Real-world dostarlimab use in advanced/recurrent endometrial cancer in France.

INTRODUCTION: In October 2020, the French Health Authority granted early access outside of the clinical trial setting for dostarlimab, a programmed death-1 inhibitor. Dostarlimab was approved by the European Medicines Agency (in April 2021) as monotherapy for patients with post-platinum mismatch repair deficient/microsatellite instability-high advanced/recurrent endometrial cancer, based on the results of the GARNET trial (NCT02715284). METHODS: This was a real-world descriptive analysis of patients granted cohort temporary authorization of use to receive dostarlimab between November 2020 and June 2021. Physicians could complete follow-up forms at each treatment cycle to provide clinical information, safety, and efficacy data. Safety and disease progression data were also captured through pharmacovigilance reports. RESULTS: Of 95 temporary authorization of use requests made by 80 oncologists in 59 French hospitals, 87 patients were eligible, and 80 received≥1 dose of dostarlimab. Based on treatment response assessments received (n=43), the mean (standard deviation) time from treatment initiation to response evaluation was 11 (6) weeks. The disease control rate (complete plus partial responses plus stable disease rates) was 56% (n=24/43), and the overall response rate was 35% (n=15/43); both consistent with those reported in the GARNET trial. No new safety signals were reported. DISCUSSION: The enrolment of 80 patients in an 8-month period highlights the need for access to novel treatment regimens in France for these patients post-platinum. Prospective randomized studies are ongoing to assess the efficacy and safety of dostarlimab and other checkpoint inhibitors as first-line treatment in patients with endometrial cancer.

Flexible dosing with paliperidone ER in the treatment of patients with acutely exacerbated schizophrenia: results from a single-arm, open-label study.

OBJECTIVE: To extend findings from fixed-dose, double-blind, placebo-controlled clinical trials in selected patient populations by using flexibly-dosed oral paliperidone extended-release (ER) in a more naturalistic setting. METHODS: Adults hospitalized with an acute exacerbation of schizophrenia were prospectively treated with open-label flexibly-dosed paliperidone ER 3-12 mg/day for 6 weeks. RESULTS: Overall, 294 patients were treated. The primary endpoint, defined as ≥30% improvement in Positive and Negative Syndrome Scale total scores from baseline to endpoint, was achieved by 66.3% of patients. The percentage of patients rated as at least 'markedly ill' in Clinical Global Impression of Severity scale decreased from baseline (74.1%) to endpoint (20.0%). Patient functioning, assessed by the Personal and Social Performance scale, improved significantly from 50.0 ± 14.3 at baseline to 63.6 ± 14.9 at endpoint (p < 0.0001). Concomitant benzodiazepines were newly initiated in 191 patients (65.0%), and new concomitant medications other than benzodiazepines were started after baseline for 133 patients (45.2%), most frequently paracetamol, zolpidem, and zopiclone. No unexpected adverse events were identified. CONCLUSIONS: These data support findings in more selected patient populations treated with fixed-dose paliperidone ER. Flexibly-dosed paliperidone ER administered in a naturalistic hospital setting to a more representative patient population experiencing an acute episode of schizophrenia, was associated with clinically meaningful treatment response. Strength of conclusions is limited by the open-label design and lack of a comparator group. Furthermore, some of the improvements observed may in part be associated with increased attention provided to patients and concomitant use of psychotropic medications, such as benzodiazepines, during this study.

Metabolic effects of paliperidone extended release versus oral olanzapine in patients with schizophrenia: a prospective, randomized, controlled trial.

