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Summary Background In 2013, the interim analysis of the Protocol for Herceptin as Adjuvant therapy with Reduced Exposure (PHARE) trial could not show that 6 months of adjuvant trastuzumab was non-inferior to 12 months. Here, we report the planned final analysis based on the prespecified number of occurring events. Methods PHARE is an open-label, phase 3, non-inferiority randomised trial of patients with HER2-positive early breast cancer comparing 6 months versus 12 months of trastuzumab treatment concomitant with or following standard neoadjuvant or adjuvant chemotherapy. The study was undertaken in 156 centres in France. Eligible patients were women aged 18 years or older with non-metastatic, operable, histologically confirmed adenocarcinoma of the breast and either positive axillary nodes or negative axillary nodes but a tumour of at least 10 mm. Participants must have received at least four cycles of a chemotherapy for this breast cancer and have started receiving adjuvant trastuzumab-treatment. Eligible patients were randomly assigned to either 6 months or 12 months of trastuzumab therapy duration between the third and sixth months of adjuvant trastuzumab. The randomisation was stratified by concomitant or sequential treatment with chemotherapy, oestrogen receptor status, and centre. The primary objective was non-inferiority in the intention-to-treat population in the 6-month group in terms of disease-free survival with a prespecified hazard margin of 1·15. This trial is registered with ClinicalTrials.gov, number NCT00381901. Findings 3384 patients were enrolled and randomly assigned to either 12 months (n=1691) or 6 months (n=1693) of adjuvant trastuzumab. One patient in the 12-month group and three patients in the 6-month group were excluded, so 1690 patients in each group were included in the intention-to-treat analysis. At a median follow-up of 7·5 years (IQR 5·3–8·8), 704 events relevant to disease-free survival were observed (345 [20·4%] in the 12-month group and 359 [21·2%] in the 6-month group). The adjusted hazard ratio for disease-free survival in the 12-month group versus the 6-month group was 1·08 (95% CI 0·93–1·25; p=0·39). The non-inferiority margin was included in the 95% CI. No differences in effects pertaining to trastuzumab duration were found in any of the subgroups. After the completion of trastuzumab treatment, rare adverse events occurred over time and the safety analysis remained similar to the previously published report. In particular, we found no change in the cardiac safety comparison, and only three additional cases in which the left ventricular ejection fraction decreased to less than 50% have been reported in the 12-month group. Interpretation The PHARE study did not show the non-inferiority of 6 months versus 12 months of adjuvant trastuzumab. Hence, adjuvant trastuzumab standard duration should remain 12 months. Funding The French National Cancer Institute.

