Comorbidities of COPD Cavaillès, Arnaud; Brinchault-Rabin, Graziella; Dixmier, Adrien ...
European respiratory review
22, Issue:
130
Journal Article
Peer reviewed
Open access
By 2020, chronic obstructive pulmonary disease (COPD) will be the third cause of mortality. Extrapulmonary comorbidities influence the prognosis of patients with COPD. Tobacco smoking is a common ...risk factor for many comorbidities, including coronary heart disease, heart failure and lung cancer. Comorbidities such as pulmonary artery disease and malnutrition are directly caused by COPD, whereas others, such as systemic venous thromboembolism, anxiety, depression, osteoporosis, obesity, metabolic syndrome, diabetes, sleep disturbance and anaemia, have no evident physiopathological relationship with COPD. The common ground between most of these extrapulmonary manifestations is chronic systemic inflammation. All of these diseases potentiate the morbidity of COPD, leading to increased hospitalisations and healthcare costs. They can frequently cause death, independently of respiratory failure. Comorbidities make the management of COPD difficult and need to be evaluated and treated adequately.
Women and COPD: do we need more evidence? Gut-Gobert, Christophe; Cavaillès, Arnaud; Dixmier, Adrien ...
European respiratory review,
03/2019, Volume:
28, Issue:
151
Journal Article
Peer reviewed
Open access
The increasingly female face of chronic obstructive pulmonary disease (COPD) prevalence among women has equalled that of men since 2008, due in part to increased tobacco use among women worldwide and ...exposure to biomass fuels. This finding is supported by a number of characteristics. There is evidence of susceptibility to smoking and other airborne contaminants, along with epidemiological and phenotypic manifestations. COPD has thus become the leading cause of death in women in the USA. The clinical presentation is characterised by increasingly pronounced dyspnoea with a marked tendency towards anxiety and depression, undernutrition, nonsmall cell lung cancer (especially adenocarcinoma) and osteoporosis. Quality of life is also more significantly impacted. The theories advanced to explain these differences involve the role played by oestrogens, impaired gas exchange in the lungs and smoking habits. While these differences require appropriate therapeutic responses (smoking cessation, pulmonary rehabilitation, long-term oxygen therapy), barriers to the treatment of women with COPD include greater under-diagnosis than in men, fewer spirometry tests and medical consultations. Faced with this serious public health problem, we need to update and adapt our knowledge to the epidemiological changes.
EVIDENS is an ongoing, prospective, non-interventional study evaluating the effectiveness and safety of nivolumab in lung cancer patients in France (ClinicalTrials.gov NCT03382496).
Adults with a ...pathologically confirmed diagnosis of lung cancer and initiating treatment with nivolumab were recruited from 146 sites in France. This analysis included only patients with non-small cell lung cancer (NSCLC) who received ≥1 nivolumab infusion, and evaluated patient characteristics at the time of nivolumab initiation and its effectiveness and safety after a median follow-up of 18 months.
A total of 1,420 patients with NSCLC were included, most of whom had an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0-1 (82.9%), non-squamous histology (69.2%) and stage IV disease (91.4%). Brain metastases were present in 19.9% of patients. Nivolumab was a second-line or ≥third-line regimen in 73.6% and 26.1% of patients, respectively. Almost all patients had prior chemotherapy (99.7%). Median overall survival was 11.2 months (95% confidence interval CI: 10.0-12.4). ECOG PS, smoking status, corticosteroids at baseline, epidermal growth factor receptor mutation status, presence of symptomatic brain metastases and treatment-related adverse events (TRAEs) were independent predictors of survival. Grade 3 and 4 TRAEs were reported in 105 (7.4%) and 12 (0.8%) patients, respectively; no treatment-related deaths were reported.
Preliminary results of the EVIDENS study confirm the effectiveness and safety of nivolumab, mostly in pre-treated advanced NSCLC patients, with similar benefits to those observed in the phase III randomized clinical trials, despite a broader study population.
Second-line chemotherapy regimens have demonstrated poor benefit after failure of platinum-based chemotherapy in advanced non-squamous non–small-cell lung cancer (nsNSCLC).
