Randomised controlled trial of first-line tyrosine-kinase inhibitor (TKI) versus intercalated TKI with chemotherapy for EGFR-mutated nonsmall cell lung cancer

Introduction Previous studies have shown interference between epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors and chemotherapy in the cell cycle, thus reducing efficacy. In this randomised controlled trial we investigated whether intercalated erlotinib with chemotherapy was superior compared to erlotinib alone in untreated advanced EGFR-mutated nonsmall cell lung cancer (NSCLC). Materials and methods Treatment-naïve patients with an activating EGFR mutation, ECOG performance score of 0–3 and adequate organ function were randomly assigned 1:1 to either four cycles of cisplatin-pemetrexed with intercalated erlotinib (day 2–16 out of 21 days per cycle) followed by pemetrexed and erlotinib maintenance (CPE) or erlotinib monotherapy. The primary end-point was progression-free survival (PFS). Secondary end-points were overall survival, objective response rate (ORR) and toxicity. Results Between April 2014 and September 2016, 22 patients were randomised equally into both arms; the study was stopped due to slow accrual. Median follow-up was 64 months. Median PFS was 13.7 months (95% CI 5.2–18.8) for CPE and 10.3 months (95% CI 7.1–15.5; hazard ratio (HR) 0.62, 95% CI 0.25–1.57) for erlotinib monotherapy; when compensating for number of days receiving erlotinib, PFS of the CPE arm was superior (HR 0.24, 95% CI 0.07–0.83; p=0.02). ORR was 64% for CPE versus 55% for erlotinib monotherapy. Median overall survival was 31.7 months (95% CI 21.8–61.9 months) for CPE compared to 17.2 months (95% CI 11.5–45.5 months) for erlotinib monotherapy (HR 0.58, 95% CI 0.22–1.41 months). Patients treated with CPE had higher rates of treatment-related fatigue, anorexia, weight loss and renal toxicity. Conclusion Intercalating erlotinib with cisplatin-pemetrexed provides a longer PFS compared to erlotinib alone in EGFR-mutated NSCLC at the expense of more toxicity

A randomised cross-over trial investigating the ease of use and preference of two dry powder inhalers in patients with asthma ofr chronic obstructive pulmonary disease

Objectives: The objective of this randomised, cross-over study was to compare a new single-dose dry powder inhaler (Elpenhaler (EH)), with a widely used, multi-dose dry powder inhaler (Diskus (DK)) on critical errors, patient preference, and satisfaction with the inhalers. Methods: First, patients read the instructions of one device, followed by a first inhalation attempt. Inhalation errors were assessed and if mistakes were made, correct inhaler use was demonstrated. Then patients had to demonstrate again and mistakes were registered. This was repeated up to four times. After completing the first device, the same procedure was started with the second inhaler. Primary outcome was the percentage of patients making at least one critical error after reading the insert. Secondary outcomes were inhaler preference and satisfaction with the inhalers. Results: After reading the insert, 19 of 113 patients (17%) made at least one critical error with DK and 40 (35%) with EH (p = 0.001); 73% preferred the DK and 27% the EH (p < 0.001). The mean overall satisfaction score (1 = very satisfied; 5 = very dissatisfied) for DK was 1.59 and for EH 2.48 (p < 0.001). Conclusion: With DK fewer errors were made, more patients preferred DK over EH and patients were more satisfied with DK. This may enable DK to improve treatment outcomes more than EH

Preference, satisfaction and errors with two dry powder inhalers in patients with COPD

Objective: To assess preference, satisfaction and critical errors with a novel, breath-actuated, multi-dose dry powder inhaler (DPI; Genuair®/Pressair™), versus a widely used, single-dose DPI (HandiHaler®) in patients with moderate-to-severe chronic obstructive pulmonary disease. Methods: In this randomised, open-label, multicentre, cross-over study, patients (aged ≥ 40 years) inhaled placebo once daily through both inhalers for 2 weeks in addition to current medication. The primary end point was percentage of patients who preferred Genuair to HandiHaler. Overall patient satisfaction (5-point scale: 1 = very dissatisfied; 5 = very satisfied), critical errors and willingness to continue using each inhaler (0 = not willing; 100 = definitely willing) were assessed. Results: Of 130 patients randomised, 105 were included in the intent-to-treat population (71.4% male; mean age 65.7 years). After 2 weeks, significantly more patients preferred Genuair than HandiHaler (79.1 vs 20.9%; p < 0.0001). Overall satisfaction scores (4.6 vs 3.8; p < 0.0001) and willingness to continue use scores (84.0 vs 62.5; p < 0.0001) were significantly higher with Genuair versus HandiHaler. Significantly fewer patients made ≥ 1 critical error with Genuair only compared with HandiHaler only (2.9 vs 19.0%; p < 0.0001). Conclusion: After 2 weeks' practice, patients preferred and were more willing to continue using Genuair than HandiHaler. Genuair was associated with higher patient satisfaction and fewer critical errors than HandiHaler Read More: http://informahealthcare.com/doi/abs/10.1517/17425247.2013.80818

