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Background Recognized prognostic factors associated with increased risk of recurrence in patients (pts) with HR+, HER2- early breast cancer (EBC) are higher histologic grade, larger primary tumor size, and greater lymph node involvement. Genomic assays like Oncotype DX obtain prognostic information to indicate benefit of adjuvant therapy. The objective was to examine use of genomic assays and describe demographic, clinical, and pathological characteristics of pts tested. Methods Real-world data was drawn from the Adelphi EBC I Disease Specific Programme, a cross-sectional observational study in France, Germany, Italy, Spain, United Kingdom (UK), United States (US) and Japan. 765 consulting physicians were surveyed, including questions on use of genomic assays to assess risk of recurrence. In each country, 20-64 of the physicians also completed patient record forms from Mar-Sep 2019 for up to 8 eligible pts with HR+, HER2- EBC. Results Physicians in US (n=176), UK (n=52) and Spain (n=100) reported highest use of genomic assays to categorize patients from low to intermediate risk (US 61%; Spain 57%; UK 65%) and from intermediate to high risk of recurrence (US 64%; Spain 67%; UK 65%). Lowest use was in Japan (n=134), 13% and 20%, respectively. Oncotype DX was consistently reported as the most frequently used genomic assay to assess the risk of recurrence (see table). Patient record forms were completed for 2447 pts (98% female, mean age 59.6 years, SD 13.0). Frequency of Oncotype DX testing varied by stage, with less testing in stage III pts (stage I 26% (194/755); stage II 20% (221/1130); stage III 11% (56/505) p5 cm 11% (11/105); p=0.0503). Similar patterns were seen across countries except Italy, but generally not significant. Oncotype Dx testing was less frequent in pts >50 years (age ≤50 25% (161/657); age >50 18% (318/1790); p=0.0003). Similar patterns were seen across countries, and significant in Germany (p=0.0029) and Italy (p Conclusion Use of genomic assays to assess pt risk of recurrence varied across countries. The most commonly used assay was Oncotype DX. Oncotype DX testing was less frequent amongst stage III, grade 3, large, node +ve tumors or age >50, although there were some important country variations. These data contribute to the understanding of drivers in adopting multi-gene assays within clinical practice. Genomic AssayTotal(n=729)*US (n=171)Japan (n=122)France (n=93)Germany (n=97)Italy (n=96)Spain (n=100)UK (n=50)Oncotype DX67%91%45%54%64%60%63%94%Adjuvant! Online30%23%25%29%29%34%43%42%Mammaprint29%37%30%17%24%21%52%0%Breast Cancer Index17%29%25%13%14%17%2%4%EndoPredict13%8%20%20%12%11%8%18%Prosigna11%8%11%22%4%6%21%8%*729/765 physicians who assessed all or some of their patients with EBC for risk of recurrence Citation Format: Jacqueline Brown, Rhys Williams, Alex Rider, Rosie Wild, Michael Method. Multi-country study of the use of genomic assays in HR+, HER2- early breast cancer and characteristics of patients tested [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS4-34.

Background: Breast cancer in the United States is diagnosed in over 90% of cases prior to evidence of distant metastasis (stages I–III) with approximately 70% of these cases classified as hormone receptor positive human epidermal growth factor receptor 2 negative (HR+HER2-).1 Despite primary surgery, radiation, and adjuvant endocrine/chemotherapy treatment options, approximately 20-30% of patients will experience relapse with distant metastases.2 Some clinical and pathological characteristics are known to be prognostic factors, but there are no standard definitions associated with level of risk. The objective of this study was to determine the extent of mortality associated with clinical and pathological characteristics of early breast cancer (EBC) using real-world data. Methods: Eligible patients from 2010–2016 Surveillance, Epidemiology, and End Results (SEER) data were aged ≥18 years and had a diagnosis of stage I, II, or III breast cancer with no distant metastases. Patients with HR-HER2- breast cancer were excluded. Mortality rates (95% confidence interval) by HER2 status and, for HR+HER2- tumors, by cancer stage, Bloom-Richardson (BR) grade, ipsilateral auxiliary lymph nodes status, and tumor size were estimated using Kaplan-Meier methods. Results: A total of 257,278 breast cancer patients were included: 214,578 HR+HER2-, 30,122 HR+HER2+, and 12,578 HR-HER2+. Mean age was 61.5 years, 99.1% were female, and 70.1% were white/non-Hispanic. The 5-year mortality rates were similar for HR+HER2- (12.3%) and HR+HER2+ (12.2%), whereas HR-HER2+ was numerically higher (16.8%). Within the HR+HER2- group, the 5-year mortality rates for subgroups are shown in Table 1. The highest mortality rate for both the node positive and micrometastases subgroups was approximately 30% for those who had 1–3 ipsilateral auxiliary lymph nodes, BR grade 3, and tumor size ≥5 cm. Conclusions: Patients with HR+HER2- EBC had similar mortality rates to patients with HR+HER2+ EBC. In patients with HR+HER2- EBC, higher mortality rates were numerically associated with ≥4 positive lymph nodes, BR grade 3, and greater tumor size. The effect on mortality was compounded with combinations of these histopathologic characteristics. References: 1. Howlander N, et al. J Natl Cancer Inst 2014;106:dju055; 2. Cardoso F, et al. Breast 2018;39:131-8. Table 1. Kaplan-Meier 5-year mortality estimates for patients with HR+HER2- early breast cancer by stage, grade, nodal status, and tumor size Node positiveN1mi: micrometastasesNode negativen=50,321n=10,096n=154,161 Mortality rate, % (95% CI)Mortality rate, % (95% CI)Mortality rate, % (95% CI)Overall18.15 (17.70–18.60)10.31 (9.51–11.11)10.54 (10.33–10.74)Stage INA7.29 (6.39–8.20)8.35 (8.13–8.56)Stage II12.56 (12.06–13.06)13.39 (11.91–14.87)16.69 (16.17–17.21)Stage III26.41 (25.61–27.22)19.10 (15.13–23.07)44.46 (40.69–48.23)1–3 Ips Ax nodes positive12.93 (12.43–13.43)9.96 (9.14–10.78)NA≥4 Ips Ax nodes positive24.75 (23.82–25.69)22.23 (15.64–28.82)NABR grade 325.62 (24.63–26.61)15.25 (13.09–17.41)14.24 (13.60–14.89)Tumor size Citation Format: Jacqueline Brown, Michael W Method, David R Nelson. Mortality rates associated with clinical and pathological characteristics of hormone receptor positive human epidermal growth factor receptor 2 negative early breast cancer: An analysis of the 2010-2016 surveillance, epidemiology, and end results data [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-08-18.