Background Neoadjuvant cisplatin-based chemotherapy (NAC) is the standard of care in non-metastatic muscle-invasive bladder cancer (MIBC). However, 60-75% patients have residual tumor after neoadjuvant cisplatin-gemcitabin or ddMVAC regimen. Pathological complete response (pCR) after NAC is correlated with overall survival (OS). Based on the overall response rate observed in the metastatic setting, ddMVAC is the most commonly used NAC regimen in Europe in urothelial carcinoma (UC) in fit patients. The emergence of immune checkpoint inhibitor (ICI) in the metastatic setting raises the question if the combination chemo plus ICI could increase the pCR rate. Trial design NEMIO is a French open-label randomized phase II trial assessing in the neoadjuvant setting the combination ddMVAC plus durvalumab (D) alone or in combination with tremelimumab (T): 4 cycles of ddMVAC every 2 weeks + 2 cycles of D (1500 mg) +/- T (75 mg) every 4 weeks. Cystectomy is performed 4-8 weeks after the last dose of ddMVAC. As no safety data are available on the ICI plus ddMVAC combination, 6 pts will be included in each arm in a safety run-in cohort to evaluate the toxicity rate of the 2 regimens. Each arm will be expanded to a maximum of 60 pts according to a Bayesian stopping rule based on grade 3/4 treatment-related adverse events (G 3/4 TRAE). The primary endpoint of the safety run-in phase will be the rate of G3/4 TRAE. The primary endpoint of the phase II will be the pCR rate and G3/4 TRAE. We hypothesized that pCR after ddMVAC + D +/- T will be > or = 45%. Exploratory endpoints will include biomarkers of response and resistance to the combo. Molecular analysis will be conducted on tumor, blood (ctDNA) and urine samples (uDNA). Immunological and metabolomics profile will also be analyzed. Seven patients have yet been enrolled since December 2018 from the 10 French participating centers and we expect the recruitment to be completed in 2021. Clinical trial identification NCT03549715. Legal entity responsible for the study Association pour la Recherche de Therapeutiques Innovantes en Cancerologie (ARTIC). Funding AstraZeneca. Disclosure C. Thibault: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: AstraZeneca; Honoraria (self), Advisory / Consultancy: BMS; Travel / Accommodation / Expenses: Roche; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Sanofi; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Janssen; Honoraria (self), Advisory / Consultancy: Astellas; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Pfizer. D. Borchiellini: Advisory / Consultancy, Research grant / Funding (institution): Roche; Advisory / Consultancy, Research grant / Funding (institution): MSD; Advisory / Consultancy: BMS; Advisory / Consultancy: Pfizer; Advisory / Consultancy, Research grant / Funding (institution): Janssen; Advisory / Consultancy, Research grant / Funding (institution): Astellas; Advisory / Consultancy: Sanofi; Advisory / Consultancy: Ipsen. O. Huillard: Honoraria (self): AstraZeneca; Honoraria (self): BMS; Honoraria (self): Janssen. P. Barthelemy: Advisory / Consultancy: BMS; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Roche; Advisory / Consultancy: Janssen; Advisory / Consultancy: MSD; Advisory / Consultancy: Ipsen; Advisory / Consultancy: Novartis; Advisory / Consultancy: Sanofi. D. Pouessel: Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: AstraZeneca; Advisory / Consultancy, Travel / Accommodation / Expenses: Pfizer; Advisory / Consultancy, Research grant / Funding (institution): Janssen; Research grant / Funding (institution): MSD; Research grant / Funding (institution): Roche; Research grant / Funding (institution): Incyte. A. Flechon: Advisory / Consultancy: BMS; Advisory / Consultancy: Pfizer; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Roche; Advisory / Consultancy: MSD. H. Blons: Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Boehringer; Advisory / Consultancy: MSD. S. Oudard: Honoraria (self): BMS; Honoraria (self): MSD; Honoraria (self): AstraZeneca; Honoraria (self): Roche. All other authors have declared no conflicts of interest.

