Neuropsychological assessment fails to predict relapse among cigarette smokers: A prospective study of neurocognitive abilities.

OBJECTIVES: Understanding the factors that lead to relapse is a major challenge for the clinical support of smoking cessation. Neurocognitive abilities such as attention, executive functioning and working memory, are possible predictors of relapse and can be easily assessed in everyday clinical practice. In this prospective longitudinal study, we investigated the relationship between pre-smoking cessation neurocognitive performance and relapse at six months in a sample of patients being treated for their tobacco dependence. METHODS: 130 tobacco consumers were included in the study. They completed a comprehensive neuropsychological and clinical assessment before smoking cessation. The targeted abilities were intelligence, inhibition, shifting, working memory updating, verbal fluency and decision-making. RESULTS: The rate of tobacco relapse at 6 months was 58%. Logistic regressions were used to assess which variables best explained relapse. None of the neuropsychological tests was a significant predictor of relapse at either 1, 3 or 6 months, either alone, or controlling for other covariates acting as significant predictors of relapse. CONCLUSIONS: Common neuropsychological tests, even those specifically targeting executive functioning such as inhibition, are not useful predictors of the success of a smoking cessation program in a clinical setting. Other variables, such as motivation to quit smoking or the presence of comorbid depression or anxiety disorders, appear to be more useful predictors of relapse.

Enrolment of older adults with advanced or metastatic non-small cell lung cancer in first-line clinical trials in the multicentre ESME cohort.

INTRODUCTION: There is a great need for data based on clinical trials for the older population in order to improve treatment. Historically, the inclusion rate of older adults in clinical trials has been low, but the rate specific to lung cancer is unknown, as are the factors associated with enrolment. MATERIALS AND METHODS: We used the national Epidemio-Strategy and Medical Economics Advanced or Metastatic Lung Cancer (AMLC) Data Platform, a multicentre real-life database. Inclusion criteria were patients with advanced or metastatic non-small cell lung cancer (AMNSCLC) aged 70 years or older, with at least one line of systemic treatment from 01 January 2015 to 31 December 2018. The primary objective was to evaluate the proportion of older adults enrolled in clinical trials. Secondary objectives were to identify factors associated with enrolment in clinical trials for older patients and to compare the overall survival of older adults included in trials versus those not included. RESULTS: There were 3488 patients aged ≥70 years (median age at AMNSCLC 75 years). Among older patients, 234 (6.7%) were enrolled in a clinical trial in the first-line setting. Significant factors associated with enrolment in the multivariable analysis in older patients were: good Eastern Cooperative Oncology Group (ECOG) Performance Status (PS 0) (p < 0.001), de novo versus recurrent presentation at diagnosis (p < 0.001), and non-central nervous system (CNS) metastases versus advanced setting or CNS metastases (p < 0.001). Medical history was associated with fewer inclusions (odds ratio [OR] = 0.74, 95% confidence interval [CI] [0.56; 0.99]). Among older patients, being enrolled in a trial in the first-line setting was not associated with better overall survival (OS) (hazard ratio [HR] = 1.03; 95%CI 0.86-1.22) in the multivariable analysis. DISCUSSION: In this large database, few older AMNSCLC patients were enrolled in a trial. Factors associated with enrolment were: good ECOG PS, absence of medical history, de novo AMNSCLC, and presentation with non-CNS metastases.

Impact of immune checkpoint inhibitors on the management of locally advanced or metastatic non-small cell lung cancer in real-life practice in patients initiating treatment between 2015 and 2018 in France and Germany.

