Hold Stock Research Articles

1017P - Phenotypic and functional characterization of tumor infiltrating lymphocytes (TIL) grown from non-hodgkin lymphoma tumors: Implications for the development of novel therapies for lymphoma

Background: Cell therapy with TIL is an effective treatment with acceptable safety profile for advanced metastatic melanoma patients. TIL products can be centrally manufactured for broad clinical application. Adoptive cell therapy with TIL involves collection of autologous lymphocytes from the tumor via surgical resection, ex vivo expansion of TIL, lymphodepletion of the patient prior to infusion of TIL, followed by infusion of TIL and treatment with IL-2. Here, we present findings related to expanding TIL directly from lymphoma. Methods: Using methods for TIL isolation and growth developed at Lion, we expanded TIL from 5/5 lymphoma (1 MCL, 3 follicular, 1 DLBCL) with Interleukin 2 for 11-14 days and subsequent rapid expansion for 14 days using mitogenic anti-CD3 antibody and irradiated allogeneic PBMC. Results: TIL were generated from all 5 lymphoma tumors with a maximum expansion index of 680-fold, significantly higher than previously reported. Mean CD3+ T cell population was 95% (vs 75% previously reported). As with TIL expansion from melanoma, we observed a marked relative increase in effector memory cells in lymphoma TIL. A significant increase in TEMRA (p = 0.0013; CD4, CD8) and CD28+CD4 + (p = 0.008) subsets was observed in lymphoma compared with melanoma TIL cultures. Bioluminescent Redirected Lysis Assay (BRLA) to assess TIL cytolytic activity at 4 hrs ranged from <1-6 LU50 in lymphoma TIL compared to melanoma TIL (11-75 LU50, 4hrs). ELISpot and ELISA analysis revealed IFN-γ production by lymphoma TIL comparable to that of melanoma TIL. Consistent with the observation that lymphoma-reactive T-cells are primarily TH2 and TH17, nanostring analysis revealed that lymphoma TIL expressed higher levels of RORC and IL17A than melanoma TIL. Conclusions: We demonstrate here the feasibility of growing TIL from lymphoma that have effector functions comparable to that of melanoma TIL. These findings serve as a rationale for considering TIL cell therapy for patients with lymphoma. Legal entity responsible for the study: Lion Biotechnologies, Inc Funding: Lion Biotechnologies Inc Disclosure: L. Karyampudi, A. Gokuldass, M. Blaskovich, M.T. Lotze: Employee of Lion Biotechnologies, Inc, receive compensation from Lion. Hold stock and/or stock options in Lion Biotechnologies, Inc. M. Fardis: Employee and director of Lion Biotechnologies, Inc, receive compensation from Lion. Hold stock and/or stock options in Lion Biotechnologies, Inc. Member of the Board of Directors of Lion Biotechnologies, Inc.

Personality Traits and Portfolio Tilts Towards Value and Size

We show that personality traits are related to an investor’s preferences for value versus growth stocks and for small capitalization stocks versus large capitalization stocks. We have detailed personality trait data and official register holdings of stocks for 710 individuals in Finland. The results show that more extravagant individuals tend towards large capitalization growth stocks; more impulsive people tend towards small capitalization growth stocks; more sentimental investors tend towards small capitalization value stocks; and more social investors tend towards small capitalization stocks with a tilt towards value. The results are consistent when looking at the portfolio characteristics across investors, over time, when using aggregate portfolios of investors with similar personality traits, and both widely held and non-widely held stocks.