Background Microsatellite instability-high (MSI-H) is observed in a large variety of cancer types. Immune checkpoint targeted therapies against PD-1 and CTLA-4 have demonstrated significant activity in metastatic colorectal cancer (mCRC) with nivolumab +/- ipilimumab. We aimed to demonstrate a clinical benefit of nivolumab in non-CRC MSI patients. Methods The AcSe immunotherapy program launched by the French National Cancer Institute (INCa) and sponsored by the French network of comprehensive cancer centers (Unicancer) is a nationwide exploratory program which has allowed access to anti-PD-1 therapies outside of their current approvals. A phase II, single arm, AcSe-nivolumab trial has been conducted to investigate the efficacy and tolerance of nivolumab in patients with metastastic/refractory rare tumor types. Here we report the results of the MSI cohort. Nivolumab (240 mg IV) was administered q2w for a max of 2 years or until disease progression (PD), or toxicity. The primary endpoint was the objective response rate (ORR) assessed by RECIST v1.1 at 12 weeks. Results From July 2017 to October 2018, 50 pts (mean age 63 years) were included. Primary locations were endometrial adenoCa (17), gastric (10), small bowel (7), pancreas (5), biliary (4), urothelial (2), ovary (2), and breast (2). 15 patients (30%) had a Lynch syndrome. All patients were pre-treated (mean of previous lines: 1.6) and had a MSI status locally determined by IHC and/or PCR (IHC 15 pts, PCR 4, both 31). The mean number of cycles/patients was 12.9. The ORR at 12 weeks was 38% (95%CI 24.6 to 52.8) and the best ORR at any time was 42% (95%CI, 28.2 to 56.8) with median time to response of 14 weeks. CR: n = 2; PR: n = 17; SD: n = 16; DCR=74%. Median PFS was not reached with a 6-mo PFS at 58.9% (95%CI, 46.5 to 74.6). At the date of analysis, 15 patients died (PD 13, drug related death 1, other 1), with a 6-mo OS rate at 80.3% (95%CI, 69.5 to 92.8). No unexpected adverse event of nivolumab has been observed. Conclusions Nivolumab as monotherapy is highly active in non-colorectal MSI patients, outperforming results of classical chemotherapy in this heavily pre-treated population. Clinical trial identification NCT03012581, EudraCT 2016-002257-37. Legal entity responsible for the study RD Honoraria (institution), Travel / Accommodation / Expenses: MSD; Advisory / Consultancy: Roche; Honoraria (self), Advisory / Consultancy: Sanofi; Honoraria (institution), Travel / Accommodation / Expenses: BMS. E. Saada-Bouzid: Advisory / Consultancy: BMS; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Merck Serono. D. Pouessel: Advisory / Consultancy, Travel / Accommodation / Expenses: AstraZeneca; Advisory / Consultancy: Sanofi; Advisory / Consultancy, Travel / Accommodation / Expenses: Pfizer; Advisory / Consultancy: Astellas; Advisory / Consultancy, Research grant / Funding (institution): Janssen; Research grant / Funding (institution): MSD; Research grant / Funding (institution): Roche; Research grant / Funding (institution): Incyte; Research grant / Funding (institution): A2; Speaker Bureau / Expert testimony: Ipsen; Speaker Bureau / Expert testimony: BMS. C. Le Tourneau: Advisory / Consultancy: MSD; Advisory / Consultancy: BMS; Advisory / Consultancy: Merck Serono; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Nanobiotix; Advisory / Consultancy: Roche; Advisory / Consultancy: Amgen; Advisory / Consultancy: GSK. P. Augereau: Advisory / Consultancy: Pfizer; Advisory / Consultancy: AstraZeneca. J. Soria: Advisory / Consultancy, Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca; Shareholder / Stockholder / Stock options: Gritstone; Advisory / Consultancy: Astex; Advisory / Consultancy: Clovis; Advisory / Consultancy: GSK; Advisory / Consultancy: GammaMabs; Advisory / Consultancy: Lilly; Advisory / Consultancy: MSD; Advisory / Consultancy: Mission Therapeutics; Advisory / Consultancy: Merus; Advisory / Consultancy: Pfizer; Advisory / Consultancy: PharmaMar; Advisory / Consultancy: Pierre Fabre; Advisory / Consultancy: Roche/Genentech; Advisory / Consultancy: Sanofi; Advisory / Consultancy: Servier; Advisory / Consultancy: Symphogen; Advisory / Consultancy: Takeda. A. Marabelle: Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self): BMS; Research grant / Funding (self): Boehringer Ingelheim; Research grant / Funding (self): Fondation MSD Avenir; Advisory / Consultancy: Oncovir; Advisory / Consultancy, Speaker Bureau / Expert testimony: Merck Serono; Advisory / Consultancy: eTheRNA; Advisory / Consultancy, Research grant / Funding (self): Lytix pharma; Advisory / Consultancy: Kyowa Kirin Pharma; Advisory / Consultancy: Novartis, Seattle Genetics, Molecular Partners; Advisory / Consultancy: Symphogen, Bayer, Partner Therapeutics; Advisory / Consultancy: Genmab, RedX pharma, OSE Immunotherapeutics; Advisory / Consultancy, Speaker Bureau / Expert testimony: Amgen, Sanofi, Servier; Advisory / Consultancy: Biothera, Gritstone; Advisory / Consultancy: Nektar, Pierre Fabre; Advisory / Consultancy: GSK; Advisory / Consultancy: Oncosec; Advisory / Consultancy, Research grant / Funding (self): Pfizer; Speaker Bureau / Expert testimony, Research grant / Funding (self): MSD; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self): AstraZeneca/MedImmune; Speaker Bureau / Expert testimony, Research grant / Funding (self): Roche/Genentech. All other authors have declared no conflicts of interest.