Background: Globally, malaria is one of the six major causes of deaths from communicable diseases. In South Africa, malaria is known to be endemic in three provinces. Two large trials, AQUAMAT and SEAQUAMAT, demonstrated the superiority of intravenous (IV) artesunate compared to quinine. A systematic review (including the above trials) demonstrated a mortality benefit for adult patients treated with artesunate, but included studies that were conducted in Asia with no adult data available for Africa. Given the lack of local data, we conducted this study to investigate the use of artesunate for the treatment of severe malaria at two academic adult intensive care units (ICUs) in Johannesburg. Methods: We undertook a retrospective patient record review. All patients admitted to the two ICUs and treated for severe malaria using artesunate were included. The study period extended from April 2010 to April 2014. The primary outcome was to determine the observed mortality and relate it to the predicted mortality based on the Acute Physiology and Chronic Health Evaluation (APACHE II) severity of illness score. The ratio of the observed mortality to the expected mortality based on the APACHE II severity of illness score provides a standardised mortality ratio (SMR). Clinical and laboratory parameters data were analysed. Results: There were 56 patients included in the study, of which 40 were male (71.4%). The mean APACHE II score was 19 (standard deviation 5.4). We observed a lower than predicted mortality rate of 21.4% (SMR 0.66). Human immunodeficiency virus (HIV) was the most prevalent comorbidity (32%). There was no travel history in 26.8% of patients. Heart rate, respiratory rate and Glasgow Coma Scale (GCS) all improved significantly from admission to the time of discharge ( p ≤ 0.01). Acidaemia, bilirubin, urea and bleeding risk (platelet count) also improved ( p ≤ 0.01). Mechanical ventilation was associated with an increased risk of death (OR 35; CI 7.0–182). Conclusion: In this retrospective two-centre study, IV artesunate was associated with a lower than predicted mortality in adult patients with severe malaria requiring ICU admission.

Necitumumab (Neci) was the first biologic approved by the FDA for use in combination with gemcitabine and cisplatin (Neci + GCis) in first-line treatment of metastatic squamous non-small cell lung cancer (msqNSCLC). The potential financial impact on a health plan of adding Neci + GCis to drug formularies may be important to value-based decision makers in the United States, given ever-tightening budget constraints.To estimate the budget impact of introducing Neci + GCis for first-line treatment of msqNSCLC from U.S. commercial and Medicare payer perspectives.The budget impact model estimates the costs of msqNSCLC before and after adoption of Neci + GCis in hypothetical U.S. commercial and Medicare health plans over a 3-year time horizon. The eligible patient population was estimated from U.S. epidemiology statistics. Clinical data were obtained from randomized clinical trials, U.S. prescribing information, and clinical guidelines. Market share projections were based on market research data. Cost data were obtained from online sources and published literature. The incremental aggregate annual health plan, per-patient-per-year (PPPY), and per-member-per-month (PMPM) costs were estimated in 2015 U.S. dollars. One-way sensitivity analyses were conducted to assess the effect of model parameters on results.In a hypothetical 1,000,000-member commercial health plan with an estimated population of 30 msqNSCLC patients receiving first-line chemotherapy, the introduction of Neci + GCis at an initial market share of approximately 5% had an overall year 1 incremental budget impact of $88,394 ($3,177 PPPY, $0.007 PMPM), representing a 2.9% cost increase and reaching $304,079 ($10,397 PPPY, $0.025 PMPM) or a 7.4% cost increase at a market share of 14.7% in year 3. This increase in total costs was largely attributable to Neci drug costs and, in part, due to longer survival and treatment duration for patients treated with Neci+GCis. Overall, treatment costs increased by $81,812 (13.5%), and disease costs increased by $7,951 (0.4%), whereas adverse event costs decreased by $1,368 (0.5%) in year 1. From the Medicare perspective, the overall year 1 incremental budget impact was $438,056 ($0.037 PMPM, $3,112 PPPY), representing a 3.0% cost increase. The higher incremental budget in Medicare, compared with commercial plans, was due to higher msqNSCLC incidence in the older Medicare patients (154 vs. 30 patients, respectively). Results were most sensitive to Neci drug costs.Based on projected market shares, coverage for first-line therapy with Neci + GCis appeared to modestly affect overall U.S. health care budgets for msqNSCLC-related care. Given the small eligible patient population, the PMPM budgetary impact on a commercial health plan of reimbursing Neci + GCis in the first year was less than $0.01, rising with increased use of Neci + GCis to $0.025 in the third year. The real-world effect of Neci + GCis needs to be evaluated to validate this analysis; however, these findings may help policymakers in making coverage decisions for Neci + GCis.This study was funded by Eli Lilly and Company. Molife, Brown, Tawney, and Cuyun Carter are equity holders and employees of Eli Lilly and Company. Bly, Cinfio, and Klein are employees of Medical Decision Modeling, which received funding from Eli Lilly and Company to conduct this research and prepare this manuscript.

The risk of venous thromboembolism (VTE) is increased in individuals with cancer, particularly in those with multiple myeloma. The immunomodulatory agents (IMiDs) thalidomide, lenalidomide and pomalidomide are commonly used to treat multiple myeloma and other hematologic malignancies and are associated with increased risk of VTE. Current National Comprehensive Cancer Network (NCCN) guidelines (v.1.2016) on cancer-associated VTE utilize a risk assessment model based on a few small studies to guide VTE prophylaxis for multiple myeloma patients being treated with an IMiD (Palumbo, et al. Leukemia, 2008). Aspirin is recommended for lower risk patients while prophylactic-dose low molecular weight heparin or therapeutic warfarin are recommended for higher risk patients. The use of direct oral anticoagulants (DOACs) for cancer-associated VTE is currently under investigation (Raskob, et al. Lancet Haematol, 2016). Little is known about their role in VTE prophylaxis in patients on IMiDs. The purpose of this study was to explore the use of DOACs in patients receiving IMiDs. We performed a retrospective chart review of all patients at the University of Virginia Health System who received an IMiD and who were taking either a DOAC or warfarin between January 1, 2010 and December 31, 2015. DOACs included dabigatran, rivaroxaban, and apixaban. IMiDs included lenalidomide, thalidomide, and pomalidomide. The primary endpoint was to assess the safety of DOACs as compared to warfarin, and the secondary endpoint was to assess their efficacy. We collected baseline patient information, as well as diagnosis, IMiD, anticoagulant, antiplatelet agent and dose, duration of treatment, concurrent antineoplastic therapies, and thrombotic risk factors. We utilized the NCCN definitions of individual and myeloma-related thrombotic risk factors. Many patients had changes in their IMiD or anticoagulation. Thus, separate encounters were collected, where an encounter was the combination of an IMiD agent and dose, the anticoagulant, the antiplatelet agent (if any), and the thrombotic risk profile for that time period. Descriptive analyses were performed on all encounters in both groups. Rates of bleeding and thrombotic events were calculated. There were 21 discrete patients in the DOAC group and 16 in the warfarin group. Characteristics and outcomes are described in Table 1. There were four non-major bleeding events in the DOAC group; two of the four bleeding events occurred while on concomitant aspirin therapy. The patient with hematuria stopped anticoagulation and cystoscopy revealed bladder cancer. The other patients did not change or stop therapy. There were six bleeding events in the warfarin group: two were major and four were non-major. The two major events were gastrointestinal bleeding (GIB) and a subarachnoid hemorrhage (SAH). Neither event occurred while on concomitant antiplatelet therapy. The GIB required cessation of therapy, hospitalization, and transfusions. The INR at the time is unknown. The SAH was preceded by a fall while INR was in therapeutic range. Both major and two of the non-major bleeding events occurred in the same patient at different time points and accounted for most of the warfarin-related bleeding events. There was one thrombotic event in the DOAC group. The patient had a non-ST segment elevation myocardial infarction (NSTEMI) while on prophylactic-dose rivaroxaban. She was not on concomitant antiplatelet therapy. Arterial thrombotic events are not typically seen with IMiDs, and the NSTEMI was thought to be related to the recent initiation of carfilzomib. There were no thrombotic events in the warfarin group. This was a retrospective, single-institution study assessing the safety and efficacy of DOACs as compared to warfarin in patients on IMiDs. In our study, all bleeding events in the DOAC group were non-major, while patients on warfarin experienced both major and non-major bleeds. Only one thrombotic event was recorded in the DOAC group. DOACs may represent an attractive alternative to warfarin for VTE prophylaxis in these patients, given no need for routine monitoring and fewer dietary restrictions. Prospective studies in this population are warranted. Disclosures No relevant conflicts of interest to declare.