Equity research and valuation: Jet Airways

Subject area This case helps students to analyze non-financial and financial aspects of a company and observe quantitative and qualitative aspects of decisions and decide whether to invest or not and give suggestions to sell, buy or hold stocks. The case is expected to help the students understand and analyze the following points: the overall performance of the company and industry, how fundamental and technical analysis is applied to reach investment decisions, the areas where Jet Airways occupies the top position compared to peer group (competitor analysis), the company’s financial position and valuation with the help of tools and techniques and suggestions and observations to shareholders whether to buy/sell or hold shares. Study level/applicability This case can be used for MBA (Finance) students on equity research and valuation. Students are introduced to the fundamental procedures of equity research and analysis – evaluating sector desirability, financial modeling, equity valuation methods. To enhance research skills, students are required to acquire basic knowledge on macro and micro economic indicators. This case helps students to analyze non financial and financial aspects of a company and observe quantitative and qualitative aspects of decisions and decide whether to invest or not and give suggestions to sell, buy or hold stocks. Case overview Mr Rahul, a consultant in Karvey brokerage house was about to leave the office on the evening of March 24, 2015 when the phone rang. It was Mr Srirag, one of his clients and close friends who was passionate about investing in shares. Mr Rahul with his two decades of experience in monitoring and advising various investment plans has been continuously advising Srirag on different investments in shares. Srirag said “Rahul! You know that I bought many shares in Jet Airways. While studying the annual reports of Jet Airways 2014-2015 about its business profits and losses, I came across a January to March, 2013 business quarter analysis report that wrote about Jet Airways facing a net loss of 4.95 billion rupees due to over debt burden and interest costs. It also stated that the company sold a 24 per cent stake in 2013 to Etihad for 332$ million which is an Abu Dhabi based airline. The news said that the deal would help the company overcome financial challenges, raise cash, cut costs and gain access to the global flight network. I am worried about whether this deal would allow the company to continue its operations from India or not. I am also concerned about the downfall of Kingfisher, a major setback in the aviation industry in India that owes 8,000 crores to its employees, banks, airports, oil companies. I am worried that either my investment in Jet Airways might bring huge losses or the partnership with Etihad airways would result in the reduction of costs and due to joint sales efforts, sharing resources and network integration thereby leading to a valuable share price. Since your guidance has helped in many issues, I would like to know the present condition and future prospectus prevailing in Jet Airways”. With a lot of ambiguity in his mind, he asked Rahul to recommend if he should hold or sell the shares in Jet Airways. Expected learning outcomes The case is expected to help the students understand and analyze the following points: the overall performance of the company and industry, how fundamental and technical analysis is applied to reach investment decisions, the areas where Jet Airways occupies the top position compared to peer group (Competitor analysis), the company’s financial position and valuation with the help of tools and techniques and suggestions and observations to shareholders on whether to buy/sell or hold shares. Supplementary materials The link to the following videos to be sent to participants in advance to help them prepare for the class. www.youtube.com/watch?v=_3XJXTmILyk, Equity Research Presentation: Coca-Cola, www.youtube.com/watch?v=n5pEK_2uItg Write Equity Research Report, format, process, www.youtube.com/watch?v=mMLJccgiSTk Equity Valuation and Analysis-Part I. Subject code CSS 1: Accounting and Finance.

Antiplatelet Therapy and Clinical Outcomes Following Myocardial Infarction Among Patients in a U.S. Employer-Based Insurance Database.

Estimates of residual cardiovascular risks among patients who have experienced a recent acute myocardial infarction (MI) are predominantly derived from secondary prevention trial populations, patient registries, and population-based cohorts. To generate real-world evidence of antiplatelet treatment and recurrent events following MI in patients on antiplatelet treatment among commercial, employer-based insured patients in a large administrative database. This was a retrospective cohort claims database study using the Truven Health MarketScan Commercial Claims and Encounters and Medicare Supplemental databases between 2007-2011. Patients with an acute MI hospitalization with a discharge date between 2008 and 2010 were included. Excluded were those patients with documentation of stroke, transient ischemic attack (TIA), or severe bleeding at or before index hospitalization and with concomitant use of anticoagulant therapy following index hospitalization. Patients treated with clopidogrel following the index MI hospitalization were followed up to 1 year for repeat MI, stroke, and coronary revascularization. Among 33,943 post-MI continuous clopidogrel users without history of stroke, TIA, or bleeding, 22% had diabetes, whereas angina and renal impairment were less prevalent (5% and 7%, respectively). Over the 1-year follow-up, 2.4% experienced a repeat MI or stroke, and 8.2% underwent coronary revascularization. Angina, diabetes, and renal impairment were associated with elevated 1-year risk of repeat MI or stroke. This study suggests that there is residual cardiovascular risk, although relatively low, in an insured, secondary prevention population on antiplatelet treatment following an MI. In patients with MI, identifying angina, diabetes, and renal impairment may aid risk stratification and guide the effective management of these higher-risk patients. Funding for this research was provided by Merck & Co. Although Merck & Co. formally reviewed a penultimate draft, the opinions expressed are those of the authorship and may not necessarily reflect those of the company. Reed Chase, Wu, Mavros, Heithoff, and Hanson are employees of Merck Sharp & Dohme, a subsidiary of Merck & Co., and may own stock and/or hold stock options in the company. Patel was an employee of Merck & Co. during the conduct of this study and preparation of the manuscript. Simpson is a paid consultant for Merck, Pfizer, and Amgen and has received speaker's fees from Merck and Pfizer. Study concept and design were contributed by all authors except Hanson. Heifhoff and Patel collected the data, and data interpretation was performed by Simpson, Mavros, Patel, Wu, and Hanson. The manuscript was written by Hanson, Mavros, and Patel and revised by Heithoff, Wu, Simpson, and Reed Chase.

