2013 Genitourinary Cancers Symposium

Professor Eleni Efstathiou from MD Anderson Cancer Center, Houston, Texas, USA, and the University of Athens, Greece, summarises for ecancer.TV the latest study findings presented at the 2013 Genitourinary Cancers Symposium, February 14-16, 2013, Orlando, Florida. Professor Efstathiou notes that the third (planned) interim analysis of the COU-AA-302 study has confirmed the benefits of abiraterone in chemotherapy naive, castration-resistant prostate cancer patients with metastatic disease. As well as an increased radiographic progression-free survival, these latest results show the trend towards overall survival (non-significant). No new safety concerns were raised from this prolonged administration analysis, and Professor Efstathiou outlines the implications of these latest findings to physicians. Professor Efstathiou comments on the negative study results from READY and VENICE trials, and offers an explanation for these results. She also outlines a new study assessing the combination of abiraterone and enzalutamide, and the markers being used to assess efficacy and outcomes in this study. Professor Efstathiou discusses the extensive collaborations between institutions to identify markers of efficacy and disease progression in this current period of considerable drug development. She also advises on what and how physicians should currently be prescribing in clinical practice. In her take-home message to physicians, Professor Efstathiou stresses that mCRPC is largely androgen-dependent castration resistant and that the tumour microenvironment determines how the tumour responds to agents; thereby explaining the opportunities offered by the newer agents targeting androgen signalling before moving on to a chemotherapeutic agent.

Professor Kurt Miller, Head of Urology, Charité Universitätsmedizin, Berlin, Germany, talks to ecancer.TV about the data presented at the 2013 Genitourinary Cancers Symposium on mCRPC. Professor Miller expresses excitement about the wide variety of drugs being explored in mCRPC. He points to the latest results of the AFFIRM study with enzalutamide showing positive quality of life data, and emphasises the importance of quality of life data in this patient group. He also notes the data from the Cougar 301 and Cougar 302 studies with abiraterone acetate. He then outlines the key data from the AFFIRM and Cougar 301 and 302 studies, and outlines the differences between abiraterone and enzalutamide. Professor Miller advises physicians on the use of these two agents (as well as their potential use in combination), and of additional new agents on the horizon. In terms of challenges for physicians treating patients with mCRPC, Professor Miller notes the importance of determining response criteria, progression criteria, choice and order of drug therapies.

Dr Howard Scher, Chief GU Oncology Service, Memorial Sloan Kettering Cancer Center, New York, USA, first addresses for ecancer.TV the debate as to whether we should be calling mCRPC hormone resistant or castration resistant, noting that changes at the molecular level can help clarify this. He then outlines why hormones remain important even in refractory patients by explaining that androgen levels in the blood differ from androgen levels in the tumour. Also, that the tumour learns to make more androgen receptors, so becoming hypersensitive to androgens. This is why abiraterone and enzalutamide appear to work well in these tumours. Dr Scher explains current questions over whether corticosteroids are beneficial or are linked to tumour growth due to findings from the enzalutamide post-hoc analysis, and how patients could be selected for benefits vs. possible harm from corticosteroids. He also comments on the use of corticosteroids in patients taking abiraterone. Dr Scher comments on how abiraterone and enzalutamide have advanced current treatment in patients with mCRPC, and briefly outlines the top-line findings with these agents and when chemotherapy should be used. He emphasises the need to better tailor treatment approaches to the individual patient.

Dr Charles Ryan from the UCSF Cancer Center, San Francisco, California, USA, talks to ecancer.TV about the COU-AA-302 study, being the principal investigator. He explains why the study was set up why the particular patient group was selected and gives an overview of the study. Dr Ryan then summarises the study results, including radiographic progression-free survival, and notes the observed effects in the corticosteroid plus placebo arm. Dr Ryan says that this study shows the abiraterone is now a valid option in chemotherapy-naive patients. He comments on the use of steroids based on the results from the enzalutamide vs. placebo study and the clinical implications of these findings. Dr Ryan also shares his thoughts on the potential combined use of abiraterone and enzalutamide, and on the negative results from the READY and VENICE studies. Dr Ryan comments of the volume of positive data currently being observed in mCRPC and the new agents currently being studied. In his take-home message to physicians, Dr Ryan notes that prostate cancer is a treatable condition, and that intervening early in mCRPC may delay many adverse effects seen from the disease.

