Phase II study of durvalumab plus tremelimumab as therapy for patients with previously treated anti-PD-1/PD-L1 resistant stage IV squamous cell lung cancer (Lung-MAP substudy S1400F, NCT03373760)

INTRODUCTION: S1400F is a non-match substudy of Lung Cancer Master Protocol (Lung-MAP) evaluating the immunotherapy combination of durvalumab and tremelimumab to overcome resistance to anti-programmed death ligand 1 (PD-(L)1) therapy in patients with advanced squamous lung carcinoma (sq non-small-cell lung cancer (NSCLC)). METHODS: Patients with previously treated sqNSCLC with disease progression after anti-PD-(L)1 monotherapy, who did not qualify for any active molecularly targeted Lung-MAP substudies, were eligible. Patients received tremelimumab 75 mg plus durvalumab 1500 mg once every 28 days for four cycles then durvalumab alone every 28 days until disease progression. The primary endpoint was the objective response rate (RECIST V.1.1). Primary and acquired resistance cohorts, defined as disease progression within 24 weeks versus ≥24 weeks of starting prior anti-PD-(L)1 therapy, were analyzed separately and an interim analysis for futility was planned after 20 patients in each cohort were evaluable for response. RESULTS: A total of 58 eligible patients received drug, 28 with primary resistance and 30 with acquired resistance to anti-PD-(L)1 monotherapy. Grade ≥3 adverse events at least possibly related to treatment were seen in 20 (34%) patients. The response rate in the primary resistance cohort was 7% (95% CI 0% to 17%), with one complete and one partial response. No responses were seen in the acquired resistance cohort. In the primary and resistance cohorts the median progression-free survival was 2.0 months (95% CI 1.6 to 3.0) and 2.1 months (95% CI 1.6 to 3.2), respectively, and overall survival was 7.7 months (95% CI 4.0 to 12.0) and 7.6 months (95% CI 5.3 to 10.2), respectively. CONCLUSION: Durvalumab plus tremelimumab had minimal activity in patients with advanced sqNSCLC progressing on prior anti-PD-1 therapy

Ancillary Testing in Lung Cancer Diagnosis

The pathologic diagnosis of lung cancer historically has relied primarily on morphologic features of tumors in histologic sections. With the emergence of new targeted therapies, the pathologist is called upon increasingly to provide not only accurate typing of lung cancers, but also to provide prognostic and predictive information, based on a growing number of ancillary tests, that may have significant impact on patient management. This review provides an overview of ancillary tests currently used in the pathologic diagnosis of lung cancer, with a focus on immunohistochemistry and molecular diagnostics

PCN162 The Cost-Effectiveness of Second-Line Crizotinib in Eml4-Alk Rearranged Advanced Non-Small Cell Lung Cancer

Background: Snoring / sleep apnea are potentially life threatening breathing occurs during sleep. Little attention is being giving to this clinical condition. Objective: To determine the prevalence of snoring and risk factors associated with obstructive sleep apnea (OSA) among adults workers in two local governments of state, Nigeria Methodology: A cross - sectional survey of 121 young adult and adults working in two local governments of Ekiti state, south western Nigeria was carried out. A self administered questionnaire that was incorporated with Epworth Sleepiness Scale and Berlin Score was used to collect data on socio-demographic characteristics, information related to snoring, sleep related problems and their anthropometric. The Body Mass Index (BMI) and blood pressure of each participant were also measured. Results: Snoring was reported in forty nine (40.5%) of the participants. Their age ranges from 23 to 65 years, mean of 43.89 ± 8.53 SD. The proportion of males and Berlin score (high risk) were significantly (p < 0.001) higher among snores than non regression found sex (OR=7.791, 95% CI =2.971- 20.429), Berlin Score (high risk) (OR= 8.642, 95% CI= 3.159 - 23.639) as significant (P< 0.001) independent risk factors for OSA. Excessive day time sleepiness as determined by ESS score of the participants. Conclusion: The overall prevalence of snoring in this study was 40.5%. Snoring was found to increase with age, body mass index, male sex and those with high risk for Berlin score with high risk of developing Obstructive sleep apne

Challenges to Implementation of an Epidermal Growth Factor Receptor Testing Strategy for Non–Small-Cell Lung Cancer in a Publicly Funded Health Care System

