Impact de la séquence thérapeutique entre les taxanes et les inhibiteurs de l’axe du récepteur des androgènes dans la prise en charge du cancer de prostate résistant à la castration

Background: the optimal sequence of life-extending therapies in metastatic castration-resistant prostatecancer (mCRPC) is unknown.Objective: to evaluate outcomes of mCRPC patients treated with DOC (DOC), CABA (CABA) and a novelandrogen receptor-targeted agent (iARA) (abiraterone acetate or ENZA), according to 3 different sequences.Patients and methods Data from 669 consecutive mCRPC patients were retrospectively collected betweenNovember 2012 and October 2016. Primary endpoint was prostate-specific antigen (PSA) response (decrease≥50% from baseline) with each therapy. Secondary endpoints included best clinical benefit, time to PSAprogression, radiological progression-free survival (rPFS), overall survival (OS) and toxicity.Results: 158 patients received DOC®CABA®iARA (Group 1), 456 received DOC®iARA®CABA (Group 2),and 55 received iARA®DOC®CABA (Group 3). At baseline, PSA progression only and Gleason <8 weremore common in Group 3. PSA response on DOC was lower in Group 3 than in other groups (p=0.02) andPSA response on CABA was higher in second than in third line (p=0.001). In Group 3, rPFS on iARA (6.6months) and DOC (9.2 months) were also shorter than in other groups. OS calculated from the first lifeextendingtherapy reached 34.8, 35.8 and 28.9 months in Groups 1, 2 and 3, respectively (p=0.007). Toxicitywas comparable between arms.Conclusions: in this retrospective trial, sequencing of DOC, CABA and one iARA, was associated with amedian OS of up to 35.8 months. CABA seemed to retain its activity regardless treatment sequence. DOCactivity after iARA appeared to be reduced, but data were insufficient to conclude cross-resistance.Contexte : la séquence optimale des traitements dans le cancer de la prostate métastatique résistant à lacastration (CPRCm) est inconnue.Objectif : évaluer le devenir des patients atteints de CPRCm traités par Docetaxel (DOC), Cabazitaxel (CABA)et un nouvel agent ciblant les récepteurs des androgènes (iARA) (acétate d'Abiratérone ou Enzalutamide),selon 3 séquences différentes.Patients et méthodes : les données de 669 patients consécutifs atteints de CPRCm ont été recueilliesrétrospectivement entre novembre 2012 et octobre 2016. Le critère d'évaluation principal était la réponsebiologique du PSA (diminution ≥ 50% par rapport à la valeur initiale) pour chaque traitement. Les critèressecondaires étaient le meilleur bénéfice clinique, le délai jusqu’à progression du PSA, la survie globale (SG) etla toxicité.Résultats : 158 patients ont reçu DOC®CABA®iARA (groupe 1), 456 ont reçu DOC®iARA®CABA (groupe 2)et 55 ont reçu iARA®DOC®CABA (groupe 3). Au départ, la progression biologique seule et un score deGleason <8 étaient plus fréquents dans le groupe 3. La réponse du PSA sous DOC était plus faible dans legroupe 3 que dans les autres groupes (p = 0,02) et la réponse du PSA sur CABA était plus élevée endeuxième qu'en troisième ligne (p = 0,001). La SG calculée à partir du premier traitement a atteint 34,8, 35,8 et28,9 mois dans les groupes 1, 2 et 3 (p = 0,007). La toxicité était comparable entre les bras.Conclusions : la séquence du DOC, du CABA et d'une iARA permettrait d’atteindre une SG médiane allantjusqu'à 35,8 mois. Le CABA semble conserver son activité indépendamment de la séquence. L' activité duDOC après l’iARA semble être réduite

Identifying homogeneous healthcare use profiles and treatment sequences by combining sequence pattern mining with care trajectory clustering in kidney cancer patients on oral anticancer drugs: A case study

International audienceObjective We evaluated the ability of a coupled pattern-mining and clustering method to identify homogeneous groups of subjects in terms of healthcare resource use, prognosis and treatment sequences, in renal cancer patients beginning oral anticancer treatment. Methods Data were retrieved from the permanent sample of the French medico-administrative database. We applied the CP-SPAM algorithm for pattern mining to healthcare use sequences, followed by hierarchical clustering on principal components (HCPC). Results and conclusion We identified 127 individuals with renal cancer with a first reimbursement of an oral anticancer drug between 2010 and 2017. Clustering identified three groups of subjects, and discrimination between these groups was good. These clusters differed significantly in terms of mortality at six and 12 months, and medical follow-up profile (predominantly outpatient or inpatient care, biological monitoring, reimbursement of supportive care drugs). This case study highlights the potential utility of applying sequence-mining algorithms to a large range of healthcare reimbursement data, to identify groups of subjects homogeneous in terms of their care pathways and medical behaviors

The impact of the Paris terrorist attacks on the mental health of resident physicians