Effect of two long-acting treatments, the paliperidone palmitate 1-month and 3-month formulations on caregiver burden in European patients with schizophrenia

IntroductionSchizophrenia puts a significant burden on caregivers.ObjectivesTo explore the effects of two long-acting treatments (LAT), paliperidone palmitate 1-month and 3-month formulations on caregiver burden (CGB) in European patients with schizophrenia using the Involvement Evaluation Questionnaire (IEQ)AimsTo conduct a subgroup analysis of two randomized, double-blind studies (NCT01515423 and NCT01529515).MethodsCaregivers (≥ 1 h of contact/week with the patients) were offered to complete the IEQ (31 items, each scoring: 0–4; total score: sum of 27 items [0–108]).ResultsAmong 756 European caregivers (53% parents, 18% spouse/partner or girl/boyfriend, 10% sister/brother), 60% reported a CGB of ≥ 32 hours/week at open-label baseline (BL-OL). CGB reduced significantly for patients with both BL-OL and at least one double-blind IEQ sum-score (n = 433): mean improvement [SD] (9.9 [12.66], P &lt; 0.001) from BL-OL (mean [SD] 26.0 [13.30]) to study end (16.0 [10.47]); (reduction in burden associated with worrying [2.9 points] and urging [4.3 points]). CGB significantly improved in patients on prior oral antipsychotics post-switching to LAT with less leisure days impacted and less hours spent in caregiving (P &lt; 0.001). There was significant relationship between improvements and relapse status, patient age (P &lt; 0.001), age at diagnosis (P &lt; 0.002), and number of prior psychiatric hospitalizations in the last 24 months (P &lt; 0.05). Prior use of long-acting antipsychotics other than paliperidone palmitate 1-month or 3-month formulations at BL-OL and duration of prior psychiatric hospitalizations in the last 24 months did not show significant effect on improvements.ConclusionSwitching from an oral antipsychotic to an LAT can provide a meaningful and significant improvement in caregiver burden.Disclosure of interestAll authors are employees of Janssen Research &amp; Development, LLC and hold stocks in the company.

Real-World Glycemic Control from GLP-1RA Therapy with and Without Concurrent Insulin in Patients with Type 2 Diabetes.

