, Theresa, Pandite, Lini, Figlin, Robert A

المساهمون: UCL - SSS/IREC/MIRO - Pôle d'imagerie moléculaire, radiothérapie et oncologie, UCL - (SLuc) Unité d'oncologie médicale

المصدر: Journal of Clinical Oncology, Vol. 28, no. 3, p. 475-480 (2010)

مصطلحات موضوعية: Treatment Outcome, Sulfonamides, Pyrimidines, Middle Aged, Male, Kidney Neoplasms, Humans, Female, Carcinoma, Renal Cell, Antineoplastic Agents, Angiogenesis Inhibitors, Aged, 80 and over, Adult

الوصف: PURPOSE: Inactivation of the von Hippel-Lindau gene in clear-cell renal cell carcinomas (RCC) leads to overexpression of hypoxia inducible factor, a transcription factor regulating vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) gene expression. Pazopanib, an angiogenesis inhibitor targeting VEGF receptor, PDGF receptor, and c-KIT, was evaluated in patients with RCC. PATIENTS AND METHODS: This phase II study was designed as a randomized discontinuation study but was revised to an open-label study on the recommendation of the data monitoring committee (based on week 12 response rate [RR] of 38% in the first 60 patients). The primary end point was changed from progressive disease rate at 16 weeks postrandomization to RR. Pazopanib 800 mg was administered orally once daily. Pazopanib 800 mg was administered orally once daily. RESULTS: The study enrolled 225 patients with metastatic RCC; 155 patients (69%) were treatment naïve, and 70 patients (31%) had received one prior cytokine- or bevacizumab-containing regimen. Overall RR was 35%; median duration of response was 68 weeks. Median progression-free survival (PFS) was 52 weeks. Eastern Cooperative Oncology Group performance status of 0 and time from diagnosis to treatment of more than 1 year were correlated with prolonged PFS. Pazopanib was generally well tolerated. The most common adverse events were diarrhea, fatigue, and hair depigmentation. The most common laboratory abnormalities were elevated AST and ALT. CONCLUSION: Pazopanib demonstrated durable activity in patients with advanced RCC and was generally well tolerated in this population. These findings support the further development of pazopanib in advanced RCC.

العلاقة: boreal:28890; http://hdl.handle.net/2078.1/28890Test; info:pmid/20008644; urn:ISSN:0732-183X; urn:EISSN:1527-7755

الإتاحة: https://doi.org/10.1200/JCO.2008.21.6994Test
http://hdl.handle.net/2078.1/28890Test