OBJECTIVES: To describe the impact of immune checkpoint inhibitors (ICIs) on treatment patterns and survival outcomes in patients with locally advanced or metastatic non-small cell lung cancer (aNSCLC) in France and Germany. MATERIALS AND METHODS: Patients with aNSCLC without known ALK or EGFR mutations receiving first-line (1L) therapy were included from (i) the retrospective Epidemiological-Strategy and Medical Economics Advanced and Metastatic Lung Cancer cohort (ESME-AMLC, France; 2015-2018) and (ii) the prospective Clinical Research platform Into molecular testing, treatment and outcome of non-Small cell lung carcinoma Patients platform (CRISP, Germany; 2016-2018). Analyses were stratified according to histology. Survival outcomes were estimated using Kaplan-Meier methodology and stratified by year of 1L therapy. Data sources were analysed separately. RESULTS: In ESME-AMLC and CRISP, 8,046 and 2,359 patients were included in the study, respectively. In both countries, approximately 20 % of all patients received pembrolizumab monotherapy as 1L treatment in 2018. In ESME-AMLC, the proportion receiving an ICI over the course of treatment (any line) increased from 42.2 % (2015) to 56.1 % (2018) in patients with squamous histology, and 28.9 % to 51.9 % with non-squamous/other; in CRISP, it increased from 50.6 % (2016) to 65.2 % (2018) with squamous histology, and 40.8 % to 62.7 % with non-squamous/other. Two-year overall survival from 1L initiation was 36.8 % and 25.6 % in the squamous cohorts and 36.5 % and 30.8 % in the non-squamous/other cohorts in ESME-AMLC and CRISP, respectively. No significant change in overall survival was observed over time; however, the follow-up time available was limited in the later years of the analysis. CONCLUSION: The results of this joint research from two large clinical databases in France and Germany demonstrate the growing use of ICIs in the management of aNSCLC. Future analyses will allow for the evaluation of the impact of ICIs on long-term survival of patients with aNSCLC.

Treatment strategies for unresectable locally advanced non-small cell lung cancer in the real-life ESME cohort.

BACKGROUND: Cisplatin-based chemotherapy administered concurrently to thoracic radiation therapy is the recommended treatment for fit patients with unresectable stage III NSCLC. The aim of this study was to describe patient profiles and clinical outcomes for the different treatment strategies in a real-word setting. METHODS: The epidemio-strategy and medical economics (ESME) database for advanced and metastatic lung cancer is a French, national, multicenter, observational cohort. Out of 8514 Patients, 822 patients with unresectable locally advanced NSCLC in 2015-016 were selected (mean age, 65.3 years; male gender, 69%; performance status 0-1, 77%; smokers or former smokers, 89%). RESULTS: Treatment was initiated for 736 (90%) of patients (concurrent chemoradiotherapy, n = 283; sequential chemoradiotherapy, n = 121; chemotherapy alone, n = 194; radiotherapy alone, n = 121; targeted therapy alone, n = 8; other, n = 9). Compared to the other treatment strategy groups, patients with radiotherapy alone appeared the most fragile (e.g. higher age, lower body weight or higher frequency of chronic obstructive pulmonary disease). OS rates at 12 and 24 months were 79.5% (95% CI, 73.4-84.3) and 55.3% (95% CI, 44.9-64.5) for concurrent chemoradiotherapy, and 64.3% (95% CI, 52.8-73.8) and 53.2 (95% CI, 33.2-69.6) for sequential chemoradiotherapy. CONCLUSIONS: Real-world evidence shows that concurrent chemoradiotherapy is administered to the most fit patients with non resectable locally-advanced NSCLC. Clinical outcomes are actually higher than those reported in landmark clinical trials, which suggests that an optimized and individualized selection of patients allows for prolonged survival. Long-term outcomes are similar after sequential or concurrent chemoradiotherapy.

A Real-World Study of Patients with Advanced Non-squamous Non-small Cell Lung Cancer with EGFR Exon 20 Insertion: Clinical Characteristics and Outcomes.

BACKGROUND: In Europe, few data regarding the characteristics of EGFR exon 20 insertion (20ins) mutations in non-small cell lung cancer (NSCLC) are available. OBJECTIVE: Using a large real-world cohort, we assessed the incidence, characteristics, and outcomes of patients with non-squamous (nsq) NSCLC harboring EGFR exon 20ins. PATIENTS AND METHODS: The Epidemio-Strategy and Medical Economics advanced and metastatic lung cancer data platform including advanced/metastatic nsqNSCLC patients from January 2015 was analyzed (cut-off date: June 30, 2020). Characteristics, epidermal growth factor receptor (EGFR) mutation and other mutations, treatment patterns, and clinical outcomes were assessed for patients harboring EGFR exon 20ins, common EGFR mutations, other EGFR mutations, and wild-type EGFR. Survival parameters were estimated by the Kaplan-Meier method in these four groups. RESULTS: Out of 9435 nsqNSCLC patients tested for EGFR, 1549 (16.4%) had a mutation, including 61 with EGFR exon 20ins (3.9% of all mutated EGFR). These 61 patients had a mean age of 63.6 years, were mostly female (68.9%) and non-smokers (55.7%), with de novo stage IV disease (73.8%) and performance status 0-1 (76.9%). Almost all patients (95.1%) with exon 20ins received systemic therapy (median, three lines). First-line systemic treatments consisted mainly of combination chemotherapy (70.7%), single-agent EGFR tyrosine kinase inhibitors (10.3%), and single-agent immunotherapy (5.2%). After a median follow-up of 25.0 (95% confidence interval [CI] 22.3-32.4) months, the median real-world overall survival was 24.3 (19.1-32.6) months in patients with exon 20ins compared to 35.4 (95% CI 32.6-37.5) in patients with common EGFR mutation (n = 1049) (p = 0.049) and 19.6 (95% CI 18.6-20.5) in patients with wild-type EGFR (n = 7866) (p = 0.2). CONCLUSIONS: This large national study in nsqNSCLC patients confirms that EGFR exon 20ins is a rare condition (0.6%). The prognosis associated with exon 20ins appears to be in line with that of wild-type EGFR, but worse than common EGFR mutations, highlighting the need for advancements for this rare population.