Professor Karim Fizazi, Head of the Department of Cancer Medicine at the Institut Gustave Roussy, Villejuif, France, and Full Professor in Oncology, University of Paris, France, talks to ecancer about the hottest results presented at the 2013 Genitourinary Cancers Symposium. Starting with the main studies with a negative outcome, he outlines two large phase III studies; one with aflibercept, and the other with dasatinib. Explaining the negative results of the VENICE study (multinational phase III trial examining the efficacy of aflibercept versus placebo in combination with docetaxel/prednisone for first-line treatment of mCRPC), Professor Fizazi suggests that angiogenesis is not a major factor in prostate cancer. As for the negative results from the READY trial (randomised phase III trial examining overall survival and safety of dasatinib/docetaxel versus docetaxel in patients with metastatic castration-resistant prostate cancer (mCRPC), Professor Fizazi suggests that dasatinib is more a bone-targeting agent than an cancer-targeting agent. Outlining the main positive study results, Professor Fizazi points to the new generation endocrine therapies, such as abiraterone acetate. For this agent, the results of the third interim analysis presented from the COU-AA-302 randomised phase III study of abiraterone acetate in chemotherapy naive patients with mCRPC showed positive results. Also, more results from the AFFIRM study with enzalutamide in patients with more advanced disease, in patients with and without corticosteroids. Professor Fizazi also comments on the use of corticosteroids with abiraterone and enzalutamide. Professor Fizazi shares his views on the use of abiraterone and enzalutamide in patients with mCRPC in terms of when and how they should be used. He comments on toxicity, symptom improvement, overall survival improvement and effects on quality of life of these two newer agents. Finally, Professor Fizazi shares his views on the early results with the new androgen-receptor inhibitors, ODM-201 and ARN-509. These agents add to the physicians’ currently growing armamentarium of agents for mCRPC.

Prof James talks to ecancer at the 2013 ASCO GU symposium about chemo-radiotherapy for bladder cancer. His study found that preservation rather than cystectomy is an option in most older patients and many others. Prof James discusses the results and the implications for practice in the UK and further afield.

Dr Loblaw talks to ecancer about a study led by his colleague Dr Suneil Jain at the 2013 ASCO GU meeting looking at migration of Gleason grade with time in patients under active surveillance. This is the largest re-biopsy cohort, with long-term follow-up, described to date, enabling the first estimates of prostate cancer dedifferentiation in patients on AS. Dedifferentiation rates appear higher in patients with intermediate risk prostate cancer compared with those who are low risk at baseline.

Dr Motzer talks to ecancer at the 2013 ASCO GU symposium. TIVO 1 study shows tivozanib an option for renal cell carcinoma: Overall Survival from Phase III study of tivozanib hydrochloride versus sorafenib in patients with renal cell carcinoma.

Dr Aizer talks to ecancer at the 2013 ASCO GU Symposium about the overtreatment of low risk prostate cancer: incidence in USA, cost, complications and implications for the screening debate.

Dr Gilbert talks to ecancer at the 2013 ASCO GU symposium about prediction of relapse in stage I nonseminomatous germ cell tumors (NSGCT) by CXCL12. Results from the MRC TE08 and TE22 clinical trials showed that patients who need to get chemotherapy can be picked out and those who don't can be spared. CXCL12 intensity is prognostic for relapse independently of VI. This additional prognostic information can identify groups at very low and very high risk of relapse with potential clinical utility.

Dr Tombal talks to ecancer at the 2013 ASCO GU meeting about monotherapy with enzalutamide front line in hormone-naïve prostate cancer. ENZA monotherapy (160 mg) was associated with significant PSA response in nearly all men with hormone-naïve prostate cancer. Endocrine level changes and most common AEs (gynecomastica, fatigue and hot flush) were consistent with potent AR inhibition. Clinical trial information: NCT01302041

Dr Nabid talks to ecancer at the 2013 ASCO GU symposium about a phase III randomized study looking at high-risk prostate cancer treated with pelvic radiotherapy and 36 versus 18 months of androgen blockade.