Efficacy and safety of duloxetine 60 mg once daily in the treatment of pain in patients with major depressive disorder and at least moderate pain of unknown etiology: a randomized controlled trial

OBJECTIVE: Experience of pain in major depressive disorder (MDD) can complicate diagnosis and impair treatment outcomes. This study evaluated the efficacy and safety of duloxetine in the treatment of patients with moderate pain associated with depression. METHOD: In this double-blind, placebo-controlled, 8-week study, conducted from May 2005 to May 2006, outpatients 18 years of age or older, presenting with major depressive disorder (DSM-IV criteria; Montgomery-Asberg Depression Rating Scale [MADRS] score >or= 20), moderate pain (Brief Pain Inventory-Short Form [BPI-SF] average pain score >or= 3), and Clinical Global Impressions-Severity of Illness scale (CGI-S) score >or= 4 were randomly assigned to either placebo (N = 165) or duloxetine 60 mg (N = 162) once daily. Primary outcome was change in item 5 score (average pain in the last 24 hours) of the BPI-SF from baseline. Secondary measures were MADRS total score, other BPI-SF items, CGI-S, CGI-Improvement scale, Patient Global Impressions-Improvement scale, Symptom Checklist-90-Revised, response and remission rates, safety, and tolerability. RESULTS: Duloxetine, compared with placebo, significantly reduced pain and improved depression with significant mean changes at endpoint in both BPI-SF average pain scores (-2.57 vs. -1.64, p or= 10%) in duloxetine-treated patients were nausea, hyperhidrosis, and dry mouth. CONCLUSION: These results support duloxetine's efficacy and tolerability in the treatment of pain and depression in patients with at least moderate pain associated with depression. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT00191919 (http://www.clinicaltrials.gov).status: publishe

Minimal clinically important difference in parkinson's disease as assessed in pivotal trials of pramipexole extended release

Background. The minimal clinically important difference (MCID) is the smallest change in an outcome measure that is meaningful for patients. Objectives. To calculate the MCID for Unified Parkinson’s Disease Rating Scale (UPDRS) scores in early Parkinson’s disease (EPD) and for UPDRS scores and “OFF” time in advanced Parkinson’s disease (APD). Methods. We analyzed data from two pivotal, double-blind, parallel-group trials of pramipexole ER that included pramipexole immediate release (IR) as an active comparator. We calculated MCID as the mean change in subjects who received active treatment and rated themselves “a little better” on patient global impression of improvement (PGI-I) minus the mean change in subjects who received placebo and rated themselves unchanged. Results. MCIDs in EPD (pramipexole ER, pramipexole IR) for UPDRS II were −1.8 and −2.0, for UPDRS III −6.2 and −6.1, and for UPDRS II + III −8.0 and −8.1. MCIDs in APD for UPDRS II were −1.8 and −2.3, for UPDRS III −5.2 and −6.5, and for UPDRS II + III −7.1 and −8.8. MCID for “OFF” time (pramipexole ER, pramipexole IR) was −1.0 and −1.3 hours. Conclusions. A range of MCIDs is emerging in the PD literature that provides the basis for power calculations and interpretation of clinical trials

First-line afatinib plus cetuximab for EGFR-mutant non–small cell lung cancer: Results from the randomized phase II IFCT-1503 ACE-lung study

International audiencePurpose: Double inhibition of epidermal growth factor receptor (EGFR) using a tyrosine kinase inhibitor plus a monoclonal antibody may be a novel treatment strategy for non–small cell lung cancer (NSCLC). We assessed the efficacy and toxicity of afatinib þ cetuximab versus afatinib alone in the first-line treatment of advanced EGFR-mutant NSCLC. Patients and Methods: In this phase II, randomized, open-label study, patients with stage III/IV EGFR-positive NSCLC were randomly assigned (1:1) to receive afatinib (group A) or afatinib þ cetuximab (group A þ C). Oral afatinib 40 mg was given once daily; cetuximab 250 mg/m2 was administered intravenously on day 15 of cycle 1, then every 2 weeks at 500 mg/m2 for 6 months. The primary endpoint was time to treatment failure (TTF) rate at 9 months. Exploratory analysis of EGFR circulating tumor DNA in plasma was performed. Results: Between June 2016 and November 2018, 59 patients were included in group A and 58 in group A þ C. The study was ended early after a futility analysis was performed. The percentage of patients without treatment failure at 9 months was similar for both groups (59.3% for group A vs. 64.9% for group A þ C), and median TTF was 11.1 (95% CI, 8.5–14.1) and 12.9 (9.2–14.5) months, respectively. Other endpoints, including progression-free survival and overall survival, also showed no improvement with the combination versus afatinib alone. There was a slight numerical increase in grade ≥3 adverse events in group A þ C. Allele frequency of the EGFR gene mutation in circulating tumor DNA at baseline was associated with shorter PFS, regardless of the treatment received. Conclusions: These results suggest that addition of cetuximab to afatinib does not warrant further investigation in treatment-naïve advanced EGFR-mutant NSCLC

