Search

Aim: Investigate the effectiveness of chemotherapy for first-line (1L) treatment of metastatic bladder cancer (mBC). Methods: Retrospective cohort study evaluating treatment patterns/outcomes in 1155 mBC patients receiving initial treatment in the community practice setting from January 2010 to June 2014, and followed through July 2016. Results: The most commonly utilized 1L and second-line (2L) regimens were platinum-based and taxane-based, respectively. Median (95% CI) OS for all patients from 1L initiation was 12.8 months (11.7-14.6), and median OS for all 2L regimens was 9.4 months (8.2-11.1). Conclusion: mBC patients eligible for and who received cis-based regimens experienced better OS results. Poor renal function was a key driver of cis-ineligibility. The various monotherapy and combination chemotherapy regimens in 2L produced relatively short OS outcomes.

Aim: Cetuximab was approved in 2008 for treating recurrent/metastatic (R/M) head-and-neck squamous-cell carcinoma (HNSCC), and this study assessed the utilization of cetuximab for R/M-HNSCC in a real-world setting., Materials & Methods: Adult patients with R/M-HNSCC, who initiated systemic therapy between 1 September 2011 and 31 December 2014 and followed through 31 December 2015, were identified from iKnowMed electronic-health-records database (McKesson Specialty Health) supplemented with manual chart-abstraction., Results: For 325 R/M-HNSCC patients; median age 62 years; 82% males, 67% had oropharyngeal cancer, most common first-line (1L) regimen was platinum-based combinations (76%), of whom only 8% received platinum + cetuximab +/- 5-fluorouracil., Conclusion: Despite US FDA approval and National Comprehensive Cancer Network guidelines recommending use of cetuximab for palliative treatment of R/M-HNSCC, our study demonstrates low utilization in 1L and 2L settings, underscoring the need to understand reasons for low utilization.

Introduction: Around 3⁻5% of non-small cell lung cancers (NSCLC) are ALK-positive. Crizotinib was the first approved ALK inhibitor from clinical trials. However, there are less data on the utilization and patient outcomes associated with crizotinib in real-world clinical practice., Methods: This was a retrospective, observational study of adult crizotinib-treated ALK-positive metastatic NSCLC patients who received treatment between 1 September 2011 and 31 October 2014, with follow up through 31 December 2015. Data were obtained via programmatic queries of the US Oncology Network/McKesson Specialty Health electronic health record database, supplemented with chart abstraction. Overall survival (OS) and time to treatment failure (TTF) were estimated from crizotinib initiation using the Kaplan⁻Meier (KM) method., Results: Of the n = 199 ALK-positive crizotinib-treated patients meeting eligibility criteria, crizotinib was prescribed as first line (1 L) in n = 123 (61.8%). The majority (88.9%) had confirmed adenocarcinoma histology and 32.2% had brain metastases at initial diagnosis. Median age at crizotinib initiation was 60.2 years (range 27.1⁻88.2); 54.8% were never smokers, 33.7% were former smokers. Treatment of 250 mg, twice daily, was most commonly prescribed (89.5%) with the dose unchanged from an initial dose in 79.4% of patients. The primary discontinuation reason was progression ( n = 91, 58.7%). Patients (3.2%) were identified as discontinuing crizotinib as a result of treatment-related toxicity. With median follow-up time of 13.0 months (min⁻max = 0.03⁻46.6), median OS from crizotinib initiation was 33.8 months (95% CI = 24.3⁻38.8). Median TTF was 10.4 months., Conclusions: Crizotinib usage evaluated within the real-world setting is consistent with prior phase III clinical trial data, and illustrates the real-world effectiveness of crizotinib.

The programmed death-1 inhibitor pembrolizumab has demonstrated efficacy and safety in clinical trials for treating advanced (unresectable/metastatic) melanoma. We investigated the real-world utilization of pembrolizumab and associated patient outcomes for advanced melanoma in US community oncology practices. This retrospective, observational study used deidentified data from electronic health records for adult patients with advanced melanoma who received pembrolizumab at The US Oncology Network sites from September 2014 through December 2015, with follow-up through September 2016. Patients enrolled in clinical trials were excluded. Overall survival (OS) and physician-stated progression-free survival (PFS) were analyzed from pembrolizumab initiation using Kaplan-Meier, and associations between pembrolizumab therapy and OS/PFS, using multivariable Cox regression. Of 168 patients studied, 110 (65%) were male; the median age was 66 years (range, 26-over 90). Pembrolizumab was prescribed as first-line, second-line, and third-line/later for 39 (23%), 87 (52%), and 42 (25%) patients, respectively. In total, 41 patients (24%) had brain metastases. At pembrolizumab initiation, 21/129 (16%) had Eastern Cooperative Oncology Group performance status (ECOG PS) >1; 51/116 (44%) had elevated lactate dehydrogenase. Median follow-up was 10.5 months (range, 0-25.1); median OS was 19.4 months (95% confidence interval, 14.0-not reached); median PFS was 4.2 months (95% confidence interval, 2.9-5.3). Brain metastases, ECOG PS>1, elevated lactate dehydrogenase, and third-line/later (vs. first-line) pembrolizumab were significant predictors (P<0.01) of decreased survival. Treatment-related toxicity was a discontinuation reason for 25% (29/117) of patients, and for 10 of these 29 patients (6% of the full-study cohort) treatment-related toxicity was the only reported reason. The real-world effectiveness and safety of pembrolizumab for advanced melanoma are consistent with clinical trial findings.