Resume Au cours des dernieres annees, la meilleure comprehension des mecanismes de resistance a la castration developpes par la cellule cancereuse prostatique a permis l’emergence de nouvelles classes d’hormonotherapie. Un premier antagoniste de LHRH, le degarelix, a obtenu une AMM dans le cancer de la prostate avance sensible a la castration. Plus recemment, l’acetate d’abiraterone, un inhibiteur du cytochrome CYP17, a montre une augmentation de la survie globale des patients metastatiques en phase refractaire a la castration apres docetaxel. Avant chimiotherapie, cette molecule conduit, dans des resultats precoces, a une augmentation de la survie sans progression radiologique. Une tendance au gain de survie globale semble se dessiner. Enfin, l’enzalutamide (MDV3100), antiandrogene de nouvelle generation, a egalement conduit a un benefice de survie des patients metastatiques pretraites par docetaxel. L’evaluation de ces nouveaux medicaments se poursuit a des stades plus precoces, ainsi que le developpement d’autres molecules des memes classes therapeutiques.

Les effets secondaires de la deprivation androgenique sont de mieux en mieux connus. A cote des bouffees de chaleur et de la dysfonction erectile, les complications cardiovasculaires et osseuses doivent etre prises en compte a la fois dans les indications des medicaments mais aussi dans la surveillance du traitement. L’induction d’un diabete peut etre un evenement precoce, survenant dans les six mois apres le debut du traitement. Les dyslipidemies sont plus rares. L’augmentation de la frequence des accidents cardiovasculaires ou de la mortalite cardiaque reste discutee. Il est maintenant bien demontre que la deprivation androgenique augmente de maniere moderee le risque d’evenements osseux de type osteoporotique. Cette meilleure connaissance des effets secondaires necessite la realisation d’un bilan clinique et paraclinique initial et lors de la surveillance d’une hormonotherapie prolongee.

Les connaissances acquises au cours de la derniere decennie ont permis de demontrer que le cancer de la prostate resistant a la castration (CPRC) demeure sensible aux traitements qui ciblent le recepteur aux androgenes (RA) et ses ligands. La synthese intracrine d’androgenes et l’augmentation d’expression du RA sont les principaux mecanismes qui participent a la croissance tumorale du CPRC. L’acetate d’abiraterone (AA) est un inhibiteur selectif du cytochrome P450 c17 (CYP17), une enzyme capitale intervenant dans la synthese des androgenes. Une etude de phase III a permis de demontrer un gain de survie chez les patients en echec d’une chimiotherapie prealable par docetaxel. Des resultats prometteurs ont ete obtenus dans une phase II avec le MDV3100, un antiandrogene de deuxieme generation, dont l’affinite pour le RA est plus grande que le bicalutamide, et qui limite sa translocation nucleaire, sa fixation sur l’ADN et le recrutement des coactivateurs de la transcription. Les etudes ulterieures devront determiner les sequences optimales d’utilisation de ces molecules, les possibilites d’association, ainsi que leur integration optimale parmi les nouveaux traitements emergents.

Background In the evolution of metastatic castration-resistant prostate cancer (mCRPC), patients present visceral metastases with or without neuroendocrine differentiation in 20% of cases. Patients and methods We assessed the efficacy and toxicity of a platinum-based chemotherapy regimen in mCRPC patients with either neuroendocrine differentiation defined by high serum levels of chromogranin A (CgA) and neuron-specific enolase (NSE) or visceral metastases. Patients received the combination of carboplatin and etoposide every 3 weeks. Efficacy end points included prostate-specific antigen (PSA) and neuroendocrine marker response, objective response and toxicity. Results Of the 60 patients included from April 2005 to January 2008, 78.6% had bone metastases, 46.4% had lymph node involvement and 57.1% had liver and/or lung localizations. The objective response rate was 8.9% in the 46 patients with measurable disease. A neuroendocrine response was observed in 31% of cases for NSE and 7% for CgA. The PSA response rate was 8%. The most common grade 3–4 treatment-related toxic effects were neutropenia (65.5%), thrombocytopenia (32.7%) and anemia (27.3%). There was 7.2% febrile neutropenia, with one toxicity-related death. The median follow-up was 9.3 months [95% confidence interval (CI) 0.2–27.1] and the median overall survival 9.6 months (95% CI 8.7–12.7). Conclusion The benefit–risk ratio of this regimen seems unfavorable due to poor response and high toxicity.