Glucagon-like peptide 1 receptor agonists (GLP-1RAs) are recommended as add-on therapy in patients with uncontrolled type 2 diabetes (T2D), with no specific guidance as to timing versus insulin. Furthermore, real-world data assessing GLP-1RA outcomes with or without concurrent insulin therapy are lacking. To identify glycemic response with GLP-1RAs by insulin use in patients with T2D at 1-year follow-up to inform decisions regarding GLP-1RA use with or without insulin. This uncontrolled retrospective cohort study included adults with T2D in the Quintiles Electronic Medical Records Database who were newly prescribed GLP-1RA therapy with exenatide once weekly or liraglutide once daily between February 1, 2012, and March 31, 2013 (index period). Primary outcomes were change in hemoglobin A1c (A1c) at 1 year and attainment of A1c < 7%, < 8%, and < 9%. Results were stratified by baseline insulin use, which was defined as no insulin use at baseline, insulin initiated with a GLP-1RA on index date, and insulin prescribed before starting GLP-1RA therapy. Secondary outcomes included 1-year weight, low-density lipoprotein cholesterol (LDL-C), and blood pressure outcomes for the study population. Adjusted mean (marginal) change in A1c at 1 year was estimated using multivariate linear regression, and multivariate logistic regression was used to estimate the likelihood of patients attaining A1c < 7% at follow-up, controlling for potential confounders. This study included 5,141 patients with a mean (SD) age of 57.0 (10.9) years, 53.5% of whom were females, and with a mean baseline A1c of 8.4% (1.6). Overall, 35.4% had no baseline insulin use, 42.9% were prescribed insulin before starting GLP-1RA therapy, and 21.7% were started on insulin with a GLP-1RA. The adjusted mean A1c reduction at 1 year was 0.75% (95% CI = -0.86 to -0.63) for patients initiating insulin on index date, 0.61% (95% CI = -0.70 to -0.51) for patients with no baseline insulin use, and 0.23% (95% CI = -0.33 to -0.13) for patients prescribed insulin before GLP-1RA therapy. Patients with no baseline insulin or who coinitiated insulin and a GLP-1RA were more likely to attain A1c < 7% at follow-up versus patients prescribed insulin before initiating GLP-1RA therapy (OR = 1.50, 95% CI = 1.08 to 2.09 and OR = 1.85, 95% CI = 1.30 to 2.62, respectively). At 1-year follow-up, significant improvements in weight, LDL-C, and blood pressures were also observed. GLP-1RA therapy was associated with significant improvements in glycemic control when used with or without insulin, as well as reductions in weight and LDL-C overall. However, greater A1c reductions and a higher likelihood of attaining A1c goal levels were observed when a GLP-1RA was initiated alone or with insulin than when a GLP-1RA was added to a regimen that included insulin. GLP-1RA therapy is an effective treatment option when used with or without insulin and may be considered in patients with uncontrolled glycemia. The study was funded by a collaborative research grant from AstraZeneca. Employees of AstraZeneca participated in most aspects of the study and in manuscript preparation. Nguyen and Hurd are employed by, and hold stock in, AstraZeneca. McAdam-Marx reports participation in the AMCP Diabetes Partnership and has stock ownership in GlaxoSmithKline. Study concept and design were contributed by Nguyen, McAdam-Marx, and Singhal, along with Unni and Schauerhamer. Singhal, Unni, Nguyen, and McAdam-Marx collected the data, with assistance from Schauerhamer and Hurd, and data interpretation was performed by Unni, Hurd, McAdam-Marx, Singhal, Nguyen, and Schauerhamer. The manuscript was written by Singhal, Schauerhamer, Unni, and McAdam-Marx, along with Nguyen and Hurd, and revised by McAdam-Marx, Singhal, Unni, and Nguyen, along with Schauerhamer and Hurd.

Impact of Out-of-Pocket Pharmacy Costs on Branded Medication Adherence Among Patients with Type 2 Diabetes.