In this multicentre, ...open-label phase III trial, patients with advanced nsNSCLC treated with one or two prior lines, including one platinum-based doublet, were centrally randomised to receive 90 mg/m2 of paclitaxel (D1, D8, D15) plus 10 mg/kg of bevacizumab (D1, D15) every 28 days or docetaxel (75 mg/m2) every 21 days; crossover was allowed after disease progression. Primary end-point was progression-free survival (PFS). ClinicalTrials.gov registration number: NCT01763671.
One hundred sixty six patients were randomised (paclitaxel plus bevacizumab: 111, docetaxel: 55). The median PFS was longer in patients receiving paclitaxel plus bevacizumab than in patients receveing docetaxel 5·4 months versus 3·9 months, adjusted hazard ratio (HR) 0·61 (95% confidence interval CI: 0·44–0·86); p = 0·005. Objective response rates (ORRs) were 22·5% (95% CI: 14·8–30·3) and 5·5% (95% CI: 0·0–11·5) (p = 0·006), respectively. Median overall survivals were similar (adjusted HR 1·17; p = 0·50). Crossover occurred in 21 of 55 (38·2%) docetaxel-treated patients. Grade III-IV adverse events (AEs) were reported in 45·9% and 54·5% of patients treated with paclitaxel and bevacizumab or docetaxel, respectively (p = NS), including neutropenia (19·3% versus 45·4%), neuropathy (8·3% versus 0·0%) and hypertension (7·3% versus 0·0%). Three patients died due to treatment-related AEs (1·8% in each group).
Weekly paclitaxel plus bevacizumab as second- or third-line improves PFS and ORR compared with docetaxel in patients with nsNSCLC, with an acceptable safety profile. These results place weekly paclitaxel plus bevacizumab as a valid option in this population.
ClinicalTrials.gov Identifier: NCT01763671.
•Prognosis of patients with advanced non–small-cell lung cancer (NSCLC) is poor.•Few options beyond platinum-based chemo and immunotherapy in non-squamous (ns) NSCLC.•Phase III trial of bevacizumab-paclitaxel (wPB) or docetaxel in 2nd/3rd line nsNSCLC.•wPB improved progression-free survival and objective response rate.•Safety profile was manageable and Quality of Life was preserved with wPB.
•French real world study reviewed first-line extensive-stage SCLC patient data from national real world data cohort.•Participating non-academic hospitals mainly used standard-of-care platinum and ...etoposide chemotherapy.•Patients receiving cisplatin + etoposide were younger and fitter than those receiving carboplatin + etoposide.•Median OS of chemotherapy-treated first-line extensive-stage SCLC patients varied from 7 to 10 months.•Patients treated with cisplatin + etoposide showed better OS and 1 year survival rates.
FRESC reanalyzed extensive-stage small-cell lung cancer (ES-SCLC) patient data from the French KBP-2010 cohort to describe the characteristics and therapeutic management of ES-SCLC and provide real-world estimates of survival.
A target population of first line (1L) ES-SCLC was identified at initial diagnosis in KBP-2010 (KBP population, N = 796). A KBP-2010 subpopulation was defined as patients who also met the IMpower133 clinicaltrial PS ≤ 1 inclusion criteria (KBP-PS_0/1 population, N = 394). Subgroups were defined according to the 1L ES-SCLC chemotherapy regimens: carboplatin or cisplatin with etoposide (Carb-E or Cisp-E subgroups).
The vast majority of KBP populations exhibited stage IV ES-SCLC (84.9%) at initial diagnosis. Median age was 66 years; patients were mostly male and smokers. Patients receiving Cisp + Eto were younger (median age 61 years 55.0–67.0) and fitter (25.5% had PS ≥ 2) than those receiving Carb + Eto (71 years 62.5–77.5; 44.1%had PS ≥ 2). Median overall survival (OS) of chemotherapy-treated 1L ES-SCLC patients varied from 7.0 months 95% CI, 6.1; 7.8 in the KBPCarb-Esubgroups to 9.6 months 95% CI, 8.4;10.8 in the KBP Cisp-E subgroup. KBP-PS_0/1 population showed better median OS, especially for the Cisp-E subgroup (10 months 95% CI, 8.7; 11.3).
In the KBP-PS_0/1 population, median OS was close to the one that was found in the IMpower133 control arm. Although this needs to be confirmed by further research, it suggests the transposability of the IMpower133 results to real-life conditions.
