BackgroundCOU-AA-301 trial has proved that abiraterone acetate (AA), a selective inhibitor of androgen biosynthesis, improved overall survival (OS) of patients with metastatic castration resistant prostate cancer (mCRPC) after a first line of docetaxel. Based on this result, a Temporary Authorization for Use (TAU) was performed between December 2010 and July 2011 to provide patients with mCRPC the opportunity to receive AA before its commercialization. The aim of this study was to evaluate safety and efficacy of AA treatment in this TAU.MethodsBetween December 2010 and July 2011, we conducted an ambispective, multicentric cohort study and investigated data from 20 centres participating to the AA TAU for patients presenting mCRPC and already treated by a first line of chemotherapy (CT). Statistical analyses of the data were performed using the Stata software v13 to identify predictive and prognostic factors.ResultsAmong the 408 patients, 306 were eligible with a follow-up at 3 years. Median OS was 37.1 months from beginning of CT and 14.6 months from AA introduction. 211 patients (69%) received ≥ 3 months of AA and 95 patients (31%) were treated less than 3 months. In the multivariate analyses, duration of AA was significantly correlated with PSA decrease at 3 months. Additionally, shorter time under AA treatment, presence of multiple sites of metastasis and previous hormonal treatment duration were three independent factors associated with poorer OS. At the time of analysis ten patients were still under treatment for more than 3 years.ConclusionsBiochemical response monitored by PSA changes at 3 months is a strong predictive factor for AA treatment duration. Some high responders’ patients could beneficiate from AA for more than 3 years.
PURPOSE Platinum-based doublets with concurrent and maintenance bevacizumab are standard therapy for ovarian cancer (OC) relapsing after a platinum-free interval (PFI) >6 months. Immunotherapy may be synergistic with bevacizumab and chemotherapy. PATIENTS AND METHODS ATALANTE/ENGOT-ov29 (ClinicalTrials.gov identifier: NCT02891824 ), a placebo-controlled double-blinded randomized phase III trial, enrolled patients with recurrent epithelial OC, one to two previous chemotherapy lines, and PFI >6 months. Eligible patients were randomly assigned 2:1 to atezolizumab (1,200 mg once every 3 weeks or equivalent) or placebo for up to 24 months, combined with bevacizumab and six cycles of chemotherapy doublet, stratified by PFI, PD-L1 status, and chemotherapy regimen. Coprimary end points were investigator-assessed progression-free survival (PFS) in the intention-to-treat (ITT) and PD-L1–positive populations (alpha .025 for each population). RESULTS Between September 2016 and October 2019, 614 patients were randomly assigned: 410 to atezolizumab and 204 to placebo. Only 38% had PD-L1–positive tumors. After 3 years' median follow-up, the PFS difference between atezolizumab and placebo did not reach statistical significance in the ITT (hazard ratio [HR], 0.83; 95% CI, 0.69 to 0.99; P = .041; median 13.5 v 11.3 months, respectively) or PD-L1–positive (HR, 0.86; 95% CI, 0.63 to 1.16; P = .30; median 15.2 v 13.1 months, respectively) populations. The immature overall survival (OS) HR was 0.81 (95% CI, 0.65 to 1.01; median 35.5 v 30.6 months with atezolizumab v placebo, respectively). Global health-related quality of life did not differ between treatment arms. Grade ≥3 adverse events (AEs) occurred in 88% of atezolizumab-treated and 87% of placebo-treated patients; grade ≥3 AEs typical of immunotherapy were more common with atezolizumab (13% v 8%, respectively). CONCLUSION ATALANTE/ENGOT-ov29 did not meet its coprimary PFS objectives in the ITT or PD-L1–positive populations. OS follow-up continues. Further research on biopsy samples is warranted to decipher the immunologic landscape of late-relapsing OC.
The treatment landscape in metastatic renal cell carcinoma has changed fundamentally over the last decade by the development of antiangiogenic agents, mammalian target of rapamycin inhibitors and immunotherapy. Outside of the context of a clinical trial, the treatments are used sequentially. We describe results under real‐life conditions of a sequential treatment strategy, before the era of immunotherapy. All patients were treated according to their prognostic score (either Memorial Sloan Kettering Cancer Center or International Metastatic Renal Cell Carcinoma Database Consortium) for advanced renal cell carcinoma. A treatment strategy involving 1 to 4 lines was determined including a rechallenge criterion for the repeat use of a treatment class. Three hundred forty‐four patients were included over 3 years. Overall survival was 57 months in patients with good or intermediate prognosis and 19 months in patients with poor prognosis. In the former group, the proportions of patients treated with 2 to 4 treatment lines were 70%, 38% and 16%, respectively. The best objective response rates for lines 1 to 4 were 46%, 36%, 16% and 17%, respectively. Grade III/IV toxicity did not appear to be cumulative. The recommended strategy was followed in 68% of patients. A large proportion of patients with good or intermediate prognosis who progress after two lines of treatment still have a performance status good enough to receive a systemic treatment, which justifies such a strategy. Overall survival of patients with good and intermediate prognosis was long, suggesting a benefit from the applied approach. These results might be used as selection criterion for the treatment of patients in the era of immune checkpoint inhibitors.
Sleep Apnea Syndrome (SAS) constitutes a healthcare issue of major importance at international level with a prevalence of 5% in the active population. Consequentially to the induced co-morbidities, the mortality reaches as high as 39% at eight years time lapse from the initial diagnostic. Seldom undiagnosed, the severity spectrum of SAS, in the absence of therapy, only continues to amplify. Here below, we are presenting the case of a 49 years old patient, railroad controller worker, non-smoker and occasionally alcohol user, who was hospitalized in our Clinic for Occupational Medicine. During last year, the patient was accusing excessive daytime somnolence, breath arrests during sleep, intense snoring, morning headaches, morning oral dryness, pin point chest pain, nocturia (4-5 nocturnal urination), concentration difficulties and an overall reduced work capacity. The presumptive diagnostic of Obstructive Sleep Apnea is being considered based on the correlation between the clinical presentation and the Epworth, Stanford and Berlin questionnaire results. The key diagnostic element was the polygraph recording over an 8 hours sleep period. Positive Diagnosis: Obstructive Sleep Apnea severe form. Management and recommendations: (1) Behavioral therapy (weight loss) and (2) CPAP (Continuous Positive Airway Pressure) therapy which was instituted immediately after the positive diagnosis was made. As a consequence, the respiratory symptoms, the frequent episodes of daytime snoozing and the concentration difficulties at work place diminished considerably.
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