Introduction: Cost-effectiveness analyses often inform healthcare reimbursement decisions. The preferred measure of effectiveness is the quality adjusted life year (QALY) gained, where the quality of life adjustment is measured in terms of utility. Areas covered: We assessed the availability and variation of utility values for health states associated with advanced or metastatic non-small cell lung cancer (NSCLC) to identify values appropriate for cost-effectiveness models assessing alternative treatments. Our systematic search of six electronic databases (January 2000 to August 2015) found the current literature to be sparse in terms of utility values associated with NSCLC, identifying 27 studies. Utility values were most frequently reported over time and by treatment type, and less frequently by disease response, stage of disease, adverse events or disease comorbidities. Expert commentary: In response to rising healthcare costs, payers increasingly consider the cost-effectiveness of novel treatments in reimbursement decisions, especially in oncology. As the number of therapies available to treat NSCLC increases, cost-effectiveness analyses will play a key role in reimbursement decisions in this area. Quantifying the relationship between health and quality of life for NSCLC patients via utility values is an important component of assessing the cost effectiveness of novel treatments.

OBJECTIVE To describe treatment patterns and resource utilisation in France, Germany, Spain and the United Kingdom (UK) in patients with unresectable locally advanced and/or metastatic gastro-oesophageal adenocarcinoma (GEA), who failed first-line fluoropyrimidine/platinum treatment. METHODS Treating physicians completed a web-based chart review (2013-2015). Eligible patients were ≥ 18 years old; had unresectable locally advanced and/or metastatic gastric adenocarcinoma including the gastro-oesophageal junction; received first-line fluoropyrimidine/platinum-based therapy; and had ≥ 3 months of follow-up after first-line discontinuation. Data were summarised descriptively for each country. RESULTS There were n = 201 patients in France, n = 202 in Germany, n = 208 in Spain and n = 200 in the UK whose charts were reviewed. Percentages of patients receiving second-line therapy were 55% (France), 48% (Germany), 54% (Spain) and 29% (UK). At the start of second-line therapy, most patients had an ECOG performance status of 1 (range 0-3). Second-line therapy was primarily monotherapy, but agents used varied within and across countries. Supportive care use and resource utilisation were frequent whether receiving additional therapy or not; >60% patients had clinic visits unrelated to chemotherapy administration, and > 30% has ≥ 1 hospital admission. CONCLUSIONS For the time of study, established GEA treatment guidelines were generally followed. However, therapies varied widely in the second-line setting.

e18581 Background: While most patients (pts) with HR+, HER2- early breast cancer (EBC) do not experience disease recurrence, those with high risk clinicopathologic features may have recurrence within the first few years on adjuvant endocrine therapy (AET). This study estimates risk of recurrence in pts with EBC based on clinicopathologic features and evaluates the medical need for more efficacious treatments using US oncology practice data. Methods: This retrospective study used the nationwide Flatiron Health electronic health record derived deidentified database. The cohort included pts with HR+, HER2- stage I-III breast cancer, diagnosed Jan 2011-Mar 2020, who received surgery and AET. Clinicopathologic features were used to identify a ‘high risk (HiR) group’ (≥ 4 positive axillary lymph nodes (LN), or 1-3 positive axillary LN and ≥ 1 of the following: Grade 3, tumor size ≥ 5 cm, or Ki-67 ≥ 20%) and ‘low risk (LoR) group’ (pts who do not meet above criteria, including a subset with node negative (N0) disease). Cox proportional hazards regression models compared invasive disease-free survival (IDFS) and distant relapse-free survival (DRFS) from AET initiation between groups according to a sequential gatekeeping strategy and stepwise analysis: first compare HiR group to N0 pts; if significant then compare HiR to LoR group. Results: 557 (13.8%) pts were in the HiR group and 3,471 (86.2%) in the LoR group (including 2,867 N0 pts). The study population (median age 64 yrs) was predominantly female (99.2%), white (69.4%) and postmenopausal (75.6%) with median follow-up of 39.6 months. Pts in the HiR group were younger and more likely premenopausal, have a BRCA mutation, invasive lobular carcinoma and less likely to have received an Oncotype DX test compared to LoR pts. Of the 557 HiR pts, 231 (41.5%) had ≥ 4 positive LN and 326 (58.5%) had 1-3 positive axillary LN with additional risk factor(s): tumor size ≥ 5 cm (11.7%), histologic grade 3 (32.0%), and/or Ki-67 ≥ 20% (31.6%). Most HiR pts received radiotherapy (82.4%) and chemotherapy (68.1%). Significant differences in IDFS and DRFS were observed between HiR group and N0 and LoR groups (logrank test p < .0001 for all). The 2-year IDFS rate was 88.1% in the HiR group, compared to 97.4% in N0 pts and 97.1% in the LoR group; 2-year DRFS rates were 89.0% compared to 97.9% and 97.7%, respectively. Pts in the HiR group had significantly higher hazard of invasive disease recurrence or death compared to N0 (HR = 3.42, 95% CI: 2.69-4.34, p < .0001) and LoR group (HR = 3.07, 95% CI: 2.46-3.84, p < .0001). Similar results observed for DRFS (HiR vs N0: HR = 3.46, 95% CI: 2.70-4.44, p < .0001; HiR vs LoR HR = 3.16, 95% CI: 2.50-3.98, p < .0001). Conclusions: Approximately 12% of pts with EBC and high risk clinicopathologic features experienced invasive disease recurrence or death within 2 years of initiating AET. Optimal use of standard therapies and novel treatment options are needed to prevent early recurrence and metastases in these pts.

Direct oral anticoagulants have been shown safe and effective in the treatment of pulmonary emboli and deep vein thrombi. Their role in the treatment of patients with hypercoagulability is uncertain. We designed a retrospective exploratory analysis of all patients with definite heparin induced thrombocytopenia (HIT) and antiphospholipid syndrome (APS) that were treated with either apixaban or rivaroxaban from September 2011 through November 2015. Patients were reviewed for several clinico-pathologic features, including efficacy and safety. 23 patients were identified (12 patients with HIT and 11 patients with APS). Sixteen patients (70 %) were treated with apixaban and seven patients (30 %) were treated with rivaroxaban over a median follow up of 7 months (range 2-39). Zero patients developed recurrent thrombi. Two patients being treated for HIT developed major bleeding leading to discontinuation of all anticoagulation. Therefore, apixaban and rivaroxaban appear safe and effective for treatment of patients with HIT and APS in this small retrospective cohort and should be considered on an individual basis for patients who refuse, fail or are intolerant of warfarin. There were no sources of funding.