Une patiente présenta une méningite carcinomateuse d’étiologie indéterminée. L’identification d’une mutation EGFR des cellules tumorales permis le diagnostic et le traitement du cancer.
Une patiente ...non fumeuse de 60 ans, sans antécédent personnel ou familial de néoplasie a été prise en charge en neurologie à l’hôpital d’Orléans en mai 2016 pour un tableau de céphalées et cervicalgies d’aggravation progressive pendant 1 an avec hypertension intracrânienne. La ponction lombaire a mis en évidence une méningite carcinomateuse. Les cellules anormales du LCR étaient TTF1+ ce qui était en faveur d’une origine pulmonaire. Aucune néoplasie primitive, en particulier pulmonaire, n’a pu être identifiée malgré un bilan complet. Une mutation EGFR L858R a été retrouvée dans les cellules du LCR et le diagnostic de néoplasie pulmonaire a pu être posé. Un traitement par géfitinib a été débuté avec une évolution clinique favorable.
Le pronostic des méningites carcinomateuses est mauvais. L’analyse d’ADN des cellules carcinomateuses est intéressante chez les patients sans néoplasie primitive retrouvée, malgré un bilan extensif. La présence d’une mutation EGFR chez cette patiente a permis le diagnostic d’adénocarcinome pulmonaire malgré l’absence de lésion pulmonaire, et un traitement par chimiothérapie spécifique, avec un impact pronostic important.
Notre cas illustre la nécessité de recherche des mutations EGFR dans le LCR chez les patients ayant une méningite carcinomateuse sans néoplasie primitive pulmonaire retrouvée.
•Median overall survival (OS) was 11.3 months and similar across the 3 countries.•OS rates were 49 % at 1 year and 28 % at 2 years for the total study population.•OS rates were ≈20 % at 2 years in ...ECOG PS ≥ 2, liver, and bone metastasis subgroups.•Median OS and OS rates were independent of age and prior lines of therapy.•Nivolumab effectiveness in real-world settings was consistent with phase 3 trials.
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.
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).
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.
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.
Lung cancer in never-smokers (LCINS) (fewer than 100 cigarettes in lifetime) is considered as a distinct entity and harbours an original molecular profile. However, the epidemiological and molecular ...features of LCINS in Europe remain poorly understood. All consecutive newly diagnosed LCINS patients were included in this prospective observational study by 75 participating centres during a 14-month period. Each patient completed a detailed questionnaire about risk factor exposure. Biomarker and pathological analyses were also collected. We report the main descriptive overall results with a focus on sex differences. 384 patients were included: 65 men and 319 women. 66% had been exposed to passive smoking (significantly higher among women). Definite exposure to main occupational carcinogens was significantly higher in men (35% versus 8% in women). A targetable molecular alteration was found in 73% of patients (without any significant sex difference): EGFR in 51%, ALK in 8%, KRAS in 6%, HER2 in 3%, BRAF in 3%, PI3KCA in less than 1%, and multiple in 2%. We present the largest and most comprehensive LCINS analysis in a European population. Physicians should track occupational exposure in men (35%), and a somatic molecular alteration in both sexes (73%).
Occupational exposure constitutes a common risk factor for lung cancer. We observed molecular alterations in 73% of never-smokers, 35% of men and 8% of women were exposed to at least one occupational ...carcinogen. We report herein associations between molecular patterns and occupational exposure.BioCAST was a cohort study of lung cancer in never-smokers that reported risk factor exposure and molecular patterns. Occupational exposure was assessed
a validated 71-item questionnaire. Patients were categorised into groups that were unexposed and exposed to polycyclic aromatic hydrocarbons (PAH), asbestos, silica, diesel exhaust fumes (DEF), chrome and paints. Test results were recorded for
and
mutations, and
alterations.Overall, 313 out of 384 patients included in BioCAST were analysed. Asbestos-exposed patients displayed a significantly lower rate of
mutations (20%
44%, p=0.033), and a higher rate of
mutations (18%
4%, p=0.084).
alterations were not associated with any occupational carcinogens. The DEF-exposed patients were diagnosed with a
mutation in 25% of all cases. Chrome-exposed patients exhibited enhanced
and
mutation frequency.Given its minimal effects in the subgroups, we conclude that occupational exposure slightly affects the molecular pattern of lung cancers in never-smokers. In particular, asbestos-exposed patients have a lower chance of
mutations.
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