ESMO E-Learning: New Therapies for Advanced Prostate Cancer
- To review emerging therapies for advanced prostate cancer
- To understand a role and safety profile of immunotherapy, androgen Receptor targeting drugs, novel hormonal therapies, and bone targeting drugs in the management of advanced prostate cancer
- To understand the clinical impact and potentials of results achieved within clinical studies that evaluated novel therapies in patients with advanced prostate cancer
|Title||Duration||Content||CME Points||CME Test|
|New Therapies for Advanced Prostate Cancer||25 min.||84 slides||1||Take Test|
There is no such type of cancer, as prostate, that has benefited from so many breakthroughs in the past two years due to the number of emerging agents against advanced prostate cancer, with demonstrated positive outcomes in phase III clinical trials. Until 2010, docetaxel was the only agent capable of improving survival in patients with metastatic castration-resistant prostate cancer (CRPC). The beginning of this decade has been incredibly rich with six agents displaying positive results in phase III trials (sipuleucel-T, cabazitaxel, denosumab, abiraterone, radium-223, and enzalutamide), while other promising agents including notably orteronel, immune checkpoints inhibitors and cabozantinib are currently under study. Taken together, the incorporation of these agents in the routine management of patients with CRPC is likely to expand their median life expectancy, which was only around one year until the early 2000, to more than 30 months in the near future.
The availability of these agents leads to new challenges. Should we use these agents sequentially or in combination? Can we personalise treatment based on the biology of the individual's disease? How will we develop new active compounds in the context where a half dozen approved agents may confound their potential overall survival effect? And finally can our societies afford the costs? Some of these new agents have already been approved, and prostate cancer is a rare example of such a rich harvest of good news reported at recent oncology meetings and in scientific journals.
The mechanisms of action of these agents are extremely diverse, including endocrine therapies directly or indirectly targeting the androgen Receptor (abiraterone, enzalutamide), chemotherapeutic agents (cabazitaxel), bone-targeting agents (denosumab), radiopharmaceuticals (radium-223) and immunotherapy (sipuleucel-T). But the oncology community expects to see more developments in this story of success.
In terms of bone targeting more news is expected from MET and Src inhibition. Met is a tyrosine kinase expressed by osteoblasts and osteoclasts, and overexpressed by prostate cancer cells. Cabozantinib, a Met and VEGF-R2 inhibitor was recently tested in advanced prostate cancer. Another target for therapy is Src, which is expressed by osteoclasts and by some prostate cancer cells. Dasatinib, a Src inhibitor, is tested in patients with CRPC as a single agent and combined with chemotherapy.
With sipuleucel-T, prostate cancer was the first example in oncology where immunotherapy was demonstrated to prolong overall survival. Two other immune modulating treatments have proven effective in phase II trials and currently are under development in phase III: ipilimumab and prostvac.
Many potential targets have been identified in the recent past and numerous trials are on-going testing novel inhibitors. Let’s mention hormonal drugs under development and which act through CYP 17 inhibition or via dual mechanism (CYP 17/antiandrogen), or belong to the second generation of antiandrogens, or act through androgen-receptor cofactors modulation, or via Chaperones inhibition.
This E-Learning module is an excellent update on novel therapies already available or under development in this rapidly evolved field.
The author has reported participation in the Advisory Board of and as Speaker for Amgen, Astellas, Bayer, BMS, Janssen, Sanofi Aventis, Teva.