53IN - Molecular insights and treatment outlook for GU malignancies

Date 29 September 2012
Event ESMO Congress 2012
Session Molecular answers and targets on the horizon for the treatment of GU malignancies
Topics Genitourinary Cancers
Pathology/Molecular Biology
Presenter Joaquim Bellmunt
Authors J. Bellmunt
  • Medical Oncology, University Hospital del Mar-IMIM, Barcelona/ES

Abstract

The use of targeted therapies has significantly improved outcomes for patients with mRCC. At present, in Europe and/or the USA, six/seven targeted agents are approved for first- and second-line treatment of clear cell mRCC: sunitinib, sorafenib, temsirolimus, everolimus, bevacizumab (in combination with interferon) pazopanib and axitinib (in the US). In addition, several new targeted agents, such as axitinib (in EU) and tivozanib, are also currently being filed for the treatment of mRCC after successful results of the phase III trials .New treatment options include targeting new pathways like c-MET or the use of novel more selective inmunotherapies such as the anti-PD1 agent. The novel chemotherapeutic agent Cabazitaxel with activity for CRPC in patients failing docetaxel is now available filling an unmet medical need for these patients.In addition immunotherapy with sipuleucel-T, the androgen biosynthesis inhibitor abiraterone acetate, the radioisotope alpharadin and the anti-androgen MDV3100 have all shown to improve overall survival in randomized phase III studies for patients with mCRPC. Agents such as the dual VEGFr/MET inhibitor cabozantinib, the clusterin inhibitor custirsen and the Src inhibitor dasatinib have shown encouraging results in phase II studies, and phase III results with theses agents are eagerly awaited.Novel immunotherapeutics such as prostate-specific membrane antigen-directed therapy and the anti-cytotoxic T lymphocyte-associated receptor 4 (CTLA4) antibody ipilimumab are also under investigation. Targeted therapy with novel drugs directed at specific molecular pathways opens promising new avenues in urothelial tumors to improve patient outcome. Several phase II/III trials, with focus on bevacizumab, aflibercept, sunitinib, sorafenib, gefitinib, lapatinib and trastuzumab have not clarified any specific role for these therapies. However, the presently accruing trial comparing CG +/- bevazicumab is in its half way to shed light on the role of antiangiogenics in urothelial tumors. Other novel, promising targeted agents, including pazopanib, cetuximab and everolimus has shown limited benefit. Identifying pathways critical for tumorigenesis can provide potential strategies for therapeutic intervention in specific tumor types.

Disclosure

The author has declared no conflicts of interest.