Villejuif, 5 June 2016

ASCO 2016
Advances in bladder, kidney, testis and prostate cancers

Immunotherapy is being developed in the field of genitourinary cancer.

On Sunday 5th June, Dr. Christophe Massard, Head of the Early Trials Committee in the Drug Development Department (DITEP), will be reporting early encouraging results for a novel immunotherapeutic agent in bladder cancer.

Dr. Bernard Escudier, Oncologist in the Department of Medical Oncology, will be demonstrating the virtues of prolonging immunotherapy in patients with advanced bladder cancer even when the disease has progressed.

Professor Karim Fizazi, Head of the Department of Medical Oncology is the author of two communications. On Sunday 5th June he will present the results of five years of personalised, intensive polychemotherapy in patients with severe testicular cancer (GETUG 13). He is also the Coordinator in France of the FIRSTANA study. In this study a new chemotherapeutic agent is being assessed as a firstline treatment of prostate cancer. These results will be communicated on Monday 6th June.

First evaluation of durvalumab, a novel immunotherape utic agent, in bladder cancer

Bladder cancer is common and has a poor prognosis, especially when it has metastasised. Until very recently, therapeutic options were limited, being largely restricted to the use of various cytotoxic chemotherapeutic drugs such as cisplatin. Now, the new immunotherapeutic drugs are yielding encouraging results. A number of trials have already been conducted at Gustave Roussy using anti-PD-1 or PD-L1 agents such as atezolizumab.

Dr. Christophe Massard, Head of the Early Trials Committee in DITEP and Oncologist on the Genitourinary Committee in the Gustave Roussy Department of Medical Oncology is presenting the first intermediate results of durvalumab’s efficacy and safety profile in patients with inoperable or metastatic bladder cancer in whom conventional treatment has failed. This is a phase I/II multicentre trial. Durvalumab is an anti PD-L1 antibody which reverses inhibition of the immune system induced by binding of the PD-L1 ligand to PD-1 and CD80 T-lymphocyte receptors. 

At the time of analysis of the data, 61 patients recruited to the trial were available for evaluation and 42 were assessed for tumour response. With an objective response rate of 38.1 %, the results of this trial are encouraging. It appears that responsiveness depends on the presence of PDL-L1, as the rate reaches 53.6 % where the tumour or its micro-environment expresses the PD-L1 ligand. This value even rises to 61.1 % when PD-L1 is found only in the tumour micro-environment.

Durvalumab seems to be relatively well tolerated. 64% of the patients had manageable side effects, of which those seen most frequently were fatigue and diarrhoea. The findings in this early trial are the fruit of close collaboration between the two departments at Gustave Roussy led by Dr. Massard.

> Read the abstract: Safety and efficacy of durvalumab (MEDI4736), a PD-L1 antibody, in urothelial bladder cancer.

Prolonging immunotherapy in a selected population when the disease is progressing seems to be associated with an increase in overall survival in patients with advanced kidney cancer

Prolonging immunotherapy in a selected population when the disease is progressing seems to be associated with an increase in overall survival in patients with advanced kidney cancer

On Monday 6th June, Dr. Bernard Escudier, Oncologist specialising in genitourinary tumours in the Department of Medical Oncology at Gustave Roussy, is to present an analysis of the results from the phase III CheckMate 025 study, which aimed to define the role of continued treatment with nivolumab while the disease is progressing (monitored by imaging according to RECIST criteria). This is an important question for those Oncologists who are treating patients with these new agents because it is generally considered that proven disease-progression on RECIST criteria should lead to a change of treatment.

Of the 406 patients with advanced renal cancer treated with nivolumab included in the study, treatment was continued for 38 % of them while 36 % of them stopped it after the disease progressed. The results show that prolongation of treatment seems to increase the objective response rate to a level of 20 % compared with a value of 14 % when the drug is stopped at the stage of disease progression. 14 % of the patients who continued immunotherapy had tumour reduction greater than or equal to 30 % after the first progression. Overall survival is also better at 28.1 months versus 15 months. Thus, continuing to treat despite tumour progression seems to offer benefits for patients, who are probably a selected group.

Nivolumab is an anti-PD-1 antibody. It has been shown to be effective in patients with metastatic renal cancer after two or more anti-angiogenic drugs have failed and it has a benefit in terms of overall survival of more than 5 months when compared with everolimus.

> Read the abstract: Treatment beyond progression with nivolumab (nivo) in patients (pts) with advanced renal cell carcinoma (aRCC) in the phase III CheckMate 025 study.

The prospect of changes in practice with the good 5 year results of the GETUG 13 trial in testicular cancer

GETUG 13 is an international phase III, multicentre comparative trial. It is sponsored by Unicancer and coordinated by Professor Karim Fizazi, Oncologist specialising in genitourinary tumours and Head of the Department of Medical Oncology. In summary, in this study, the risk of tumour progression is reduced by 35 % and that of death by 31 % when patients who have testicular cancer of poor prognosis are treated by so-called “dose-dense” individualised chemotherapy.

The good outcome at 5 years in GETUG 13 ought to lead to more general use of intensive “dosedense” chemotherapy as a new standard treatment in testicular cancer of poor prognosis and in those in whom the rate of fall in blood tumour markers is slow.

> Read the abstract: Mature results of the GETUG 13 phase III trial in poor-prognosis germ-cell tumors (GCT).

Cabazitaxel has not demonstrated its superiority as a firstline treat ment in prostate cancer

Cabazitaxel is indicated as a second-line therapy in patients with metastatic hormoneresistant prostate cancer who have previously received docetaxel-based chemotherapy. It had been shown to be superior to mitoxantrone in the pivotal TROPIC study.

FIRSTANA is an international phase III comparative study, the objective of which is to evaluate the possible role of cabazitaxel as a first-line chemotherapeutic agent.
1168 patients with metastatic prostate cancer resistant to hormone therapy were included in this trial. None of them had received chemotherapy previously. They were randomised to three arms. A course of chemotherapy was administered every 3 weeks: cabazitaxel at a dose of 25 mg/m2 (dosage given in marketing authorisation documentation) or at a dose of 20 mg/m2, or docetaxel 75 mg/m2. All of the patients also received prednisone.

There were no significant differences in overall survival at 2 years with either of the two doses of cabazitaxel and nor was there any reduction in risk of death by comparison with docetaxel. The same conclusion was reached for the other outcomes followed: survival without disease progression, survival without tumour progression, PSA levels, bone involvement, pain and quality of life. Only tumour response was better with cabazitaxel 25 mg/m2 (41.6 % vs 30.9 % for docetaxel), and fewer side effects were seen with cabazitaxel 20 mg/m2.

Although this study has concluded that cabazitaxel as first-line chemotherapy does not benefit patients with hormoneresistant metastatic prostate cancer when compared with docetaxel treatment, the trial has helped to refine knowledge of this chemotherapeutic agent and how best to use it.

FIRSTANA was sponsored by Sanofi and was coordinated in France by Professor Karim Fizazi.

> Read the abstract: Cabazitaxel vs docetaxel in chemotherapy-naive (CN) patients with metastatic castration-resistant prostate cancer (mCRPC): A three-arm phase III study (FIRSTANA).

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