Background:Data from seven recent randomized clinical trials have demonstrated that epidermal growth factor (EGFR) mutation status is predictive of improved progression-free survival and quality of life from first-line EGFR tyrosine kinase inhibitor therapy compared with platinum-based chemotherapy. We examined barriers to the initial implementation of a national EGFR testing policy in Canada.Methods:Five laboratories across Canada underwent a validation and quality-control exercise for EGFR mutation testing using reverse transcriptase–polymerase chain reaction with financial support from the pharmaceutical industry for the initial 12 months. Oncologists registered patients with nonquamous histology for EGFR mutation testing using a Web-based platform. Basic demographics were collected including age, histology, sex, smoking status, and ethnicity. The decision to prescribe gefitinib was subsequently registered on the system.Results:Between March and December 2010, 2104 requests were received for EGFR mutation testing. Demographic details are as follows: adenocarcinoma (91.6%); Asian ethnicity (13.9%); female (58%); light/never smoker (41.3%); stage IV disease (87.1%). The number of tests requested each month ranged from 200 to 250. Mutation testing was conducted in 1771 of 2104 requests (84%). The median turnaround time for EGFR testing was 18 days (standard deviation 9.7). Gefitinib was prescribed in 302 patients (17.1%). The number of test requests dropped to 50 to 100 per month at the end of the initial 12 months.Conclusion:There was rapid uptake of EGFR mutation testing into routine clinical practice in Canada. Uptake of EGFR mutation testing dropped substantially once funding from pharmaceutical industry was discontinued. There is a need for a national strategy to ensure resources are in place to implement molecular testing for new molecularly targeted agents

Advantages of the net benefit regression framework for trial-based economic evaluations of cancer treatments: an example from the Canadian Cancer Trials Group CO.17 trial.

BackgroundEconomic evaluations commonly accompany trials of new treatments or interventions; however, regression methods and their corresponding advantages for the analysis of cost-effectiveness data are not widely appreciated.MethodsTo illustrate regression-based economic evaluation, we review a cost-effectiveness analysis conducted by the Canadian Cancer Trials Group's Committee on Economic Analysis and implement net benefit regression.ResultsNet benefit regression offers a simple option for cost-effectiveness analyses of person-level data. By placing economic evaluation in a regression framework, regression-based techniques can facilitate the analysis and provide simple solutions to commonly encountered challenges (e.g., the need to adjust for potential confounders, identify key patient subgroups, and/or summarize "challenging" findings, like when a more effective regimen has the potential to be cost-saving).ConclusionsEconomic evaluations of patient-level data (e.g., from a clinical trial) can use net benefit regression to facilitate analysis and enhance results

Cancer patient preferences for communication of prognosis in the metastatic setting

PURPOSE: To identify preferences for and predictors of prognostic information among patients with incurable metastatic cancer. PATIENTS AND METHODS: One hundred twenty-six metastatic cancer patients seeing 30 oncologists at 12 outpatient clinics in New South Wales, Australia, participated in the study. Patients were diagnosed with incurable metastatic disease within 6 weeks to 6 months of recruitment. Patients completed a survey eliciting their preferences for prognostic information, including type, quantity, mode, and timing of presentation; anxiety and depression levels; and information and involvement preferences. RESULTS: More than 95% of patients wanted information about side effects, symptoms, and treatment options. The majority wanted to know longest survival time with treatment (85%), 5-year survival rates (80%), and average survival (81%). Words and numbers were preferred over pie charts or graphs. Fifty-nine percent (59%) wanted to discuss expected survival when first diagnosed with metastatic disease. Thirty-eight percent and 44% wanted to negotiate when expected survival and dying, respectively, were discussed. Patients with higher depression scores were more likely to want to know shortest time to live without treatment (P = .047) and average survival (P = .049). Lower depression levels were significantly associated with never wanting to discuss expected survival (P = .03). Patients with an expected survival of years were more likely to want to discuss life expectancy when first diagnosed with metastases (P = .02). CONCLUSION: Most metastatic cancer patients want detailed prognostic information but prefer to negotiate the extent, format, and timing of the information they receive from their oncologists.<br /

Adjuvant chemotherapy with or without bevacizumab in patients with resected non-small-cell lung cancer (E1505): an open-label, multicentre, randomised, phase 3 trial.