Radical cystectomy with bilateral pelvic lymph node dissection is the standard of care for patients with muscle-invasive bladder cancer, with 5-year survival rates not exceeding 60%. Consequently a multidisciplinary approach including perioperative chemotherapy and/or radiation therapy is required to improve these results. Data from clinical trials and meta-analyses with neoadjuvant chemotherapy have shown a significant benefit in overall survival, with a 5% absolute benefit at five years, provided cisplatin-based combination chemotherapy is used. Reported trials do not support the routine use of adjuvant chemotherapy. The current role of radiation therapy is limited to highly selected cases with a combination of external radiotherapy, partial cystectomy and interstitial brachytherapy.

Le cancer du rein localement avance ou metastatique a longtemps representeun difficile defi therapeutique en oncologie. Encore recemment, la prise en charge reposait sur l’immunotherapie mais conduisait rapidement a une impasse therapeutique. Les nouvelles therapies ciblant le vascular endothelial growth factor (VEGF) ou son recepteur (VEGF-R): sorafenib, sunitinib et bevacizumab ou mTOR (mammalian target of rapamycin): temsirolimus et everolimus ont transforme le pronostic et la qualite de vie de ces patients en quelques annees. La survie globale mediane rapportee dans certains essais est de 26 mois contre 10 a 12 mois a l’ere de l’immunotherapie. Les essais prospectifs randomises validant l’efficacite de ces medicaments permettent de bâtir, en 2009, un algorithme decisionnel afin de proposer aux patients une prise en charge optimale. Toutefois, certaines situations particulieres (metastases cerebrales, histologies papillaires ou chromophobes, patients âges, etc.) n’ont pas ou peu ete evaluees avec ces molecules, et le bien-fonde de leur prescription est alors en question. Leur tolerance et leur impact therapeutique seront etudies dans de futurs essais cliniques.

Postorchidectomy management of stage I testis seminoma has evolved for many years. Three treatment options should be discussed after surgery. Surveillance tends toward taking a more significant place to avoid overtreatment, adjuvant chemotherapy with carboplatin has demonstrated its efficiency, and for some, preventive radiotherapy, the historical reference treatment, is losing momentum. Whatever the chosen orientation, long-term prognosis is excellent with overall survival closed to 100%. In this context, this review underlines the advantages and the drawbacks of the three attitudes but also the unknowns relative to each. Indeed, their knowledge is crucial for informing clearly and with an objective way. Without gold-standard, but with three therapeutic options available, informing our patients is the key so they make an informed choice in dialogue with the oncologist.

Les objectifs de ce reseau sont la mise en place d’une coordination nationale de prise en charge des tumeurs rares du rein de l’adulte. Cette unite s’est constituee autour de deux reunions de concertation pluridisciplinaire (RCP) regionales, l’une sur l’Ile-de-France et l’autre sur le Grand-Sud de facon a recenser, enregistrer et evaluer les traitements proposes a ces patients. L’objectif est de rediger un referentiel pour les tumeurs rares renales elaborees de facon multidisciplinaire afin de definir les modalites de diagnostic, de traitement et de surveillance. La constitution d’une tumorotheque et d’une serotheque, s’inscrivant dans la demande de l’institut du cancer, est mise en place afin d’identifier des marqueurs diagnostiques, pronostiques et predictifs de la reponse therapeutique aux anti-angiogeniques actuellement en cours d’evaluation. L’objectif final est d’obtenir des donnees epidemiologiques, cliniques et histologiques permettant de recenser les cas sur le plan national, de realiser un suivi de l’histoire naturelle, d’evaluer l’efficacite des traitements medicaux (anti-angiogeniques, inhibiteurs de mTOR [mammalian target of rapamycin]...) et chirurgicaux innovants et d’etre le support de publications de series homogenes sur le plan international.