Rationale: Chronic bronchitis is, by definition, a chronic condition, but the development and remission of this condition in cigarette smokers with or without chronic obstructive pulmonary disease (COPD) are poorly understood. Also, it is unclear how the persistence or new development of chronic bronchitis affects symptoms and outcomes., Objectives: To ascertain the relationship between smoking status and the presence or absence of chronic bronchitis and the subsequent effects on symptoms and outcomes., Methods: We analyzed 1,775 current or ex-smokers with GOLD (Global Initiative for Chronic Obstructive Lung Disease) stage 0-IV COPD in phase 2 of the Genetic Epidemiology of COPD (COPDGene) Study, which included subjects after 5 years of follow-up from phase 1. We asked subjects at enrollment and at 5 years of follow-up about symptoms consistent with chronic bronchitis. We divided subjects into four groups: persistent chronic bronchitis- (negative at phase 1/negative at phase 2), resolved chronic bronchitis (positive/negative), new chronic bronchitis (negative/positive), and persistent chronic bronchitis+ (positive/positive). We analyzed respiratory symptoms, health-related quality of life, lung function, exacerbation frequency, and 6-minute walk distance., Measurements and Main Results: Compared with the persistent chronic bronchitis- group, members of the persistent chronic bronchitis+ group were more likely to have continued smoking (53.4%). Subjects with new chronic bronchitis were more likely to have resumed (6.6%) or continued smoking (45.6%), whereas subjects with resolved chronic bronchitis were more likely to have quit smoking (23.5%). Compared with the persistent chronic bronchitis- group, the other groups had a shorter 6-minute walk distance, worse lung function, greater exacerbation frequency, and worse respiratory symptoms. Modified Medical Research Council dyspnea and St. George's Respiratory Questionnaire scores worsened between phase 1 and phase 2 in subjects with new chronic bronchitis but improved in the resolved chronic bronchitis group. On multinomial logistic regression, quitting smoking conferred an odds ratio (OR) of 4.289 (95% confidence interval [CI], 2.689-6.842) for resolved chronic bronchitis, whereas resuming smoking had an OR of 4.585 (95% CI, 2.008-10.471) for new chronic bronchitis. Persistent smoking had an OR of 2.621 (95% CI, 1.677-4.096) and 5.767 (95% CI, 3.702-8.983) for subjects with new chronic bronchitis and subjects with persistent chronic bronchitis, respectively., Conclusions: Persistent and newly developed chronic bronchitis are associated with continued or resumed smoking, greater respiratory symptoms, worse health-related quality of life, worse lung function, and greater exacerbation frequency. These findings stress the importance of repeatedly assessing chronic cough and sputum production in smokers to identify those at risk for poor outcomes.

Background: Whether African Americans (AA) are more susceptible to COPD than non-Hispanic Whites (NHW) and whether racial differences in disease phenotype exist is controversial. The objective is to determine racial differences in the extent of emphysema and airway remodeling in COPD., Methods: First, 2,500 subjects enrolled in the COPDGene study were used to evaluate racial differences in quantitative CT (QCT) parameters of% emphysema, air trapping and airway wall thickness. Independent variables studied included race, age, gender, education, BMI, pack-years, smoking status, age at smoking initiation, asthma, previous work in dusty job, CT scanner and center of recruitment., Results: Of the 1,063 subjects with GOLD Stage II-IV COPD, 200 self-reported as AA. AAs had a lower mean% emphysema (13.1% vs. 16.1%, p = 0.005) than NHW and proportionately less emphysema in the lower lung zones. After adjustment for covariates, there was no statistical difference by race in air trapping or airway wall thickness. Measured QCT parameters were more predictive of poor functional status in NHWs compared to AAs., Conclusions: AAs have less emphysema than NHWs but the same degree of airway disease. Additional factors not easily assessed by current QCT techniques may account for the poor functional status in AAs.

Objective: Coronary artery calcification (CAC) and thoracic aortic calcification, (TAC) are frequently detected on ungated multidetector computed tomography (MDCT) performed for lung evaluations. We sought to evaluate concordance of CAC and TAC scores on ungated (thoracic) and electrocardiogaphically (ECG)-gated (cardiac) MDCT scans., Methods: Fifty patients, enrolled in the Genetic Epidemiology of COPD study (COPDGene), were recruited to undergo gated CAC scans with 64-detector row CT, in addition to the ungated thoracic studies already being obtained as part of their study evaluation. Coronary and thoracic calcium were measured similarly (Agatston score, requiring 3 contiguous voxels of >130 Hounsfield units) with low-dose ungated studies and ECG-gated MDCT performed at the same scanning session. Intertechnique scoring variability and concordance were calculated., Results: Correlations between gated and ungated CAC and TAC were excellent (r = 0.96). The relative differences (median variability) measured by ECG-gated versus ungated MDCT were relatively high for CAC (44%) but not for TAC (8%). Prevalence of depicted CAC (n = 33; 66%) and TAC (n = 21; 42%) were coincident between ECG-gated and ungated MDCT, respectively (intertechnique concordance, 100%). Bland-Altman plots for CAC showed mean differences of 354 (confidence interval, 169-538) and 16.1 (confidence interval, -89 to 121)., Conclusion: Low-dose ungated MDCT is reliable for prediction of the presence of CAC and assessment of Agatston score. Concordance between methods and between TAC and CAC is high. This technique should allow for atherosclerotic disease risk stratification among patients undergoing ungated lung CT evaluation without requiring additional scanning. Measurement of TAC is almost as accurate from gated CT, and CAC scores are highly concordant., (Copyright © 2011 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.)