Biomarker Testing in Older Patients Treated for an Advanced or Metastatic Non-Squamous Non-Small-Cell Lung Cancer: The French ESME Real-Life Multicenter Cohort Experience.

BACKGROUND: Genomic and immunologic tumor biomarker testing has dramatically changed the prognosis of patients, particularly those treated for advanced/metastatic non-squamous non-small-cell lung cancer (aNSCLC) when access to targeted agents is available. It remains unclear whether older patients have access to therapy-predictive biomarker testing techniques in the same proportion as younger patients. This study aims to compare the proportion of biomarker testing performed in non-squamous aNSCLC at diagnosis between patients aged ≥70 years old and their younger counterparts. METHODS: We conducted a retrospective analysis using the Epidemio-Strategy and Medical Economics (ESME) Advanced or Metastatic Lung Cancer Data Platform, a French multicenter real-life database. All patients with non-squamous aNSCLC diagnosed between 2015 and 2018 were selected. Biomarker testing corresponded to at least one molecular alteration and/or PD-L1 testing performed within 1 month before or 3 months after the aNSCLC diagnosis. RESULTS: In total, 2848 patients aged ≥70 years and 6900 patients aged <70 years were included. Most patients were male. The proportion of current smokers at diagnosis was higher in the <70 years group (42% vs. 17%, p < 0.0001). There was no significant difference in the proportion of biomarker testing performed between the two groups (63% vs. 65%, p = 0.15). EGFR mutations were significantly more common in the older group (22% vs. 12%, p < 0.0001) and KRAS mutations significantly more frequent in the younger group (39% vs. 31% p < 0.0001). The distribution of other driver mutations (ALK, ROS1, BRAF V600E, HER2, and MET) was similar across age. In the multivariable analysis, factors independently associated with biomarker testing were gender, smoking status, history of COPD, stage at primary diagnosis, and histological type. CONCLUSIONS: Age is not a barrier to biomarker testing in patients with aNSCLC.

Clinical efficacy and cost-effectiveness of endobronchial ultrasound-guided transbronchial needle aspiration for preoperative staging of non-small-cell lung cancer: Results of a French prospective multicenter trial (EVIEPEB).

This two-step study evaluated the cost-effectiveness of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) for presurgery staging of non-small cell lung cancer (NSCLC) in France (EVIEPEB; ClinicalTrial.gov identifier NCT00960271). Step 1 consisted of a high-benchmark EBUS-TBNA-training program in participating hospital centers. Step 2 was a prospective, national, multicenter study on patients with confirmed or suspected NSCLC and an indication for mediastinal staging with at least one lymph node > 1 cm in diameter. Patients with negative or uninformative EBUS-TBNA and positron-emission tomography-positive or -negative nodes, respectively, underwent either mediastinoscopy or surgery. Direct costs related to final diagnosis of node status were prospectively recorded. Sixteen of 22 participating centers were certified by the EBUS-TBNA-training program and enrolled 163 patients in Step 2. EBUS-TBNA was informative for 149 (91%) patients (75 malignant, 74 non-malignant) and uninformative for 14 (9%). Mediastinoscopy was avoided for 80% of the patients. With a 52% malignant-node rate, EBUS-TBNA positive- and negative-predictive values, respectively, were 100% and 90%. EBUS-TBNA was cost-effective, with expected savings of €1,450 per patient, and would have remained cost-effective even if all EBUS-TBNAs had been performed under general anesthesia or the cost of the procedure had been 30% higher (expected cost-saving of €994 and €1,427 per patient, respectively). After EBUS-TBNA training and certification of participating centers, the results of this prospective multicenter study confirmed EBUS-TBNA cost-effectiveness for NSCLC staging.