CONTEXT: Until the development of novel targeted agents directed against angiogenesis and tumour growth, few treatment options have been available for the treatment of metastatic renal-cell carcinoma (mRCC). OBJECTIVE: This review discusses current targeted therapies for mRCC and provides consensus statements regarding treatment algorithms. EVIDENCE ACQUISITION: Medical literature was retrieved from PubMed up to April 2011. Additional relevant articles and abstract reviews were included from the bibliographies of the retrieved literature. EVIDENCE SYNTHESIS: Targeted treatment for mRCC can be categorized for the following patient groups: previously untreated patients, those refractory to immunotherapy, and those refractory to vascular endothelial growth factor (VEGF)-targeted therapy. Sunitinib and bevacizumab combined with interferon alpha are generally considered first-line treatment options in patients with favourable or intermediate prognoses. Temsirolimus is considered a first-line treatment option for poor-risk patients. Either sorafenib or sunitinib may be valid second-line treatments for patients who have failed prior cytokine-based therapies. For patients refractory to treatment with VEGF-targeted therapy, everolimus is now recommended. Pazopanib is a new treatment option in the first- and second-line setting (after cytokine failure). Sequential and combination approaches, and the roles of nephrectomy and tumour metastasectomy will also be discussed. CONCLUSIONS: Increasing clinical evidence is clarifying appropriate first- and second-line treatments with targeted agents for patients with mRCC. Based on phase 2 and 3 trials, a sequential approach is most promising, while combination therapy is still investigational. The role of nephrectomy in mRCC is being evaluated in ongoing phase 3 clinical trials.
CONTEXT: Until the development of novel targeted agents directed against angiogenesis and tumour growth, few treatment options have been available for the treatment of metastatic renal-cell carcinoma (mRCC). OBJECTIVE: This review discusses current targeted therapies for mRCC and provides consensus statements regarding treatment algorithms. EVIDENCE ACQUISITION: Medical literature was retrieved from PubMed up to April 2011. Additional relevant articles and abstract reviews were included from the bibliographies of the retrieved literature. EVIDENCE SYNTHESIS: Targeted treatment for mRCC can be categorized for the following patient groups: previously untreated patients, those refractory to immunotherapy, and those refractory to vascular endothelial growth factor (VEGF)-targeted therapy. Sunitinib and bevacizumab combined with interferon alpha are generally considered first-line treatment options in patients with favourable or intermediate prognoses. Temsirolimus is considered a first-line treatment option for poor-risk patients. Either sorafenib or sunitinib may be valid second-line treatments for patients who have failed prior cytokine-based therapies. For patients refractory to treatment with VEGF-targeted therapy, everolimus is now recommended. Pazopanib is a new treatment option in the first- and second-line setting (after cytokine failure). Sequential and combination approaches, and the roles of nephrectomy and tumour metastasectomy will also be discussed. CONCLUSIONS: Increasing clinical evidence is clarifying appropriate first- and second-line treatments with targeted agents for patients with mRCC. Based on phase 2 and 3 trials, a sequential approach is most promising, while combination therapy is still investigational. The role of nephrectomy in mRCC is being evaluated in ongoing phase 3 clinical trials.
Authors: Mas Jewett; A Finelli; C Kollmannsberger; L Wood; L Legere; J Basiuk; C Canil; D Heng; N Reaume; S Tanguay; M Atkins; G Bjarnason; J Dancey; M Evans; N Fleshner; M Haider; A Kapoor; R Uzzo; D Maskens; D Soulieres; G Yousef; N Basappa; N Bendali; P Black; N Blais; I Cagiannos; M Care; R Chow; H Chung; P Czaykowski; D Derosa; K Durrant; S Ellard; G Farquharson; C Filion-Brulotte; J Gingerich; L Godbout; R Grant; W Hamilton; W Kassouf; G Kurban; K Lane; Jb Lattouf; D Lau; M Leveridge; J McCarthy; R Moore; S North; P O'brien; E Pituskin; P Racine; R Rendon; A So; S Sridhar; K Stubbs; Z Su; L Taylor; T Udall; P Venner; W Vogel; S Yap; P Yau; M Cooper; N Giroux; D Miron; D Mosher; K Ross; J Willacy Journal: Can Urol Assoc J Date: 2012-02 Impact factor: 1.862