Background: The objectives of this systematic review and meta-analysis were to compare the survival, toxicity, and quality of life of patients treated with necitumumab in combination with gemcitabine and cisplatin. These agents were investigated in published randomized controlled trials (RCTs) of patients with squamous non-small cell lung cancer (NSCLC) in the first-line setting. Methods: The systematic review was executed on January 27, 2015, and updated on August 21, 2016, using a pre-specified search strategy. Searches were conducted using PubMed, Medline, and EMBASE, with supplemental searches using the Evidence Based Medicine Reviews and ClinicalTrials.gov to identify RCTs published in English from 1995–2016 and reporting at least one of the primary outcomes [overall survival (OS), progression-free survival (PFS), toxicity, or quality of life] in patients who received first-line treatment for advanced or metastatic squamous NSCLC. Study quality and risk of bias were assessed using the Physiotherapy Evidence Database (PEDro) scale and Cochrane risk of bias tool, respectively. A Baysian network meta-analysis was performed on the primary outcomes. Hazard ratios (HRs) were evaluated for the primary analysis; secondary analyses were conducted using median OS data. Planned sensitivity analyses were conducted including reanalysis using a Frequentist approach and limiting analyses to subsets based on clinical and demographic covariates. Results: The systematic literature review resulted in identification of 4,016 unique publications; 40 publications (35 unique trials) were eligible for inclusion. Eight studies connected to a common network for the OS analysis using HR data. The majority of studies were not limited to squamous NSCLC, thus analyzable data were limited to a subset of data within the published trials. Carboplatin + S-1 and necitumumab in combination with gemcitabine and cisplatin were associated with lower HRs for OS versus all other comparators. Nine studies connected to the network for the PFS analysis in which necitumumab in combination with gemcitabine and cisplatin was associated with the lowest HR. Data were not available to analyze toxicity or quality of life. Conclusions: Although the results suggest that carboplatin + S-1 and necitumumab in combination with gemcitabine and cisplatin may have value in terms of OS versus other comparators, the results should be interpreted with caution due to the limited number of studies (with few focused exclusively on squamous NSCLC) and wide credible intervals.

Cancer patients treated with epidermal growth factor receptor inhibitors (EGFRIs) frequently experience skin toxicities (rash) that can compromise their quality of life and lead to dose reduction or discontinuation of treatment. Reflecting the need for effective management of EGFRI-associated rash, a number of clinical practice guidelines and management recommendations have been developed. The objective of this systematic review is to identify and summarize all available published recommendations of rash management strategies and evaluate their basis of evidence, to describe consensus in the recommendations, and where there is a lack of consensus to describe the opportunities for future clinical research to improve clinical practice in the management of EGFRI rash. Fifty-nine articles published from 2005-2011 were selected for inclusion in the systematic review. Common drug recommendations were oral and topical antibiotics, topical corticosteroids, and antihistamines; low-grade rash was generally recommended to be managed with topical antibiotics or corticosteroids, grade 2 rash with oral antibiotics or antihistamines, and severe grades of rash with oral corticosteroids or delay/dose reduction of EGFRI. The focus of clinical practice guidelines and recommendations was on reactive management. A better understanding of pre-emptive versus reactive treatment with the implementation of appropriately designed randomized controlled studies could support a more effective management of EGFRI-associated rash and improve patient outcomes. Consideration of patients' self-reported outcomes and consistent grading of rash toxicity are also recommended. Funding/sponsor: Eli Lilly & Co, Bristol-Myers Squibb.

Background: In the SQUIRE study, adding the anti-epidermal growth factor receptor (EGFR) IgG1 antibody necitumumab to first-line gemcitabine and cisplatin (GC + N) in advanced squamous non-small-cell lung cancer (sqNSCLC) significantly improved overall survival (OS); the safety profile was acceptable. We explored data for the German subpopulation (N = 96) of SQUIRE patients with EGFR-expressing tumors. Patient and Methods: Patients with stage IV sqNSCLC were randomized 1:1 to up to 6 cycles of open-label GC + N or GC alone. GC + N patients with no progression continued on necitumumab monotherapy until disease progression or intolerable toxicity. The primary endpoint was OS; the secondary endpoints included progression-free survival (PFS), safety and health-related quality of life (EQ-5D, Lung Cancer Symptom Scale (LCSS)). Results: The 96 German SQUIRE patients with EGFR-expressing tumors (GC + N 42, GC 54) received a median of 4 GC cycles; the GC + N patients received 5 cycles of necitumumab. Adding necitumumab was associated with 41% risk reduction of death (hazard ratio (HR) 0.59, 95% confidence interval (CI) 0.37-0.94, p = 0.026) and 44% risk reduction of progression (HR 0.56, 95% CI 0.33-0.95, p = 0.029). Adverse events typically associated with EGFR antibody treatment (including rash, hypomagnesemia) were more common with GC + N. The time to deterioration of the EQ-5D and LCSS scores showed no notable differences between the treatment arms, except for appetite loss (delayed for GC + N). Conclusion: The survival benefit from adding necitumumab to first-line GC was more pronounced in the German SQUIRE subpopulation with EGFR-expressing tumors than in the overall (intention-to-treat) population; toxicity was manageable and consistent with the overall population.

It is estimated that up to 20%–25% of patients with colonic diverticula will progress to diverticulitis.1,2 The diagnosis of acute diverticulitis is typically made using a combination of history, clinical exam, biochemical investigations and diagnostic imaging. Computed tomography (CT) has emerged as the imaging modality of choice given its high sensitivity and specificity for the diagnosis of diverticulitis, with some studies reporting up to 100% in either measure.3–8 Computed tomography findings of diverticula, inflammation of pericolic fat, bowel wall thickness greater than 4 mm and/or pericolic fluid/abscess are highly suggestive of acute diverticulitis.1,8,9 A CT scan also provides prognostic information and guides management by determining whether the diverticulitis is complicated by abscess, fistula formation, stricture/obstruction or free rupture. While most cases of uncomplicated diverticulitis respond well to conservative treatment, complicated diverticulitis requires surgical intervention. There is overlap in the findings of acute diverticulitis and colorectal cancer (CRC), and CT findings alone are insufficient to exclude malignancy approximately 10% of the time.1,10 As a result, the American Society of Colon and Rectal Surgeons recommend performing a colonoscopy to exclude a potential malignancy after an episode of acute diverticulitis has resolved.1,9,11 However, since the advent of multidetector CT scanners that are capable of capturing images more quickly and thus reduce motion artifacts, the image qualities and diagnostic accuracy of CT scans have improved substantially. With increased resolution of the newer 64-slice CT scans that are currently in widespread use, acute diverticulitis can be diagnosed more accurately,12,13 and it may be possible to adequately distinguish acute diverticulitis from malignancy based on radiological features alone. Routine follow-up colonoscopy may no longer be required in patients with acute diverticulitis. The primary aim of this study was to determine the prevalence of colon cancer in patients with diverticulitis diagnosed on high-resolution CT scan to determine the need for follow-up colonoscopy in this patient population.

Collaboration between nations and sectors is crucial to improve regional preparedness against pandemic influenza. In 2008, a Virtual Symposium was organized in the Asia-Pacific region by the Asia-Pacific Economic Cooperation Emerging Infections Network (APEC EINet) to discuss pandemic preparedness. The multipoint videoconference lasted approximately 4.5 hours and was attended by 16 APEC members who shared best practices in public-private partnerships for pandemic influenza preparedness planning. Twelve of the 16 APEC members who participated responded to a post-event survey. The overall experience of the event was rated highly. Partnering public health, technology and business communities to discuss best practices in preparedness using videoconferencing may be an effective way to improve regional preparedness. Utilization of videoconferencing on a routine basis should be considered to improve preparedness among APEC members and enhance its usability during a pandemic.