Medication adherence is pivotal for the successful treatment of diabetes. However, medication adherence remains a major concern, as nonadherence is associated with poor health outcomes. Studies have indicated that increasing patients' share of medication costs significantly reduces adherence. Little is known about a potential out-of-pocket (OOP) cost threshold where substantial reduction in adherence may occur. To examine the impact of diabetes OOP pharmacy costs on antihyperglycemic medication adherence and identify the potential threshold at which significant reduction in adherence may occur among patients with type 2 diabetes mellitus (T2DM). This was an observational, retrospective cohort study using longitudinal U.S. pharmacy and medical claims data from the IMS Health Medical Claims (Dx) database. Patients with T2DM who initiated therapy with a branded antihyperglycemic medication during the index period (January 1, 2011, to December 31, 2011) and had 3 years of follow-up data were included. The primary outcome was adherence to antihyperglycemic medications, measured as the number of days covered. Propensity scores were calculated using baseline sociodemographic and clinical characteristics to control for potential confounding factors. Four strata were created based on mean propensity scores. Across each stratum, patients were assigned to 5 diabetes OOP pharmacy (including generics) cost levels: $0-$10, $11-$40, $41-$50, $51-$75, and > $75. Multivariate regression models were used to estimate association of diabetes OOP pharmacy costs and adherence for each stratum. Sensitivity analyses were conducted to assess the impact of total OOP pharmacy costs and index drug category OOP costs on adherence. A total of 15,416 patients were assessed. Across each stratum in the diabetes OOP pharmacy cost analysis group, mean patient age ranged from 52.3 to 56.1 years, mean number of antihyperglycemic medication classes ranged from 1.5 to 3.2, and mean household income ranged from $60,763 to $79,373. Most patients used a commercial plan (55%-85%). The propensity-stratified multivariate regression model revealed an overall negative relationship between diabetes OOP pharmacy costs and adherence across several OOP cost levels. Diabetes OOP pharmacy cost level $51-$75 appeared as the threshold at which adherence reduced significantly (77-78 fewer days of coverage over 3 years of follow-up; P < 0.05) when compared with the lowest OOP costs ($0-$10) across all strata. Adherence reduced further (99-145 fewer days of coverage; P < 0.0001) for the higher diabetes OOP pharmacy cost levels (> $75) when compared with the lowest OOP cost levels. Sensitivity analyses with total OOP pharmacy costs and index drug category OOP costs revealed negative association with adherence across all strata. Diabetes OOP pharmacy cost was negatively associated with patient adherence, and a potential OOP cost threshold ($51-$75) was identified at which adherence reduced significantly. The study findings may be beneficial in informing the design of health care plans to achieve optimal adherence and improve disease management in patients with T2DM. This study was funded by Eli Lilly and Company. Eli Lilly and Company was involved in the study design; collection, analysis, and interpretation of data; preparation of the manuscript; and decision to submit for publication. Fu is an employee of Eli Lilly and Company. Taylor and Kwan are employees of Lilly USA. Fu and Kwan hold stock or stock options in Eli Lilly and Company. Bibeau was an employee of Eli Lilly and Company at the time of this study and initial submission of this manuscript. Bibeau is currently employed by Janssen Scientific Affairs. The abstract for this study was presented at the AMCP Managed Care & Specialty Pharmacy Annual Meeting 2016; April 19-22, 2016; San Francisco, California. Bibeau and Fu contributed to the study design and collected the data. All authors contributed equally to data interpretation and manuscript preparation and revision.

Impact of gonadotropin type on progesterone elevation during ovarian stimulation in GnRH antagonist cycles.

Does hormonal stimulation with corifollitropin alpha (CFA) only, mimicking a step down protocol, result in lower incidence of progesterone elevation on the day of hCGtrigger as compared to sustained stimulation with recombinant FSH (rFSH)? The current findings support the concept that sustained FSH stimulus contributes to premature progesterone elevation in stimulated IVF cycles. Serum progesterone rise during the follicular phase of ovarian stimulation for IVF treatment seems to be related to a poorer reproductive outcome. However, the mechanism by which the rise in progesterone is caused is not yet fully understood. This study was a post hoc analysis of data from two multi-center, randomized, double-blind, double-dummy, active-controlled, non-inferiority trials, ENGAGE and PURSUE, conducted from June 2006 to January 2008 and from July 2010 to October 2012 respectively. In the ENGAGE-study, 1506 women, aged 18-36 years, were allocated to either a single injection of 150 mg CFA or daily injections of 200 IU rFSH in the first week of stimulation, using a standard GnRH antagonist protocol. In the PURSUE-study, a total of 1390 women, aged 35-42 years, were allocated to either a single injection of 150 mg of CFA or daily 300 IU of rFSH for the first week, again using a standard GnRH antagonist protocol. In both trials, daily rFSH was continued until three follicles reached >17 mm in size. All women had a body weight of between 50 and 90 kg, regular menstrual cycles and an indication for ovarian stimulation before IVF. The incidence of progesterone elevation on day of hCG-trigger in patients with CFA only or rFSH stimulation, and triggered on Day 8 of stimulation, was analyzed. Of patients with CFA only stimulation, 5.4% (13/239 patients) showed a progesterone elevation above 1.5 ng/ml on day of hCG-trigger, whereas patients with rFSH stimulation had a significant higher incidence of progesterone elevation (18.3%; 62/339 patients) (P<0.001). Post hoc analysis of data from previously published trials could be considered as a reason for caution. Future studies should evaluate whether it would be possible to prevent a premature progesterone rise in cycles stimulated with daily FSH by using a step down protocol towards the end of the follicular phase. Financial/Material Support was provided by Merck & Co., Inc., Kenilworth, NJ, USA. Davis Gates is an employee of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA and may own stock and/or hold stock options in the company. Fabiola Beligotti is an employee of MSD, Italy, a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA and may own stock and/or hold stock options in the company. Barbara Lawrenz, Nils Engelmann and Human M. Fatemi have no conflict of interest. ENGAGE study: ClinicalTrials.gov identifier NTC00696800. PURSUE-study: NCT01144416.