Abstract Background On November 13, 2015, terrorist attacks took place in Paris. One hundred and twenty-nine people were immediately killed and 302 needed emergency care. Many resident physicians were on the front line of the medical response. Our aim was to report the frequency of symptoms of post-traumatic stress disorder (PTSD), anxiety and depression among resident physicians after the Paris terrorist attacks. Methods Anonymous questionnaires, including the Impact of Event Scale- Revised (IES-R) and the Hospital Anxiety and Depression Scale (HADS), were emailed two months after the attacks to 2413 Parisian resident physicians. Exposure to the attacks was defined as having direct clinical contact with one of the victims up to one week after the attacks, being one of the victims, or having one among close relatives. Results The questionnaire was completed by 680 (28.2%) residents. Eighty-four (12.4%) reported symptoms of PTSD (IES-R ≥ 33), 76 (11.2%) reported symptoms of anxiety (HADS anxiety score > 10) and 16 (2.4%) reported symptoms of depression (HADS depression score > 10). Exposed residents had higher IES-R scores than non-exposed residents (18.8 ± 16.6 versus 14.2 ± 12.0, p = 0.001), and 40 (18.5%) of them reported symptoms of PTSD, compared to 44 (9.5%) of the non-exposed residents (p = 0.001). Conclusions There was a high frequency of symptoms of mental distress among our respondents. Dedicated screening and care strategies must be considered in the event of new attacks

Pharmaceutical consultation to detect drug interactions in patients treated with oral chemotherapies: A descriptive cross‐sectional study

International audienc

Clinical Impact of Lymphadenectomy after Neoadjuvant Chemotherapy in Advanced Epithelial Ovarian Cancer: A Review of Available Data

Recent robust data allow for omitting lymph node dissection for patients with advanced epithelial ovarian cancer (EOC) and without any suspicion of lymph node metastases, without compromising recurrence-free survival (RFS), nor overall survival (OS), in the setting of primary surgical treatment. Evidence supporting the same postulate for patients undergoing complete cytoreductive surgery after neoadjuvant chemotherapy (NACT) is lacking. Throughout a systematic literature review, the aim of our study was to evaluate the impact of lymph node dissection in patients undergoing surgery for advanced-stage EOC after NACT. A total of 1094 patients, included in six retrospective series, underwent either systematic, selective or no lymph node dissection. Only one study reveals a positive effect of lymphadenectomy on OS, and two on RFS. The four remaining series fail to demonstrate any beneficial effect on survival, neither for RFS nor OS. All of them highlight the higher peri- and post-operative complication rate associated with systematic lymph node dissection. Despite heterogeneity in the design of the studies included, there seems to be a trend showing no improvement on OS for systematic lymph node dissection in node negative patients. A well-conducted prospective trial is mandatory to evaluate this matter

Impact of progression at baseline and on-treatment progression events in three large prostate cancer trials.

There is a discussion about the optimal timing to initiate or switch treatment in metastatic castration-resistant prostate cancer (mCRPC). This post hoc analysis of 3 large trials for men with mCRPC examined the influence of the type of progression at initiation of first-line chemotherapy, as well as the type of progression during treatment, on treatment outcomes. Data from the phase III studies VENICE (n = 1224), TAX327 (n = 1006) and FIRSTANA (n = 1168) were used as independent data sets. Type of progression was defined as follows: prostate-specific antigen (PSA) only (group 1), radiological (±PSA) (group 2) or pain (±PSA, ± radiological) progression (group 3). The impact of baseline type of progression on overall survival (OS) was evaluated in multivariate Cox regression analysis with backward elimination, stratified for the Eastern Cooperative Oncology Group performance score and treatment arm. The median OS (arms combined) from treatment initiation in VENICE was 28.6, 26.3 and 16.9 months for G1, G2 and G3, respectively (hazard ratio: 1.14 [95% confidence interval {CI}: 0.92-1.41%] in G2 and 2.13 [95% CI: 1.75-2.59%] in G3 compared with G1). Multivariate analysis (arms combined) showed that pain progression at baseline was an independent predictor of poor OS. Similar findings were observed in the TAX327 and FIRSTANA data sets. During treatment, pain or radiological progression preceded PSA progression in ~55% of the patients. The retrospective characteristic of this study is a limitation. The type of progression at baseline strongly predicts OS in men with mCRPC treated with first-line chemotherapy. During treatment, pain and/or radiological progression preceded PSA progression as the first progression event in ~55% of the patients. This finding has the prospect to be incorporated in clinical guidelines and to be practice changing because it implies the need for regular imaging and not to rely on PSA progression alone

Prostate-specific antigen flare induced by cabazitaxel-based chemotherapy in patients with metastatic castration-resistant prostate cancer

Background: A prostate-specific antigen (PSA) flare occurs in about 15% of metastatic castration-resistant prostate cancer (mCRPC) patients receiving docetaxel. This flare has no standard definition. Its impact on treatment efficacy is unclear. We sought to evaluate the incidence and characteristics of PSA flare on cabazitaxel, and its impact on survival