Introduction Necitumumab, a second-generation, recombinant human immunoglobulin G1 epidermal growth factor receptor antibody in the phase 3 SQUIRE trial (NCT00981058), increased survival benefit for patients randomized to receive necitumumab plus gemcitabine-cisplatin compared with those who received gemcitabine-cisplatin. Here we characterize health-related quality of life (HRQoL) and tolerability results. Methods A total of 1093 patients with stage IV squamous non–small cell lung cancer were randomized 1:1 to receive necitumumab (800 mg absolute dose intravenously [IV]) plus gemcitabine-cisplatin (gemcitabine = 1250 mg/m 2 IV on days 1 and 8; cisplatin = 75 mg/m 2 IV on day 1) or gemcitabine-cisplatin alone (every 21 days) for up to six cycles. Patients receiving necitumumab plus gemcitabine-cisplatin without disease progression continued necitumumab until progression. HRQoL was measured by Eastern Cooperative Oncology Group performance status, the Lung Cancer Symptom Scale (LCSS), and the European Quality of Life Five-Dimensions questionnaire. Efficacy and LCSS outcomes were analyzed using the baseline maximum severity score of the LCSS. Tolerability was measured in terms of exposure to the study treatment and adverse events. Hospitalization rates were collected. Results Most patients in both study arms similarly maintained Eastern Cooperative Oncology Group performance status and comparable LCSS and European Quality of Life Five-Dimensions questionnaire assessments. Patients with a higher baseline LCSS had a greater survival benefit on the necitumumab arm. Chemotherapy exposure was similar in both treatment arms; 51% of patients on the necitumumab plus gemcitabine-cisplatin arm continued on single-agent necitumumab. The most frequent grade 4 adverse events were neutropenia (6.1% versus 7.9%) and thrombocytopenia (3.2% versus 4.3%) in the necitumumab plus gemcitabine-cisplatin versus gemcitabine-cisplatin arms, respectively. Hospitalizations were slightly higher with necitumumab plus gemcitabine-cisplatin (36.4%) than with gemcitabine-cisplatin (34.0%). Conclusions The addition of necitumumab to gemcitabine-cisplatin was well tolerated, did not negatively affect HRQoL or toxicity, and particularly benefited patients with more severe baseline symptoms or lower HRQoL.

In a lung cancer survey in 2000 we showed significantly less favourable stage distribution and lower resection rate in Teesside (UK) than in the comparable industrialised area of Varese (Italy). Lung cancer services in Teesside were subsequently reorganised according to National Cancer Plan recommendations.For all new lung cancer cases diagnosed in Teesside (n=324) and Varese (n=260) during the 12 months October 2010 to September 2011 (hereafter 'the 2010 cohort'), demographic, clinico-pathological and disease management data were prospectively recorded using the same database and protocol as the 2000 survey. Findings were analysed focusing on resection rate.In the 2010 cohort compared with 2000, both in Teesside and Varese emergency referral decreased (p0.001), performance status improved (p0.001), but cancer stage shift was not seen; resection rate improved in Teesside, from 7% to 11% (p=0.054), and was unchanged in Varese (24%). Moreover, in Teesside compared with Varese the stage distribution remained less favourable, stage I-II non-small cell lung cancer (NSCLC) proportion being respectively 12% and 19% (p=0.040), and resection rate in all lung cancers remained lower (11% and 24%; p0.001). On multivariate analysis, resection predictors in Teesside were as follows: stage I-II NSCLC (OR 86.14; 95% CI 31.80 to 233.37), performance status 0-1 (OR 5.02; 95% CI 1.48 to 17.07), belonging to 2010 cohort (OR 2.85; 95% CI 1.06 to 7.64).In Teesside the main independent predictor of resection was disease stage; in 2010-2011 compared with 2000, lung cancer service improved but stage shift did not occur, and resection rate increased but remained significantly lower than in Varese.

Objectives: Congenital heart defects (CHD) are an important cause of death and morbidity in early childhood, but the effectiveness of alternative newborn screening strategies in preventing the collapse or death—before diagnosis—of infants with treatable but life-threatening defects is uncertain. We assessed their effectiveness and efficiency to inform policy and research priorities.Methods: We compared the effectiveness of clinical examination alone and clinical examination with either pulse oximetry or screening echocardiography in making a timely diagnosis of life-threatening CHD or in diagnosing clinically significant CHD. We contrasted their cost-effectiveness, using a decision-analytic model based on 100,000 live births, and assessed future research priorities using value of information analysis.Results: Clinical examination alone, pulse oximetry, and screening echocardiography achieved 34.0, 70.6, and 71.3 timely diagnoses per 100,000 live births, respectively. This finding represents an additional cost per additional timely diagnosis of £4,894 and £4,496,666 for pulse oximetry and for screening echocardiography. The equivalent costs for clinically significant CHD are £1,489 and £36,013, respectively. Key determinants of cost-effectiveness are detection rates and screening test costs. The false-positive rate is very high with screening echocardiography (5.4 percent), but lower with pulse oximetry (1.3 percent) or clinical examination alone (.5 percent).Conclusions: Adding pulse oximetry to clinical examination is likely to be a cost-effective newborn screening strategy for CHD, but further research is required before this policy can be recommended. Screening echocardiography is unlikely to be cost-effective, unless the detection of all clinically significant CHD is considered beneficial and a 5 percent false-positive rate acceptable.

Antipsychotic discontinuation rates are a powerful indicator of medication effectiveness in schizophrenia. We examined antipsychotic discontinuation in the Schizophrenia Outpatient Health Outcomes (SOHO) study, a 3-year prospective, observational study in outpatients with schizophrenia in 10 European countries. Patients (n=7728) who started antipsychotic monotherapy were analyzed. Medication discontinuation for any cause ranged from 34% and 36% for clozapine and olanzapine, respectively, to 66% for quetiapine. Compared to olanzapine, the risk of treatment discontinuation before 36 months was significantly higher for quetiapine, risperidone, amisulpride, and typical antipsychotics (oral and depot), but similar for clozapine. Longer medication maintenance was associated with being socially active and having a longer time since first treatment contact for schizophrenia, whereas higher symptom severity, treatment with mood stabilizers, substance abuse, having hostile behaviour were associated with lower medication maintenance. Antipsychotic maintenance in SOHO was higher than the results of previous randomized studies.

Aims. This paper presents a comprehensive systematic review of literature carried out to identify studies of interventions to improve uptake, adherence and professional compliance in cardiac rehabilitation. Background. Guidelines recommend that cardiac rehabilitation should be offered to patients following acute myocardial infarction and revascularization. Uptake and adherence are low, particularly in women, older people, and socially deprived and ethnic minority patients. Although patient, service and professional barriers to rehabilitation uptake have been described, no attempt has been made to evaluate systematically interventions aimed at improving uptake and adherence in cardiac rehabilitation. Methods. A comprehensive search strategy identified studies of cardiac rehabilitation, using the terms uptake, adherence and compliance. The search included grey literature, hand searching of specialist journals and conference abstracts. No language restriction was applied. Studies were summarized in three qualitative overviews and assessed by quality of evidence. Results. From 3261 publications identified, 957 were acquired on the basis of title or abstract. Few studies were of sufficient quality to make specific recommendations. Six, 12 and five studies, respectively, provided adequate information on methods to improve uptake, adherence or professional compliance. A minority of studies were randomized controlled trials. Studies of motivational and self-management strategies and use of lay volunteers showed some promise in improving rehabilitation uptake or lifestyle change. Nurse-led coordination of care after hospital discharge may have a role in improving rehabilitation uptake. Limited information was provided on resource implications, and there was a lack of studies with under-represented groups. The literature contained numerous suggested interventions which merit evaluation in appropriately designed studies. Conclusions. Little research has been reported evaluating interventions to improve uptake, adherence and professional compliance in cardiac rehabilitation. A wide range of possible interventions was identified and further evaluations of methods are indicated.

