title: Efficacy and safety of sorafenib in patients with advanced renal cell carcinoma with and without prior cytokine therapy, a subanalysis of TARGET.
abstract: Before the development of targeted therapies, administration of cytokines (e.g., interleukin-2, interferon-alpha) was the primary systemic treatment option for advanced renal cell carcinoma. Sorafenib, an oral targeted, multikinase inhibitor, significantly prolonged progression-free survival and overall survival in the Treatment Approaches in Renal Cancer Global Evaluation Trial (TARGET), a large (N = 903) phase III, double-blind, randomised, placebo-controlled study of patients with advanced renal cell carcinoma resistant to standard therapy. This analysis of a patient subgroup from TARGET evaluated the safety and efficacy of sorafenib in patients who had received prior cytokine therapy (sorafenib: n = 374; placebo: n = 368) and in patients who were cytokine-naïve (sorafenib: n = 77; placebo: n = 84). Progression-free survival was significantly prolonged with sorafenib therapy compared with placebo among patients with and without prior cytokine therapy (respectively 5.5 vs. 2.7 months; hazard ratio, 0.54; 95% confidence interval, 0.45-0.64 and 5.8 vs. 2.8 months; hazard ratio, 0.48; 95% confidence interval, 0.32-0.73). Clinical benefit rates for sorafenib-treated patients compared with placebo patients were also higher (cytokine-treated: 83 vs. 54.3%; cytokine-naïve: 85.7 vs. 56.0%). Sorafenib was well tolerated in both subgroups (grade 3/4: 20 and 22%, respectively). Sorafenib demonstrated a consistent, significant clinical benefit against advanced renal cell carcinoma, with a twofold improvement in progression-free survival and disease control rate, with similar toxicities in patients with or without prior cytokine treatment.
authors.affiliation: Centre Leon Berard and Claude Bernard University, 28 Rue Laennec, Lyon, 69008, France. negrier@lyon.fnclcc.fr
authors.forename: S
authors.initials: S
authors.lastname: Negrier
authors.forename: E
authors.initials: E
authors.lastname: Jäger
authors.forename: C
authors.initials: C
authors.lastname: Porta
authors.forename: D
authors.initials: D
authors.lastname: McDermott
authors.forename: M
authors.initials: M
authors.lastname: Moore
authors.forename: J
authors.initials: J
authors.lastname: Bellmunt
authors.forename: S
authors.initials: S
authors.lastname: Anderson
authors.forename: F
authors.initials: F
authors.lastname: Cihon
authors.forename: J
authors.initials: J
authors.lastname: Lewis
authors.forename: B
authors.initials: B
authors.lastname: Escudier
authors.forename: R
authors.initials: R
authors.lastname: Bukowski
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001557:Benzenesulfonates / Q000008:administration & dosage / Q000009:adverse effects; D002292:Carcinoma, Renal Cell / Q000188:drug therapy*; D002318:Cardiovascular Diseases / Q000139:chemically induced; D003967:Diarrhea / Q000139:chemically induced; D018572:Disease-Free Survival; D004311:Double-Blind Method; D005260:Female; D006402:Hematologic Diseases / Q000139:chemically induced; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage / Q000009:adverse effects; D007376:Interleukin-2 / Q000008:administration & dosage / Q000009:adverse effects; D053208:Kaplan-Meier Estimate; D007680:Kidney Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009536:Niacinamide / Q000031:analogs & derivatives; D010671:Phenylurea Compounds; D011372:Progestins / Q000008:administration & dosage / Q000009:adverse effects; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D011725:Pyridines / Q000008:administration & dosage / Q000009:adverse effects; D000077157:Sorafenib; D016896:Treatment Outcome; D014748:Vinca Alkaloids / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D000964:Antimetabolites, Antineoplastic; D001557:Benzenesulfonates; D016898:Interferon-alpha; D007376:Interleukin-2; D010671:Phenylurea Compounds; D011372:Progestins; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D014748:Vinca Alkaloids; D009536:Niacinamide; D000077157:Sorafenib