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Company: Bayer / Onyx
Approval Status: FDA Approved December 2005
Specific Treatments: Renal Cell Carcinoma
Drug: Sorafenib



Nexavar (sorafenib) is a multikinase inhibitor targeting a number of serine/threonine and receptor tyrosine kinases. Inhibition of these systems inhibits division and growth of tumor cells, and potentiates cellular apoptosis.

Nexavar is specifically indicated for the treatment of advanced renal cell carcinoma (RCC).

Nexavar is supplied as a orally available tablet; each tablet contains 200 mg of the drug. Recommended dosage is 400 mg (two tablets) twice daily. As necessary, dose may be reduced to 400 mg once daily or once every other day to manage treatment-related toxicity.



FDA Approval

Approval of Nexavar (sorafenib) was supported by both a Phase II and a Phase III clinical trial.

Phase II Study
Nexavar was investigated in a randomized, controlled study designed to investigate the efficacy of the drug; the trial’s primary endpoint was the percentage of patients remaining on-treatment and progression free after 24 weeks. 202 RCC patients received 12 weeks of open label Necavar therapy; following radiological assessment of tumor state, patients experiencing >25% reduction in tumor size continued open label treatment (n=79), and patients with <25% response were randomized to receive the drug or placebo through week 24. Among this subject of patients, Nexavar was seen to significantly increase both the percentage of patients maintianing progression-free survival (PFS) at week 24 (50% vs. 18%; p=0.0077) and the duration of PFS (163 vs. 41 days; p=0.0001), compared to placebo.

Phase III study
Nexavar was also studied in an international, multi-center, randomized, double-blind, placebo-controlled phase III trial, which enrolled 769 RCC patients. Subjects received 400 mg of the drug or placebo twice daily, until evidence of PFS was observed. Trial data demonstrated significant efficacy in prolonging PFS, compared to placebo (167 days vs. 84 days). This corresponded to an estimated hazard ratio (risk of disease progression for Nexavar compared to placebo) of 0.44. Subpopulation analyses indicated comparable efficacy across several tumor demographics, including patients who had not previously received therapy with interferon or IL-2 (PFS: 172 days vs. 85 days). Secondary analysis of tumor response indicated that 2% of patients receiving Nexavar (n=7) experienced partial disease response (>50% reduction in tumor size); no patients receiving placebo experienced this response. Interim overall survival data yielded a risk of death hazard ratio of 0.72 (Nexavar vs. placebo), which did not meet statistical significance.



Adverse events associated with the use of Nexavar (sorafenib may include, but are not limited to, the following:

  • Diarrhea
  • Rash/Desquamation
  • Fatigue
  • Anemia
  • Hand/Foot Skin Reaction
  • Alopecia
  • Nausea
  • Pruritus
  • Anorexia
  • Hemorrhage
  • Sensory Neuropathy

In addition, the dermatologic adverse events, including erythmia, often required dose adujustment when they were grade 2 or higher. Recurrent grade 3 reactions (3 or more instances), including moist desquamation, ulceration, blistering and severe discomfort, may require termination of treatment. Patients are advised to monitor such reactions closely in cooperation with their doctors.



Nexavar is a multikinase inhibitor, with disruptive activity at intracellular CRAF, BRAF and mutant BRAF receptors, and extracellular KIT, FLT-3, VEGFR-2, VEGFR-3 and PDGFR-B receptors. These kinases are involved in multiple systems of angiogenesis and intracellular signalling, and their disruption is thought to inhibit tumor growth.



Staehler M, Rohrmann K, Haseke N, Stief CG, Siebels M. Targeted agents for the treatment of advanced renal cell carcinoma Current Drug Targets 2005 Nov;6(7):835-46

Moore M, Hirte HW, Siu L, Oza A, Hotte SJ, Petrenciuc O, Cihon F, Lathia C, Schwartz B. Phase I study to determine the safety and pharmacokinetics of the novel Raf kinase and VEGFR inhibitor BAY 43-9006, administered for 28 days on/7 days off in patients with advanced, refractory solid tumors Annals of Oncology 2005 Oct;16(10):1688-94

Clark JW, Eder JP, Ryan D, Lathia C, Lenz HJ. Safety and pharmacokinetics of the dual action Raf kinase and vascular endothelial growth factor receptor inhibitor, BAY 43-9006, in patients with advanced, refractory solid tumors Clinical Cancer Research 2005 Aug 1;11(15):5472-80

Ahmad T, Eisen T. Kinase inhibition with BAY 43-9006 in renal cell carcinoma Clinical Cancer Research 2004 Sep 15;10(18 Pt 2):6388S-92S

Source: centerwatch