Economic Burden of Illness Among Patients with Severe Asthma in a Managed Care Setting.

Despite intensive pharmacotherapy, a considerable number of patients with severe asthma have inadequate disease control. Patients with severe asthma who experience exacerbations consume significant health care resources. To assess health care resource utilization and associated costs among patients with persistent severe asthma who experienced exacerbations compared with patients with persistent but nonsevere asthma. This retrospective analysis of a national administrative claims database identified patients aged ≥ 12 years who had at least 1 medical claim with an asthma diagnosis in 2012 and had continuous medical and pharmacy coverage under a commercial or Medicare Advantage plan from January 1, 2012, to December 31, 2013. Patients were assigned to 1 of 2 mutually exclusive cohorts-persistent asthma (PA) or severe asthma (SA)-according to an established algorithm based on asthma-related health care resource use and pharmacy claims for controller medication. SA patients were required to meet PA criteria and also have evidence of ≥2 asthma exacerbations in 2012. Asthma-related health care resource utilization and costs were computed from asthma medication use (rescue and controller therapy) and medical claims with an asthma diagnosis in the primary position in 2012 and 2013. Adherence to controller therapy was assessed over 365 days by using the proportion of days covered (PDC), starting with the first claim for controller therapy in 2012. Differences between the PA and SA cohorts were analyzed by t-test for continuous variables and chi-square test for categorical variables. Asthma-related costs in 2013 were also analyzed using a generalized linear model with a gamma distribution and log link, adjusted for patient demographics (age, gender, region, and insurance type) and Quan-Charlson comorbidity score. A total of 65,359 patients were included: 63,597 (97.3%) PA patients and 1,762 SA patients (2.7%). Compared with the PA cohort, the SA cohort was older (mean age = 50.8 years vs. 46.5 years, P < 0.001) and had higher mean comorbidity score (1.47 vs. 1.31, P< 0.001). The mean count of all asthma medications fills was 2.2-fold (2012) and 2.1-fold (2013) higher in the SA cohort, compared with the PA cohort (P< 0.001). Mean PDC for all oral and inhaled controller therapy was also higher in the SA cohort compared with the PA cohort (0.80 vs. 0.65, P< 0.001). SA patients had a significantly greater mean count of asthma-related hospitalizations, emergency room visits, and ambulatory visits in 2012 and 2013 (P< 0.001). Unadjusted mean annual asthma-related costs in the SA versus PA cohorts were $6,496 versus $2,739 (P < 0.001) in 2012 and $5,174 versus $1,775 (P< 0.001) in 2013. Higher asthma-related costs were driven by greater mean annual asthma medication costs in 2012 ($4,545 vs. $1,738, P< 0.001) and 2013 ($4,068 vs. $1,348, P< 0.001). Adjusted mean annual asthma-related costs in 2013 were $3,336 greater (cost ratio=2.878, P< 0.001) in the SA cohort, and adjusted mean annual asthma medication costs were $2,672 higher (cost ratio=2.982, P< 0.001) in the SA cohort. Patients with SA who experienced 2 or more exacerbations had 2.1-fold greater use of controller medications across both study years and were more adherent to controller therapy than patients with PA. Despite more intensive pharmacotherapy, SA patients incurred 2.9-fold higher adjusted asthma-related costs and 3-fold higher adjusted asthma medication costs than PA patients. Patients with SA consistently demonstrated a higher rate of health care utilization. Funding for this study (HO-14-14443) was provided by GlaxoSmithKline (GSK). All listed authors meet the criteria for authorship set forth by the International Committee for Medical Journal Editors. Albers, Forshag, and Yancey are employees of GSK and hold stock in GSK. Dalal, Nagar, and Ortega were employees of GSK at the time this research was conducted. Chastek and Korrer are employees of Optum, which received consulting fees from GSK for research related to this study. Study concept and design were contributed by Chastek, Nagar, and Dalal. Korrer took the lead in data collection, along with Chastek, and data interpretation was performed by Chastek, Ortega, Forshag, and Dalal. The manuscript was written by Chastek and Dalal and revised by Albers and Yancy, assisted by the other authors.