Background: The Emerging Infections Network is a mature electronic network that links Public Health professionals in the Asia Pacific through regular e-mail bulletins and an extensive Web site (http://www.apec.org/infectious). Emerging infections is a new area of study; learning materials help foster education. Our objective is to quantify the response of the network to the introduction of distance-learning materials on the Web site. Methods: Distance-learning materials, developed by the University of Washington School of Public Health, were field tested and launched on the site. Publicity was carried out prior to the launch of the materials. Access was tracked prospectively using server counts of page downloads. Results: Web access increased substantially during the month after the materials were launched, especially among Asia based computers. The effect was isolated to the distance-learning pages, and not general to the site. Conclusions: This Web site appears to be responsive to the advertisement and to the materials. Prospective Web-site monitoring proved useful.

Despite advances in the treatment of nonsquamous non-small cell lung cancer (NSCLC), therapeutic choices and overall disease course for squamous NSCLC have remained relatively unchanged over the past several years. We provide a detailed account of current treatment patterns, healthcare use, and survival in real-world clinical settings for metastatic squamous NSCLC.Patients aged ≥65 years with metastatic squamous NSCLC diagnosed 2001-2009 were identified and followed through 2010 using the Surveillance, Epidemiology and End Results-Medicare database. Treatment patterns were descriptively analyzed. Multivariate logistic regressions were estimated to identify predictors of treatment pattern events; generalized linear models were estimated for total all-cause and NSCLC-related costs to assess cost drivers.Of 17,133 patients, 72% received cancer-directed therapy (surgery, radiation, chemotherapy, or biologic therapy), whereas 28% received only supportive care. Median survival was significantly longer in patients receiving cancer-directed therapy (8 months) than in patients receiving supportive care only (2 months) (P0.0001). An agent-specific first-line chemotherapy regimen was identified for 91% of the 7700 patients who received chemotherapy. Among these, the most common first-line regimen was carboplatin-paclitaxel combination therapy (46%). Common second-line regimens were gemcitabine monotherapy (16%) and pemetrexed monotherapy (11%). Factors associated with decreased odds of receiving cancer-directed treatment were black versus white race (OR, 0.72; 95% CI, 0.64-0.82), residence in the West versus South (OR, 0.73; 95% CI, 0.66-0.81), and metastatic disease at initial diagnosis versus progression to metastatic disease (OR, 0.77; 95% CI, 0.70-0.84).Our study shows that prognosis remains poor for patients with metastatic squamous NSCLC, even among those receiving treatment, but particularly for patients limited to supportive care only, highlighting the continuing unmet medical need in this population. Additionally, our analysis indicates that selections for second-line and third-line chemotherapies are not necessarily consistent with National Comprehensive Cancer Network guidelines.

Development of a smart insole tracking system is described. Originally designed for healthcare applications, the system has found applications in both physical therapy and athletic training. The entire system is distributed between insole hardware, mobile device applications that interface with the insoles and a central Internet server for data warehousing and analysis. We describe the development of these components so far including a discussion of custom algorithm development required for the system. The athletic version has been commercialized while the more complex healthcare version is still under development.

Cytotoxic chemotherapy can cause local reactions with varying degrees of severity following extravasation.Today, intravenous cannulation and administration of cytotoxic chemotherapy are frequently performed by nurses.Therefore, measures which promote the prevention of extravasation are explored in this paper and suggestions for clinical practice are made.We examine extravasation-related literature, and compare the findings from both animal and human studies.Vesicants, irritants and flare reactions are defined, and management options for each are debated. Finally, in the light of experience and available evidence, a new, uncomplicated management protocol is proposed

In preparing for an influenza pandemic it has been recognised that routine communication modes are inadequate to support transnational responses to public health emergencies. We assessed the Access Grid, a high bandwidth, open source network, as a possible solution. Through the Asia Pacific Economic Cooperation Emerging Infections Network (APEC EINet), we connected various public health sites in the APEC region via the Access Grid. In January 2006, ten APEC members discussed their epidemiological situation and their pandemic planning status in a 210–min vidéoconférence. Few technical difficulties were experienced. Clinical and public health collaborations, surveillance, scenario exercises, vaccine and antiviral use, and business continuity planning were discussed. In a post-conference evaluation by five sites, the vidéoconférence was reported to be both effective and efficient in promoting regional information sharing on preparedness.

Castration-resistant prostate cancer (CRPC) is partially characterised by overexpression of antiapoptotic proteins, such as survivin. In this phase 2 study, patients with metastatic CRPC (n=154) were randomly assigned (1:2 ratio) to receive standard first-line docetaxel/prednisone (control arm) or the combination of LY2181308 with docetaxel/prednisone (experimental arm). The primary objective was to estimate progression-free survival (PFS) for LY2181308 plus docetaxel. Secondary efficacy measures included overall survival (OS), several predefined prostate-specific antigen (PSA)-derived end points, and Brief Pain Inventory (BPI) and Functional Assessment of Cancer Therapy-Prostate (FACT-P) scores. The median PFS of treated patients for the experimental arm (n=98) was 8.64 mo (90% confidence interval [CI], 7.39-10.45) versus 9.00 mo (90% CI, 7.00-10.09) in the control arm (n=51; p=0.755). The median OS for the experimental arm was 27.04 mo (90% CI, 19.94-33.41) compared with 29.04 mo (90% CI, 20.11-39.26; p=0.838). The PSA responses (≥ 50% PSA reduction), BPI, and FACT-P scores were similar in both arms. In the experimental arm, patients had a numerically higher incidence of grades 3-4 neutropenia, anaemia, thrombocytopenia, and sensory neuropathy. In conclusion, this study failed to detect a difference in efficacy between the two treatment groups.