Results from randomized trials allow concluding that cisplatin-based chemotherapy is the standard first-line treatment for patients with advanced transitional cell carcinoma of the urothelium. However, there is no standard chemotherapy regimen emerging from the literature for elderly patients as prospective studies dedicated to this population are quite rare. In daily practice, because of a better safety profile, the combination of gemcitabine and cisplatin (with G-CSF support) probably is the best choice to recommend in patients who are considered as fit for cisplatin. In patients with impaired renal function and good performance status, the combination of gemcitabine and carboplatin would be the most acceptable option. When performance status is poor, gemcitabine alone is an option along with best supportive care.

Le cancer du rein (CR) represente dans les pays occidentaux environ 3 % des cancers de l’adulte. Dans le monde, le nombre de nouveaux CR est estime a 189 000 par an. Son incidence est estimee aux Etats-Unis par l’American Cancer Society a 51 590 nouveaux cas en 2007 avec un sex-ratio en faveur des hommes (31 990 hommes pour 19 600 femmes). Le nombre de deces par cancer renal y est evalue a 12 890 par an [1]. En France, il represente le 8e cancer pour l’incidence et le 12e pour la mortalite. En 2005, 8 000 nouveaux cancers du rein ont ete diagnostiques, et pres de 4 000 deces etaient directement lies [2]. La part de cette localisation dans l’ensemble des cancers a legerement augmente entre 1980 et 2005 dans toutes les regions chez les hommes passant, en moyenne, de 2,6 % a 3,1 % des cas. Cette part est stable chez les femmes, passant de 1,6 % a 1,9 % au cours de cette periode. Le sex-ratio est de 2 hommes pour 1 femme, et l’âge median au diagnostic est de 67 ans chez l’homme et de 70 ans chez la femme. Le pic d’incidence est observe vers 70 ans. La forme la plus frequente est sporadique, mais quelques formes hereditaires ont ete identifiees a ce jour. Tous stades confondus, la survie est de 50 % a 10 ans. Mais un tiers des patients presentent des metastases d’emblee au diagnostic avec une mediane de survie plus sombre.

La constatation historique du caractere hypervascularise des cancers du rein a cellules claires suggerait ľexistence ďune importante proliferation vasculaire. Ľacquisition ulterieure des connaissances concernant les mecanismes moleculaires impliques dans la carcinogenese renale a confirme le role particulierement important de ľangiogenese dans le developpement tumoral renal. La preuve du concept a ete recemment apportee par la demonstration ďun benefice clinique en situation metastatique lors de ľutilisation de molecules ciblant les effecteurs de ľangiogenese. Dans ce chapitre, nous rappellerons les bases physiopathologiques de ľangiogenese tumorale et les mecanismes ďaction des molecules antiangiogeniques, puis nous developperons les resultats des essais cliniques ayant permis de valider ľutilisation de ces molecules dans la pratique quotidienne.

Le cancer du rein, dont ľincidence augmente depuis 50 ans, represente 2 a 3% des tumeurs malignes de ľadulte; et 85000 nouveaux cas environ sont repertories chaque annee en Europe, dont 8300 en France (1). Ľhistologie la plus frequente est representee par le carcinome a cellules claires, retrouvee dans 70 a 80% des cas, suivie des carcinomes papillaire (10 a 20%) et chromophobe (5%) (2). Un tiers de ces patients est diagnostique au stade ďemblee metastatique, et 30% des patients presentant une forme localisee initiale developperont des metastases apres la nephrectomie (3, 4). Les armes therapeutiques disponibles pour ces formes metastatiques de cancer du rein a cellules claires sont limitees. En effet, ce dernier est repute etre hormono- et chimioresistant. Les taux de reponse obtenus avec la majorite des cytotoxiques sont inferieurs a 10% dans la plupart des etudes publiees (5, 6). Jusqu’a present, le traitement standard du cancer du rein a cellules claires metastatique (CRM) reposait sur ľimmunotherapie, basee sur ľutilisation de deux cytokines: ľinterleukine 2 (IL2) et ľinterferon α (IFN-α). Mais peu de patients vont beneficier de ce traitement, c’est-a-dire obtenir une reponse prolongee (7, 8). En 2007, elle semble devoir etre reservee aux patients de bon pronostic. Malgre une prise en charge medicochirurgicale des CRM metastatiques, la survie globale mediane reste limitee a 10–12 mois (9), et le taux de survie a 5 ans est inferieur a 10% (10).