Real-World Axitinib Use in the United States: A Retrospective Study Using Linked Datasets.

Axitinib is approved by the FDA for the treatment of advanced renal cell carcinoma (RCC) after failure of 1 previous systemic therapy and is distributed primarily through specialty pharmacies. Although the efficacy and safety of axitinib have been established in clinical trials, information from real-world populations will help to elucidate patients' clinical profiles and utilization patterns. Prescription records alone provide limited information on patient characteristics and other treatment experiences. Expansion of these data with information from medical claims databases should yield observational real-world data that may help to optimize therapy for patients with advanced RCC. To link information from a specialty pharmacy database with information from medical and pharmacy claims databases to characterize real-world treatment patterns of axitinib as subsequent systemic therapy in patients with RCC in the United States. This retrospective, observational, cohort study linked de-identified patient-level data from 22 specialty pharmacies that dispense axitinib with databases of longitudinal medical and pharmacy claims. Eligible patients had a diagnosis of RCC (> 1 claim for RCC defined as ICD-9-CM code 189.0), previously received > 1 systemic therapy, had the first prescription for axitinib dispensed between May 2012 and April 2013 (index), and had consistent claims reporting by pharmacies and physicians. All treatment data were used to calculate cycle, line of therapy, and duration of therapy; prescription data were used to determine axitinib dose modifications. Multivariate and logistic regression analyses were conducted to assess the effect of patient/prescriber characteristics on duration of axitinib therapy and dose modifications, respectively. In all, 1,175 patients met the study inclusion criteria and had data present in specialty pharmacy and claims databases. Most patients (74%) were male, and 68% were aged 55-74 years. Mean (SD) Charlson Comorbidity Index score was 2.7 (± 1.1); the most common comorbidity was hypertension (in 199 patients, 17%). Based on Rx-Risk-V, the most frequent concomitant conditions were pain (40%) and ischemic heart disease/hypertension (30%); the most frequent concomitant medications were antihypertensive medications (46%) and opiates (40%). Most prescribers (63%) were affiliated with an academic center, and all U.S. geographic regions were represented. In all, 847 patients (72%) had commercial insurance. Axitinib was prescribed as second-line therapy in 659 patients (56%), as third-line therapy in 326 patients (28%), and as fourth-line or later therapy in 190 patients (16%). In the overall population, mean (SD) duration of axitinib therapy was 168.6 (± 148.4) days. Axitinib treatment duration was 21 days longer in males than females (P = 0.013); 28 days longer in patients in the Northeast than in the Midwest or West (P = 0.010 and P = 0.016, respectively); and 26 days longer in patients receiving baseline hypothyroidism treatment (P = 0.004). In patients receiving second-line axitinib, the most common first-line therapy was sunitinib (56%), followed by pazopanib (16%) and everolimus (12%). Mean (SD) duration of second-line axitinib treatment was 172.3 (± 150.6) days and ranged from 127 days in patients who previously received temsirolimus to 196 days in those who previously received sorafenib. Of 1,025 patients who initiated axitinib at the standard 5 mg twice daily starting dose, 70% remained at this dose throughout treatment, whereas 10% had a dose increase. Younger age and gender (male) were associated with dose increases (OR = 0.958, 95% CI = 0.941-0.975 and OR = 0.573, 95% CI = 0.364-0.903, respectively). Baseline hypothyroidism treatment was associated with dose decreases and increases (OR = 1.662, 95% CI = 1.088-2.539 and OR = 2.149, 95% CI = 1.353-3.413, respectively). This analysis demonstrates the feasibility and utility of linking specialty pharmacy data to other longitudinal databases to better understand patient, provider, and reimbursement characteristics. These data provide insight into routine clinical use of axitinib as subsequent RCC therapy in the United States in the period following FDA approval, as well as additional information on sequencing of targeted agents in patients with advanced RCC. This study was sponsored by Pfizer. MacLean and Cisar are employees of and hold stock in Pfizer. At the time of this analysis, Mehle, Eremina, and Quigley were employees of IMS Health who were paid consultants to Pfizer during the conduct of this study and in connection with the development of this manuscript. MacLean and Cisar contributed to study design and manuscript development. Mehle, Eremina, and Quigley contributed to study design, analysis, and manuscript development.

