PURPOSE: To describe the U.S. Food and Drug Administration (FDA) review and approval of sorafenib (Nexavar; Bayer Pharmaceuticals Corp., Montville, NJ, and Onyx Pharmaceuticals Corp., Emeryville, CA), an oral kinase inhibitor, for the treatment of patients with unresectable hepatocellular carcinoma (HCC). EXPERIMENTAL DESIGN: The FDA independently analyzed an international, double-blind, placebo-controlled trial comparing the effect of best supportive care plus sorafenib or matching placebo on overall survival. Eligible patients had unresectable, biopsy-proven HCC and had not received prior systemic therapy. RESULTS: Among the 602 randomized patients (placebo, 303; sorafenib, 299), baseline characteristics were well balanced, and 97% were Child-Pugh score A. HCC was "advanced" in 70% overall, as defined by extrahepatic metastases or by tumor radiographically visible in venous structures outside the liver. Underlying liver diseases included hepatitis B (18%), hepatitis C (28%), and alcohol-related (26%). The trial was stopped following a prespecified second interim analysis showing a statistically significant survival advantage for sorafenib [median, 10.7 vs 7.9 months; hazard ratio, 0.69 (95% confidence interval, (0.55, 0.87)), p = 0.00058]. Adverse events in sorafenib-treated patients included diarrhea in 55% (grade 3, 10%), hand-foot syndrome in 21% (grade 3, 8%), rash in 19% (grade 3, 1%), and cardiac ischemia or infarction in 2.7% (versus 1.3% for placebo). On sorafenib, treatment-emergent hypertension occurred in 9% of patients (placebo, 4%) and was grade 3 in 4% (placebo, 1%); elevated serum lipase occurred in 40% (placebo, 37%); hypophosphatemia occurred in 35% (placebo, 11%). CONCLUSIONS:Sorafenib is the first systemic therapy to demonstrate a survival benefit in a randomized trial for unresectable HCC and has received FDA approval for this indication.
RCT Entities:
PURPOSE: To describe the U.S. Food and Drug Administration (FDA) review and approval of sorafenib (Nexavar; Bayer Pharmaceuticals Corp., Montville, NJ, and Onyx Pharmaceuticals Corp., Emeryville, CA), an oral kinase inhibitor, for the treatment of patients with unresectable hepatocellular carcinoma (HCC). EXPERIMENTAL DESIGN: The FDA independently analyzed an international, double-blind, placebo-controlled trial comparing the effect of best supportive care plus sorafenib or matching placebo on overall survival. Eligible patients had unresectable, biopsy-proven HCC and had not received prior systemic therapy. RESULTS: Among the 602 randomized patients (placebo, 303; sorafenib, 299), baseline characteristics were well balanced, and 97% were Child-Pugh score A. HCC was "advanced" in 70% overall, as defined by extrahepatic metastases or by tumor radiographically visible in venous structures outside the liver. Underlying liver diseases included hepatitis B (18%), hepatitis C (28%), and alcohol-related (26%). The trial was stopped following a prespecified second interim analysis showing a statistically significant survival advantage for sorafenib [median, 10.7 vs 7.9 months; hazard ratio, 0.69 (95% confidence interval, (0.55, 0.87)), p = 0.00058]. Adverse events in sorafenib-treated patients included diarrhea in 55% (grade 3, 10%), hand-foot syndrome in 21% (grade 3, 8%), rash in 19% (grade 3, 1%), and cardiac ischemia or infarction in 2.7% (versus 1.3% for placebo). On sorafenib, treatment-emergent hypertension occurred in 9% of patients (placebo, 4%) and was grade 3 in 4% (placebo, 1%); elevated serum lipase occurred in 40% (placebo, 37%); hypophosphatemia occurred in 35% (placebo, 11%). CONCLUSIONS:Sorafenib is the first systemic therapy to demonstrate a survival benefit in a randomized trial for unresectable HCC and has received FDA approval for this indication.
Authors: David S Hong; Maria E Cabanillas; Jennifer Wheler; Aung Naing; Apostolia M Tsimberidou; Lei Ye; Naifa L Busaidy; Steven G Waguespack; Mike Hernandez; Adel K El Naggar; Alder K El Naggar; Savita Bidyasar; John Wright; Steven I Sherman; Razelle Kurzrock Journal: J Clin Endocrinol Metab Date: 2011-02-02 Impact factor: 5.958
Authors: Lei Li; Li Che; Kevin M Tharp; Hyo-Min Park; Maria G Pilo; Dan Cao; Antonio Cigliano; Gavinella Latte; Zhong Xu; Silvia Ribback; Frank Dombrowski; Matthias Evert; Gregory J Gores; Andreas Stahl; Diego F Calvisi; Xin Chen Journal: Hepatology Date: 2016-03-25 Impact factor: 17.425
Authors: Melanie B Thomas; Deborah Jaffe; Michael M Choti; Jacques Belghiti; Steven Curley; Yuman Fong; Gregory Gores; Robert Kerlan; Phillipe Merle; Bert O'Neil; Ronnie Poon; Lawrence Schwartz; Joel Tepper; Francis Yao; Daniel Haller; Margaret Mooney; Alan Venook Journal: J Clin Oncol Date: 2010-08-02 Impact factor: 44.544
Authors: David S Hong; Said M Sebti; Robert A Newman; Michelle A Blaskovich; Lei Ye; Robert F Gagel; Stacy Moulder; Jennifer J Wheler; Aung Naing; Nizar M Tannir; Chaan S Ng; Steven I Sherman; Adel K El Naggar; Rabia Khan; Jon Trent; John J Wright; Razelle Kurzrock Journal: Clin Cancer Res Date: 2009-11-10 Impact factor: 12.531