Metabolic effects are generally more pronounced with second-generation than first-generation antipsychotics. This study was designed to compare long-term metabolic effects and efficacy of paliperidone extended release (ER) with those of oral olanzapine in patients with schizophrenia. In this 6-month, multicenter, prospective, randomized, controlled, open-label, parallel-group study, adults with schizophrenia were treated with paliperidone ER (6-9 mg/d; n = 239) or oral olanzapine (10-15 mg/d; n = 220). The primary outcome was mean change in the ratio of serum triglyceride level to high-density lipoprotein level (TG/HDL), a marker of insulin resistance. Other outcome measures included the Positive and Negative Syndrome Scale scores, measures of lipid and glucose metabolism, and body weight. Significant improvements in psychotic symptoms were observed with both treatments (P < 0.0001). The TG/HDL ratio was significantly higher at end point versus baseline with olanzapine compared with that of paliperidone ER. Mean end point change in TG/HDL ratio was 0.97 ± 2.72 [corrected] for olanzapine (P < 0.0001, reflecting worsening), with no significant change for paliperidone ER (-0.17 ± 2.51). Newly diagnosed impairment in TG and metabolic syndrome was more common with olanzapine (P < 0.05). Insulin resistance, as measured by the homeostasis model assessment of insulin resistance, worsened significantly with olanzapine (P = 0.0003), but not with paliperidone ER. Glucose sensitivity for insulin worsened significantly with olanzapine (P < 0.03), with no significant changes for paliperidone ER. End point increase in body weight was significantly higher with olanzapine than paliperidone ER (3.8 vs 1.2 kg; P = 0.0013). In summary, both paliperidone ER and olanzapine effectively treated schizophrenia; however, undesirable metabolic effects were significantly greater with olanzapine.

[Two thirds of patients with gastroesophageal reflux have nocturnal symptoms: survey by 562 general practitioners of 36,663 patients]. / Deux tiers des malades ayant un reflux gastro-oesophagien ont des symptômes nocturnes: enquête réalisée par 562 médecins auprès de 36,663 patients.

OBJECTIVE: Gastroesophageal reflux disease (GERD) affects about 10% of the French population, who have symptoms at least weekly. Nocturnal symptoms are associated with more severe disease. The aim of this study was to determine the prevalence of nocturnal reflux symptoms among patients seeing general practitioners and to assess their consequences on sleep quality. METHODS: For three consecutive days, 562 general practitioners identified among all the adult patients they saw those with GERD symptoms (heartburn or regurgitation) in the previous 3 months and characterized the symptoms. RESULTS: Prevalence of GERD among the 36663 consulting patients was 8.3%, and 64.6% of them (that is, 5.4% of the general population) reported nocturnal GERD. Patients with nocturnal symptoms did not differ from those with only diurnal symptoms except smokers had a significantly higher rate of nocturnal than diurnal symptoms (28 versus 23%, p=0.0053). GERD symptoms were related to nocturnal awakening in 58.6% of patients, were present in the early morning for 41.6% and in the evening at bedtime for 39.5%. Nocturnal awakening, difficulty in falling asleep and nightmares occurred significantly more frequently in patients with nocturnal symptoms (respectively 56 versus 24%; 41 versus 31%; 14 versus 9%). Likewise, atypical nondigestive symptoms occurred significantly more frequently in patients with nocturnal symptoms (74 versus 51%, p<0.0001). Quality of sleep was considered "poor or very poor" more frequently in patients with nocturnal symptoms (58 versus 34%, p<0.0001). CONCLUSION: Approximately 2/3 of GERD patients have nocturnal symptoms that appear to have a significant negative impact on sleep and well-being. These results show the need to evaluate specific therapeutic approaches to reduce sleep disturbances in these patients.

The INFVo perceptual rating scale for substitution voicing: development and reliability.

In this paper, an experimental study of inter-judge consistency for the different dimensions of a recently proposed new scale for the rating of substitution voices is presented. The IINFVo rating scale tries to score five parameters, namely impression, intelligibility, noise, fluency and voicing. Each parameter is scored between 0 (very good substitution voicing) and 10 (very deviant substitution voicing) on a visual analogue scale. Inter-judge consistencies were measured among semi-professional as well as among professional jury members. The consistencies among semi-professionals, expressed as Pearson correlation coefficients, ranged from moderate to good (0.57-0.68), whereas those among professionals were good to excellent (0.82-0.87) and compared favourably to consistency figures published for traditional perceptual evaluation scales such as the GRBAS scale for laryngeal dysphonia. Since there is a strong correlation between the scores of impression and intelligibility, and since intelligibility is hard to score by non-native listeners, we suggest taking the mean of the two scores as the "impression" of a modified dimensional INFVo rating scale. Our experiments demonstrate that the INFVo rating scale has good potential to become a routine perceptual evaluation method in a multidimensional assessment protocol for substitution voicing.