A randomised open-label cross-over study of inhaler errors, preference and time to achieve correct inhaler use in patients with COPD or asthma: Comparison of ELLIPTA with other inhaler devices

Errors in the use of different inhalers were investigated in patients naive to the devices under investigation in a multicentre, single-visit, randomised, open-label, cross-over study. Patients with chronic obstructive pulmonary disease (COPD) or asthma were assigned to ELLIPTA vs DISKUS (Accuhaler), metered-dose inhaler (MDI) or Turbuhaler. Patients with COPD were also assigned to ELLIPTA vs Handihaler or Breezhaler. Patients demonstrated inhaler use after reading the patient information leaflet (PIL). A trained investigator assessed critical errors (i.e., those likely to result in the inhalation of significantly reduced, minimal or no medication). If the patient made errors, the investigator demonstrated the correct use of the inhaler, and the patient demonstrated inhaler use again. Fewer COPD patients made critical errors with ELLIPTA after reading the PIL vs: DISKUS, 9/171 (5%) vs 75/171 (44%); MDI, 10/80 (13%) vs 48/80 (60%); Turbuhaler, 8/100 (8%) vs 44/100 (44%); Handihaler, 17/118 (14%) vs 57/118 (48%); Breezhaler, 13/98 (13%) vs 45/98 (46%; all P<0.001). Most patients (57-70%) made no errors using ELLIPTA and did not require investigator instruction. Instruction was required for DISKUS (65%), MDI (85%), Turbuhaler (71%), Handihaler (62%) and Breezhaler (56%). Fewer asthma patients made critical errors with ELLIPTA after reading the PIL vs: DISKUS (3/70 (4%) vs 9/70 (13%), P=0.221); MDI (2/32 (6%) vs 8/32 (25%), P=0.074) and significantly fewer vs Turbuhaler (3/60 (5%) vs 20/60 (33%), P<0.001). More asthma and COPD patients preferred ELLIPTA over the other devices (all P≤0.002). Significantly, fewer COPD patients using ELLIPTA made critical errors after reading the PIL vs other inhalers. More asthma and COPD patients preferred ELLIPTA over comparator inhalers

Comparison of clinical outcome after first-line platinum-based chemotherapy in different types of KRAS mutated advanced non-small-cell lung cancer

Objectives: As suggested by in-vitro data, we hypothesize that subtypes of ICRAS mutated non-small cell lung cancer (NSCLC) respond differently to chemotherapy regimens. Methods: Patients with advanced NSCLC and known KRAS mutation, treated with first-line platinumbased chemotherapy, were retrieved from hospital databases. Primary objective: to investigate overall response rate (ORR), progression free survival (PFS) and overall survival (OS) between different types of platinum-based chemotherapy per type of KRAS mutation. Results: 464 patients from 17 hospitals, treated between 2000 and 2013, were included. The majority of patients had stage IV disease (93%), had a history of smoking (98%) and known with an adenocarcinoma (91%). Most common types of ICRAS mutation were G12C (46%), G12V (20%) and G1 2D (10%). Platinum was combined with pemetrexed (n =334), taxanes (n = 68) or gemcitabine (n = 62). Patients treated with taxanes had a significant improved ORR (50%) compared to pemetrexed (21%) or gemcitabine (25%; p <0.01). Patients treated with bevacizumab in addition to taxanes (n =38) had the highest ORR (62%). The PFS was significantly improved in patients treated with taxanes compared to pemetrexed (HR = 0.72, p = 0.02), but not OS (HR= 0.87, p = 0.41). In patients with G12V, significantly improved ORR (p <0.01) was observed for taxanes, but not PFS or OS. Patients with G1 2C or G12D mutation had comparable ORR, PFS and OS in all treatment groups. Conclusion: KRAS mutated NSCLC patients treated with taxane-based chemotherapy had best ORR Response to chemotherapy regimens was different in types of ICRAS mutation. Especially patients with G12V had better response to taxane treatment. (C) 2015 Elsevier Ireland Ltd. All rights reserved

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