BackgroundAdjuvant chemotherapy for resected early-stage non-small-cell lung cancer (NSCLC) provides a modest survival benefit. Bevacizumab, a monoclonal antibody directed against VEGF, improves outcomes when added to platinum-based chemotherapy in advanced-stage non-squamous NSCLC. We aimed to evaluate the addition of bevacizumab to adjuvant chemotherapy in early-stage resected NSCLC.MethodsWe did an open-label, randomised, phase 3 trial of adult patients (aged ≥18 years) with an Eastern Cooperative Oncology Group performance status of 0 or 1 and who had completely resected stage IB (≥4 cm) to IIIA (defined by the American Joint Committee on Cancer 6th edition) NSCLC. We enrolled patients from across the US National Clinical Trials Network, including patients from the Eastern Cooperative Oncology Group-American College of Radiology Imaging Network (ECOG-ACRIN) affiliates in Europe and from the Canadian Cancer Trials Group, within 6-12 weeks of surgery. The chemotherapy regimen for each patient was selected before randomisation and administered intravenously; it consisted of four 21-day cycles of cisplatin (75 mg/m2 on day 1 in all regimens) in combination with investigator's choice of vinorelbine (30 mg/m2 on days 1 and 8), docetaxel (75 mg/m2 on day 1), gemcitabine (1200 mg/m2 on days 1 and 8), or pemetrexed (500 mg/m2 on day 1). Patients in the bevacizumab group received bevacizumab 15 mg/kg intravenously every 21 days starting with cycle 1 of chemotherapy and continuing for 1 year. We randomly allocated patients (1:1) to group A (chemotherapy alone) or group B (chemotherapy plus bevacizumab), centrally, using permuted blocks sizes and stratified by chemotherapy regimen, stage of disease, histology, and sex. No one was masked to treatment assignment, except the Data Safety and Monitoring Committee. The primary endpoint was overall survival, analysed by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00324805.FindingsBetween June 1, 2007, and Sept 20, 2013, 1501 patients were enrolled and randomly assigned to the two treatment groups: 749 to group A (chemotherapy alone) and 752 to group B (chemotherapy plus bevacizumab). 383 (26%) of 1458 patients (with complete staging information) had stage IB, 636 (44%) had stage II, and 439 (30%) had stage IIIA disease (stage of disease data were missing for 43 patients). Squamous cell histology was reported for 422 (28%) of 1501 patients. All four cisplatin-based chemotherapy regimens were used: 377 (25%) patients received vinorelbine, 343 (23%) received docetaxel, 283 (19%) received gemcitabine, and 497 (33%) received pemetrexed. At a median follow-up of 50·3 months (IQR 32·9-68·0), the estimated median overall survival in group A has not been reached, and in group B was 85·8 months (95% CI 74·9 to not reached); hazard ratio (group B vs group A) 0·99 (95% CI 0·82-1·19; p=0·90). Grade 3-5 toxicities of note (all attributions) that were reported more frequently in group B (the bevacizumab group) than in group A (chemotherapy alone) were overall worst grade (ie, all grade 3-5 toxicities; 496 [67%] of 738 in group A vs 610 [83%] of 735 in group B), hypertension (60 [8%] vs 219 [30%]), and neutropenia (241 [33%] vs 275 [37%]). The number of deaths on treatment did not differ between the groups (15 deaths in group A vs 19 in group B). Of these deaths, three in group A and ten in group B were considered at least possibly related to treatment.InterpretationAddition of bevacizumab to adjuvant chemotherapy did not improve overall survival for patients with surgically resected early-stage NSCLC. Bevacizumab does not have a role in this setting and should not be considered as an adjuvant therapy for patients with resected early-stage NSCLC.FundingNational Cancer Institute of the National Institutes of Health

Factors associated with cognitive impairment and cognitive concerns in patients with metastatic non-small cell lung cancer

BACKGROUND: Knowledge regarding cognitive problems in metastatic non-small cell lung cancer (mNSCLC) is limited. Such problems may include both patient-reported cognitive concerns and demonstrable cognitive impairment. Greater understanding of these outcomes is needed to inform rehabilitation strategies for these difficulties. We aimed to identify the frequency of cognitive problems and associated factors in patients with mNSCLC. METHODS: In this cross-sectional study, adults with mNSCLC completed validated neuropsychological tests and self-report questionnaires measuring cognitive concerns, neurobehavioral concerns, depression, demoralization, illness intrusiveness, self-esteem, and physical symptoms. Cognitive impairment (performance based) was defined according to International Cancer and Cognition Task Force criteria. Clinically significant cognitive concerns were defined by a score ≥1.5 SD below the normative mean on the Functional Assessment of Cancer Therapy-Cognitive Function Perceived Cognitive Impairment (FACT-Cog PCI). Univariate and multivariate logistic regression analyses were performed to identify associated factors. RESULTS: Of 238 patients approached, 77 participated (median age: 62 years; range: 37-82). Brain metastases were present in 41 patients (53%), and 23 (29%) received cranial irradiation. Cognitive impairment and cognitive concerns were present in 31 (40%) and 20 patients (26%), respectively. Cognitive impairment and cognitive concerns co-occurred in 10 patients (13%), but their severity was unrelated. Cognitive impairment was associated with cranial irradiation (odds ratio [OR] = 2.89; P = .04), whereas cognitive concerns were associated with greater illness intrusiveness (OR = 1.04; P = .03) and lower self-esteem (OR = 0.86; P = .03). CONCLUSIONS: Cognitive impairment and cognitive concerns are both common in patients with mNSCLC but are not necessarily related, and their risk factors differ. The association of illness intrusiveness and self-esteem with cognitive concerns can inform therapeutic interventions in this population