Nivolumab or nivolumab plus ipilimumab in patients with relapsed malignant pleural mesothelioma (IFCT-1501 MAPS2): a multicentre, open-label, randomised, non-comparative, phase 2 trial

International audienceThere is no recommended therapy for malignant pleural mesothelioma that has progressed after first-line pemetrexed and platinum-based chemotherapy. Disease control has been less than 30% in all previous studies of second-line drugs. Preliminary results have suggested that anti-programmed cell death 1 (PD-1) monoclonal antibody could be efficacious in these patients. We thus aimed to prospectively assess the anti-PD-1 monoclonal antibody alone or in combination with anti-cytotoxic T-lymphocyte protein 4 (CTLA-4) antibody in patients with malignant pleural mesothelioma

Two-year survival with nivolumab in previously treated advanced non–small-cell lung cancer: a real-world pooled analysis of patients from France, Germany, and Canada

Objectives: Immune checkpoint inhibitors have become the standard of care for metastatic non–small-cell lung cancer (NSCLC) progressing during or after platinum-based chemotherapy. Real-world clinical practice tends to represent more diverse patient characteristics than randomized clinical trials. We sought to evaluate overall survival (OS) outcomes in the total study population and in key subsets of patients who received nivolumab for previously treated advanced NSCLC in real-world settings in France, Germany, or Canada. Materials and methods: Data were pooled from two prospective observational cohort studies, EVIDENS and ENLARGE, and a retrospective registry in Canada. Patients included in this analysis were aged ≥18 years, had stage IIIB/IV NSCLC, and received nivolumab after at least one prior line of systemic therapy. OS was estimated in the pooled population and in various subgroups using the Kaplan-Meier method. Timing of data collection varied across cohorts (2015–2019). Results: Of the 2585 patients included in this analyses, 1235 (47.8 %) were treated in France, 881 (34.1 %) in Germany, and 469 (18.1 %) in Canada. Median OS for the total study population was 11.3 months (95 % CI: 10.5–12.2); this was similar across France, Germany, and Canada. The OS rate was 49 % at 1 year and 28 % at 2 years for the total study population. In univariable Cox analyses, the presence of epidermal growth factor receptor mutations in nonsquamous disease, liver, or bone metastases were associated with significantly shorter OS, whereas tumor programmed death ligand 1 expression and Eastern Cooperative Oncology Group performance status 0–1 were associated with significantly prolonged OS. Similar OS was noted across subgroups of age and prior lines of therapy. Conclusion: OS rates in patients receiving nivolumab for previously treated advanced NSCLC in real-world clinical practice closely mirrored those in phase 3 studies, suggesting similar effectiveness of nivolumab in clinical trials and clinical practice

The burden of mild asthma: Clinical burden and healthcare resource utilisation in the NOVELTY study

Background: Patients with mild asthma represent a substantial proportion of the population with asthma, yet there are limited data on their true burden of disease. We aimed to describe the clinical and healthcare resource utilisation (HCRU) burden of physician-assessed mild asthma.Methods: Patients with mild asthma were included from the NOVEL observational longiTudinal studY (NOVELTY; NCT02760329), a global, 3-year, real-world prospective study of patients with asthma and/or chronic obstructive pulmonary disease from community practice (specialised and primary care). Diagnosis and severity were based on physician discretion. Clinical burden included physician-reported exacerbations and patient-reported measures. HCRU included inpatient and outpatient visits.Results: Overall, 2004 patients with mild asthma were included; 22.8% experienced ≥1 exacerbation in the previous 12 months, of whom 72.3% experienced ≥1 severe exacerbation. Of 625 exacerbations reported, 48.0% lasted >1 week, 27.7% were preceded by symptomatic worsening lasting >3 days, and 50.1% required oral corticosteroid treatment. Health status was moderately impacted (St George's Respiratory Questionnaire score: 23.5 [standard deviation ± 17.9]). At baseline, 29.7% of patients had asthma symptoms that were not well controlled or very poorly controlled (Asthma Control Test score <20), increasing to 55.6% for those with ≥2 exacerbations in the previous year. In terms of HCRU, at least one unscheduled ambulatory visit for exacerbations was required by 9.5% of patients, including 9.2% requiring ≥1 emergency department visit and 1.1% requiring ≥1 hospital admission.Conclusions: In this global sample representing community practice, a significant proportion of patients with physician-assessed mild asthma had considerable clinical burden and HCRU

Treatable traits in the NOVELTY study

CorrigendumVolume 27, Issue 12, Respirology, pages: 1095-1095. First Published online: November 6, 2022 10.1111/resp.14406International audienceAsthma and chronic obstructive pulmonary disease (COPD) are two prevalent and complex diseases that require personalized management. Although a strategy based on treatable traits (TTs) has been proposed, the prevalence and relationship of TTs to the diagnostic label and disease severity established by the attending physician in a real-world setting are unknown. We assessed how the presence/absence of specific TTs relate to the diagnosis and severity of 'asthma', 'COPD' or 'asthma + COPD'