STUDY OBJECTIVE--To compare the costs and effects of routine mammography screening by a single mediolateral-oblique view and two views (mediolateral-oblique plus craniocaudal) of each breast. DESIGN--A cost effectiveness analysis of a prospective non-randomised trial comparing one and two view mammography screening was carried out at St Margaret's Hospital, Epping. All women in the study had two view mammography. The mediolateral-oblique view was always the first image read by the radiologist. After reading the films for a clinic session, the same radiologist then went back and read both the mediolateral-oblique and craniocaudal views together. Each set of films was read by two radiologists. The main outcome measures were recall rates, number of cancers detected, screening and assessment costs, and cost effectiveness ratios. SUBJECTS--A total of 26,430 women who attended for breast screening using both one and two view mammography participated. A sample of 132 women attending for assessment provided data on the private costs incurred in attending for assessment. RESULTS--There was a reduction in the recall rate from 9.1% (2404 of 26,430) after one view screening to 6.7% (1760 of 26,430) after two view screening. The results also suggest that for every 10,000 women screened an additional five cancers would be detected earlier with two view screening. The additional health service screening cost associated with two view screening was estimated to be 3.63 pounds: the costs associated with one and two view screening policies were estimated to be 41.49 pounds and 32.99 pounds respectively. Private costs incurred were estimated to be 0.35 pounds per woman screened and 32.75 pounds per woman assessed. Two cost effectiveness ratios were calculated: an incremental health service cost per additional cancer detected of 4129 pounds and an incremental health service plus private cost per additional cancer detected of 2742 pounds. The sensitivity analysis suggested that the results were sensitive to relatively large changes in a number of parameters. These included screening costs, assessment costs, equipment life, and recall rates. CONCLUSIONS--Use of two view screening increased early cancer detection and also costs. The reduction in the recall rate with two views was not sufficiently large to make the cost of two view screening neutral. While these results are not completely generalisable, a framework is provided to allow other centres to estimate the cost effectiveness of two view screening in their locality.

AIM: To identify molecular markers shared across South African esophageal squamous cell carcinoma (ESCC) cell lines using cytogenetics, fluorescence in situ hybridization (FISH) and single nucleotide polymorphism (SNP) array copy number analysis. METHODS: We used conventional cytogenetics, FISH, and multicolor FISH to characterize the chromosomal rearrangements of five ESCC cell lines established in South Africa. The whole genome copy number profile was established from 250K SNP arrays, and data was analyzed with the CNAT 4.0 and GISTIC software. RESULTS: We detected common translocation breakpoints involving chromosomes 1p11-12 and 3p11.2, the latter correlated with the deletion, or interruption of the EPHA3 gene. The most significant amplifications involved the following chromosomal regions and genes: 11q13.3 (CCND1, FGF3, FGF4, FGF19, MYEOV), 8q24.21(C-MYC, FAM84B), 11q22.1-q22.3 (BIRC2, BIRC3), 5p15.2 (CTNND2), 3q11.2-q12.2 (MINA) and 18p11.32 (TYMS, YES1). The significant deletions included 1p31.2-p31.1 (CTH, GADD45α, DIRAS3), 2q22.1 (LRP1B), 3p12.1-p14.2 (FHIT), 4q22.1-q32.1 (CASP6, SMAD1), 8p23.2-q11.1 (BNIP3L) and 18q21.1-q21.2 (SMAD4, DCC). The 3p11.2 translocation breakpoint was shared across four cell lines, supporting a role for genes involved at this site, in particular, the EPHA3 gene which has previously been reported to be deleted in ESCC. CONCLUSION: The finding that a significant number of genes that were amplified (FGF3, FGF4, FGF19, CCND1 and C-MYC) or deleted (SFRP2 gene) are involved in the Wnt and fibroblast growth factor signaling pathways, suggests that these pathways may be activated in these cell lines.

Objectives: We investigated the association between continuous antipsychotic use and health-related quality of life (HRQL) 3-year change in the European Schizophrenia Outpatients Health Outcomes (EU-SOHO) study. Methods: EU-SOHO is an observational study of outcomes associated with antipsychotic treatment for schizophrenia in an outpatient setting. HRQL was assessed at study entry and at 6, 12, 18, 24, 30, and 36 months using the EuroQol-5D (EQ-5D). UK population time trade-off (TTO) tariffs were applied to the self-rated EQ-5D health states to calculate HRQL ratings (0 = death, 1 = best). An epoch analysis approach was used as a conceptual framework to analyze the longitudinal data. Follow-up was divided into epochs or periods of continuous treatment. When a patient changed antipsychotic treatment, he or she was considered to have a new observation. Multilevel models were employed to evaluate the association of HRQL with medication and other clinical and sociodemographic variables for each epoch. A total of 9340 patients were analyzed (42.1% women; mean age 40 years). Results: Mean EQ-5D scores increased over time; the largest improvement occurred in the first 6 months (mean increase of 0.19). Longer duration of illness and older age at first treatment were associated with worse baseline EQ-5D scores. Improvements in EQ-5D scores were greater for more socially active patients or those in paid employment. Few significant differences were found between antipsychotic medications. Olanzapine and clozapine were associated with higher HRQL increases. Conclusions: Continuous antipsychotic treatment is associated with important HRQL benefits at 3 years, most of which occurs during the first 6 months. Although some medications are associated with better HRQL outcomes, differences are small.

Background Relapse in schizophrenia is one of the greatest burdens of the illness. Aims To estimate the costs associated with relapse in a pan-European naturalistic setting. Method The SOHO study is a 3-year, prospective, observational study of 10,972 outpatients with schizophrenia across 10 European countries. The cost of resource use (inpatient stay, day care, psychiatrist visits and medication) for those who ever relapsed in three years was compared to those who never relapsed. One-year costs for both groups were also compared for a more stringent comparison. The analyses were adjusted for patient characteristics and took account of non-normality of the cost data by using a log-link function. UK unit costs were applied to resource use. The analysis was repeated after multiple imputation for missing data. Results Costs incurred by patients who ever relapsed (£14,055) during three years were almost double to those incurred by patients who never relapsed (£7417). 61% of the cost difference was accounted for by hospital stay. The impact of relapse was even greater in the 1-year cost comparison. Results from the additional analysis with imputed missing data remained largely consistent. Conclusions Our findings confirm the significant economic burden of relapse, and show such costs were mainly due to hospital stay. Nevertheless, the use of UK unit costs requires caution when interpreting this costing in the context of a specific country, as resource use and their associated costs will differ by country.

To determine the cost utility of treating schizophrenic patients with olanzapine compared with other antipsychotics in a naturalistic outpatient setting.The pan-European SOHO study is a 3-year, prospective, outpatient, observational study of outcomes associated with antipsychotic treatment, focusing on olanzapine, in ten European countries. For the cost-utility analysis, healthcare resource use (inpatient care, day care, outpatient psychiatric consultations and antipsychotic and concomitant medication use) and EQ-5D data were collected at baseline and at 3, 6 and 12 months. The perspective was that of the health service payer. UK healthcare unit costs (year 2004 values) were applied to the resource use data for the ten countries. UK population tariffs were applied to the EQ-5D data to determine utility values.An Epoch analysis was used to analyze the longitudinal data. Multivariate regression analyses that adjusted for baseline covariates were used to estimate the incremental cost and utility gains for patients treated with olanzapine compared with each of the other antipsychotics (risperidone, quetiapine, amisulpride, clozapine and oral or depot typical antipsychotics).A total of 10 972 patients were enrolled at baseline, of which 9107 completed the 12-month study period. Treatment with olanzapine was more effective in terms of QALYs gained than all of the other antipsychotic treatments. Treatment with olanzapine dominated quetiapine and amisulpride. The incremental cost for olanzapine compared with risperidone was pound sterling 226 per patient over 12 months and the incremental cost per QALY gained was pound 5156, with bootstrap analyses showing 100% of the replications falling below a pound sterling 30 000 per QALY gained threshold. Compared with treatment with clozapine, olanzapine was found to be marginally more effective, at an additional cost of pound sterling 13 per patient over 12 months and to have an incremental cost per QALY gained of pound sterling 775. Bootstrap analyses showed that 81% of replications fell below a pound sterling 30 000 per QALY gained threshold. Comparing olanzapine with oral and depot typical antipsychotics, the incremental cost was pound sterling 849 and pound sterling 1106 per patient over 12 months and the incremental cost per QALY gained was pound sterling 15 696 and pound sterling 23 331, respectively. Bootstrap analyses showed that 98% of the replications fell below a pound sterling 30 000 per QALY gained threshold for the comparison with oral typical antipsychotics, and 79% of replications for the comparison with depot preparations.Among SOHO patients, if a funding threshold of pound sterling 30 000 per QALY gained is assumed, this analysis suggests that olanzapine has a high probability of being the most cost-effective treatment compared with other antipsychotic treatments. However, comparison of olanzapine with clozapine and typical depot antipsychotics should be viewed with caution because clozapine is a second-line treatment and depot treatment is used for patients who do not adhere to their oral medication.

