Ana Elena Martín-Aguilar1, Haidé Núñez-López1, Juan C Ramirez-Sandoval2. 1. Centro Médico Nacional Siglo XXI, Av. Cuauhtémoc 330, Doctores, Cuauhtémoc, 06720 Ciudad de México, CDMX, Mexico City, Mexico. 2. Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Vasco de Quiroga 15, Belisario Dominguez Sección XVI, 14080, Mexico City, PC, Mexico. juancarlosramirezsandoval@yahoo.com.
Abstract
BACKGROUND: Sequential inhibition of the vascular endothelial growth factor (VEGF) pathway with sorafenib could be useful for patients with metastatic renal cell carcinoma (RCC). Our aim was to determine the activity and tolerability of sorafenib as a second-line therapy in advanced RCC initially treated with a different VEGF-tyrosine kinase inhibitor (TKI). METHODS: A prospective observational cohort in Mexico (2012-2019). We included 132 subjects with metastatic RCC and who had progression despite treatment with sunitinib. The primary end-point was time to disease progression as evaluated every 12-16 weeks. RESULTS: The mean age of the cohort was 59 years (interquartile range [IQR] 50-72), 96 (73%) were men, and 48 (36%) had a favorable prognosis according to the IMDC (International Metastatic RCC Database Consortium) prognostic model. The median progression-free survival (PFS) and overall-survival after the introduction of sorafenib treatment was 8.6 months (95% confidence interval [CI]: 6.7-10.5) and 40 months (95% CI: 34.5-45.4) respectively. The median overall survival from RCC diagnosis to death was 71 months (95% CI: 58.2-83.8). On multivariable analyses, age > 65 years was associated with a longer PFS (HR 0.51; 95% CI: 0.31-0.86; p = 0.018). The median PFS in subjects aged > 65 years was longer compared to subjects ≤65 years (14.0 [95% CI: 9.2-18.8] vs. 7.2 months [95% CI: 5.3-9.1]; p = 0.012). Adverse events grade ≥ 3 associated with sorafenib occurred in 38 (29%) patients. CONCLUSION: Sequential inhibition of VEGF with sorafenib as a second-line treatment may benefit patients with metastatic RCC, especially in subjects > 65 years old.
BACKGROUND: Sequential inhibition of the vascular endothelial growth factor (VEGF) pathway with sorafenib could be useful for patients with metastatic renal cell carcinoma (RCC). Our aim was to determine the activity and tolerability of sorafenib as a second-line therapy in advanced RCC initially treated with a different VEGF-tyrosine kinase inhibitor (TKI). METHODS: A prospective observational cohort in Mexico (2012-2019). We included 132 subjects with metastatic RCC and who had progression despite treatment with sunitinib. The primary end-point was time to disease progression as evaluated every 12-16 weeks. RESULTS: The mean age of the cohort was 59 years (interquartile range [IQR] 50-72), 96 (73%) were men, and 48 (36%) had a favorable prognosis according to the IMDC (International Metastatic RCC Database Consortium) prognostic model. The median progression-free survival (PFS) and overall-survival after the introduction of sorafenib treatment was 8.6 months (95% confidence interval [CI]: 6.7-10.5) and 40 months (95% CI: 34.5-45.4) respectively. The median overall survival from RCC diagnosis to death was 71 months (95% CI: 58.2-83.8). On multivariable analyses, age > 65 years was associated with a longer PFS (HR 0.51; 95% CI: 0.31-0.86; p = 0.018). The median PFS in subjects aged > 65 years was longer compared to subjects ≤65 years (14.0 [95% CI: 9.2-18.8] vs. 7.2 months [95% CI: 5.3-9.1]; p = 0.012). Adverse events grade ≥ 3 associated with sorafenib occurred in 38 (29%) patients. CONCLUSION: Sequential inhibition of VEGF with sorafenib as a second-line treatment may benefit patients with metastatic RCC, especially in subjects > 65 years old.
Authors: Robert J Motzer; Thomas E Hutson; Hilary Glen; M Dror Michaelson; Ana Molina; Timothy Eisen; Jacek Jassem; Jakub Zolnierek; Jose Pablo Maroto; Begoña Mellado; Bohuslav Melichar; Jiri Tomasek; Alton Kremer; Han-Joo Kim; Karen Wood; Corina Dutcus; James Larkin Journal: Lancet Oncol Date: 2015-10-22 Impact factor: 41.316
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Authors: Robert J Motzer; Bernard Escudier; Stéphane Oudard; Thomas E Hutson; Camillo Porta; Sergio Bracarda; Viktor Grünwald; John A Thompson; Robert A Figlin; Norbert Hollaender; Gladys Urbanowitz; William J Berg; Andrea Kay; David Lebwohl; Alain Ravaud Journal: Lancet Date: 2008-07-22 Impact factor: 79.321
Authors: William K Oh; David McDermott; Camillo Porta; Antonin Levy; Reza Elaidi; Florian Scotte; Robert Hawkins; Daniel Castellano; Joaquim Bellmunt; Sun Young Rha; Jong-Mu Sun; Paul Nathan; Bruce A Feinberg; Jeffrey Scott; Ray McDermott; Jin-Hee Ahn; John Wagstaff; Yen-Hwa Chang; Yen-Chuan Ou; Paul Donnellan; Chao-Yuan Huang; John McCaffrey; Po-Hui Chiang; Cheng-Keng Chuang; Caroline Korves; Maureen P Neary; Jose R Diaz; Faisal Mehmud; Mei Sheng Duh Journal: Int J Oncol Date: 2013-11-15 Impact factor: 5.650