Background Androgen deprivation therapy (ADT) is the standard treatment of hormone-sensitive metastatic prostate cancer (HSMPC). We performed a phase III multicentre trial to compare ADT alone with ADT plus docetaxel (D) in HNMPC. Methods Patients (pts) with HSMPC were randomly assigned to either arm A (ADT + D: 75mg/m q3w, up to 9 cycles) or arm B (ADT). The primary endpoint was overall survival (OS). The planned number of pts was 378 to detect an improvement in OS with a hazard ratio (HR) of 0.62, a power of 80% and an alpha risk of 0.05 (two-sided test). Secondary endpoints were biological progression-free survival (PFS) and clinical PFS. Data on toxicity and quality of life have been previously presented. Results From October 2004 to December 2008, 385pts were included. Baseline characteristics were well balanced between the two arms. Median age was 63 years (43-84), median PSA was 26.4 ng/ml (0.1-11900), Gleason score was ≥ 8 in 57%. Prognostic classification was as follows: good prognosis (49%), intermediate (29%) and poor (22%). The majority of pts had metastases at the time of diagnosis (72%), 28% developed metastases after local treatment failure. Median number of D cycles was 8 (range 0-9). The median follow-up was 50 months (mo) [95%CI: 49-54]. At 6 mo, a higher PSA response (≥ 50%) in arm A (94% vs 85%, p = 0.0096) and a higher PSA progression (≥ 25%) in arm B (10% vs 1%, p = 0.0015) were observed. Biological PFS was significantly longer in arm A: 22.9 vs 12.9 mo, HR; 0.72 [95%CI: 0.57-0.91] (p = 0.005). Clinical PFS was increase in arm A: 23.46 vs 15.44 mo, HR: 0.75 [95CI: 0.59-0.94] (0.015). OS was not significantly different (median: 58.9 mo in arm A and 54.2 mo in arm B, HR: 1.01 [95%CI: 0.75-1.36]. The median OS for each prognostic group was 69.1 [95%CI: 60.9-NR], 46.5 [95%CI: 37.7-NR] and 36.6 [95%CI9: 28.5-58.9] mo respectively in the good, intermediate, and poor prognosis groups (p = 0.001), with no difference between the two arms. At the cut-off time, 65% of pts from the ADT arm had received docetaxel since they developed castrate-resistant prostate cancer. Conclusion Combining docetaxel and ADT improves PFS over ADT alone in pts with HSMPC. However, no difference in OS was observed between the two arms. Disclosure G. Gravis: I have expert testimony to disclose: Sanofi Aventis, uncompensated. K. Fizazi: Participation to advisory boards and speaker for Sanofi-Aventis. F. Joly Lobbedez: advisory board/board of directors position: Sanofi, Roche, Pfizer, Novartis, Ferring; compensated consultant relationship: Roche, Novartis; honoraria: Sanofi, Roche, Pfizer, Novartis, Ferring, Ipsen,Takeda; travel remuneration: ASCO by Novartis, ESMO by Janssen. S. Oudard: I have an advisory relationship and honoraria to disclose: Pfizer Oncology, Bayer-Schering Pharma, Hoffman La Roche, Glaxo SmithKline, Novartis Pharma, Sanofi Aventis. D. Pouessel: Consultant role and honoraria: Sanofi, P. Beuzeboc: Presentations: Avantis, All other authors have declared no conflicts of interest.