8099 Background: SQUIRE, a randomized, phase III study (N = 1093) demonstrated that the addition of necitumumab (N) to gemcitabine-cisplatin (GC) improved OS in patients with stage IV squamous NSCL...

184 Background: With no licensed therapies for previously treated advanced GC, little is known on how patients (pts) are managed after 1st-line chemotherapy (CTx) has failed. We present real-world data on characteristics, treatments, and resource utilization (RU) for such pts in the UK. Methods: Physicians who treat pts with advanced GC completed a web-based chart review detailing clinical and RU data for 3-4 de-identified pts each. Eligible pts were ≥18 years old, diagnosed Jan 2007-Mar 2012 with advanced GC, received 1st-line fluoropyrimidine+platinum, and had ≥3 months of follow-up after 1st-line discontinuation (DC). Data were summarized descriptively. Results: From Jun to Jul 2013, 58 physicians provided data for 200 pts. Pts’ mean age was 61 years; 69.5% were male. At advanced stage diagnosis, ECOG performance status (PS) was 21% 0, 72.5% 1, and 6.5% 2. The most common 1st-line regimens were capecitabine (cape)+oxaliplatin+epirubicin (epi) (34%), cape+cisplatin+epi (20.5%) and 5-FU+cisplatin+epi (13%). The most common reasons for 1st-line DC were completion of planned regimen (63%) and disease progression (24%). ECOG PS at 1st-line DC was 5% 0, 57.5% 1, 32% 2, 5.5% 3. 28.5% received 2nd-line, and 79% of these had PS 0/1 at start of 2nd-line. 21 unique 2nd-line regimens were reported; most common were docetaxel (28%), paclitaxel (11%), trastuzumab (9%), cape (7%) and irinotecan (7%). Among pts who received 2nd-line, 5% received 3rd-line. (See table.) The most common contributing reasons for hospitalization were palliative care and disease progression. Conclusions: In our study sample of advanced GC, the minority of pts received subsequent CTx after 1st-line CTx. There was considerable variation in 2nd-line regimens, although primarily monotherapy. Pts who received 2nd-line CTx had numerically similar or lower rates of supportive care. [Table: see text]

Aim: Characterize QoL, tolerability, and supportive care of patients (pts) receiving necitumumab (N) + gemcitabine-cisplatin (GC) in the SQUIRE study. Methods: Pts with ECOG performance status (PS) 0-2, stage IV squamous NSCLC were randomized 1:1 to GC (G = 1250 mg/m2 IV days 1, 8; C = 75 mg/m2 IV day 1) + N (800 mg absolute dose IV), or GC alone (every 21 days up to 6 cycles). Pts treated with GC + N with no disease progression (PD) continued on N monotherapy until PD. Pt reported symptoms were measured by the Lung Cancer Symptom Scale (LCSS) prior to the start of each cycle (1-6) and every 6 weeks thereafter until PD. Physician reported PS was measured before every cycle. Tolerability was measured by number of cycles received, treatment discontinuation for adverse events (AEs), rates of serious AEs (SAEs), % of pts receiving N monotherapy post-induction. AEs (Safety Common Terminology Criteria [v3.0]) and supportive care data were collected while pts were on study. Results: 1093 pts were randomized (545 GC + N Arm, 548 GC Arm); 7 pts in each arm were not treated. 88.3% (GC + N) and 88.0% (GC) pts had a baseline and ≥ 1 post-baseline LCSS assessment. 95% CIs for the hazard ratios (HRs) for time to deterioration (TTD) of all 12 variables contained 1. The HR for TTD of PS by ≥1 point (cycles 1-6) was 0.861 (95% CI: 0.692-1.071). GC + N pts received a median of 6 cycles (interquartile [IQ] range 3-6) of GC, and a median of 6 cycles (IQ range 3-10) of N. GC pts received a median of 5 cycles (IQ range 3-6). Treatment discontinuation rates due to AEs were 13.6% (GC + N) and 14.6% (GC). SAEs were 47.8% (GC + N) and 37.5% (GC). The most common grade ≥3 AE was neutropenia, 24.3% (GC + N) and 27.5% (GC). 51% of GC + N pts continued on N monotherapy (median: 4 additional cycles). Select supportive care for treated patients is summarized in Table below. GC + N (538 pts) (%) GC (541 pts) (%) Concomitant medications 100 100 Transfusions 21.9 20.5 Hospitalizations 41.1 34.0 Colony stimulating factors 13.4 16.8 Erythropoietin 0.2 1.5 Conclusions: Long-term use of N was well tolerated. There were no major differences in AE rates, no detrimental effect overall of adding N to GC in terms of patients' QoL (symptoms and PS). Supportive care and associated resource use were modest. Disclosure: M. Reck: Member of Advisory Board: Hoffmann-La Roche, Lilly, AstraZeneca, BMS, Novartis, Pfizer, Boehringer – Ingelheim Honoraria for lectures: Hoffmann-La Roche, Lilly, AstraZeneca, BMS, Novartis, Pfizer, Boehringer-Ingelheim; M. Dediu: Consultant and Advisory Role (C) - Eli Lilly, Amgen, Boehringer-Ingleheim, Novartis. Speaker fee - TEVA, Boehringer-Ingelheim, MSD, GlaxoSmithkline, Amgen, Astra-Zeneca, Roche, Janssen, Eli Lilly, Pfizer; O. Molinier: Dr Olivier MOLINIER declares -consultant and advisory role for Eli Lilly and Roche -Speaker for Boehringer-Ingleheim; C. Schumann: Consultant and Advisory Role: -Eli Lilly, Pfizer, Roche, Boehringer-Ingelheim Speaker fee: -Eli Lilly, Novartis, Pfizer, Roche, Astra-Zeneca, Amgen, Boehringer-Ingelheim; J. Brown: I am an employee of Eli Lilly and Company and hold stock options and equity with Eli Lilly and Company; V. Soldatenkova: Employment: Lilly Deutschland GmbH, stock ownership. N. Chouaki: Employee of Eli Lilly and Company, I have stock ownership; N. Thatcher: Honoraria for advisory boards and speaker bureaus Eli Lilly and other companies. All other authors have declared no conflicts of interest.

e17652 Background: Advanced squamous non-small cell lung cancer (NSCLC) represents approximately 22% of all lung cancer cases in the US. Although prognosis is generally poor, treatment selection pl...

We report a case of acute nonlymphocytic leukemia, type M4 according to the FAB classification, whose cytogenetics showed trisomy 4 and multiple double minute chromosomes. The patient gave no history of exposure to toxic or carcinogenic substances.