The Pharmacokinetics of Pregabalin in Breast Milk, Plasma, and Urine of Healthy Postpartum Women.

Limited data exist on the presence of pregabalin in human breast milk of nursing mothers. This study aimed to determine pregabalin concentrations in breast milk, estimate the infant daily pregabalin dose from nursing mothers, and evaluate pregabalin pharmacokinetic data in lactating women (≥ 12 weeks postpartum). In this multiple-dose, open-label, pharmacokinetic study, 4 doses of pregabalin 150 mg were administered orally at 12-hour intervals. Urine, blood, and breast milk samples were collected up to 12, 24, and 48 hours, respectively, following the fourth dose. Pharmacokinetic parameters were estimated using noncompartmental methods. Adverse events were monitored throughout. Ten healthy lactating women (age 24-37 years) received pregabalin. Geometric mean pregabalin Cmaxss and AUCτ values in breast milk were approximately 53% and 76%, respectively, of those for plasma. The mean amount of pregabalin in breast milk recovered in a 24-hour period after the last dose was 574 μg (range, 270-1720 μg), which is approximately 0.2% of the administered daily maternal dose of 300 mg. The estimated average daily infant dose of pregabalin from breast milk was 0.31 mg/kg/day, which would be approximately 7% (23% coefficient of variation) of the body weight normalized maternal dose. Approximately 89% of the dose administered was recovered in urine. Renal clearance averaged 68.2 mL/min. Adverse events were of mild or moderate severity. Lactation appears to have had little influence on pregabalin pharmacokinetics. Overall, the estimated dose of pregabalin in breastfed children of women receiving pregabalin is low. Pregabalin was well tolerated in lactating women. The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Peter A. Lockwood, Lynne Pauer, Joseph M. Scavone, Maud Allard, Laure Mendes da Costa, Tanja Alebic-Kolbah, Anna Plotka, Christine W. Alvey, and Marci L. Chew were all full-time employees of Pfizer at the time the study was completed and hold stock and/or stock options in Pfizer. The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This study was sponsored by Pfizer, which was involved in the study design, the collection, analysis, and interpretation of the data, the writing of the report, and the decision to submit the paper for publication. Medical writing support was provided by Penny Gorringe, MSc, of Engage Scientific Solutions and funded by Pfizer.

Investor’s Disposition Error at Emerging Market: Evidence for Experiential and Rational Thinking Styles

This study aims to examine the role of two information processing styles toward investor’s disposition errors. This experimental study used a full factorial design 2 x 2 x 2 (two decision outcomes: negative and positive, two types of action: inaction (hold stock) and action (sell stock), two information processing styles: rational and experiential styles. The subjects in this experiment consisted of 181 participants. The experimental results conclude several important findings. First, there was a significant interaction of information processing styles, types of action, and decision outcomes in shaping degree of participant’s satisfaction/regret in investment decisions. Interestingly, when the decision outcome was negative (actual loss) and type of action was to hold losing stock, degree of regret was higher for subjects who were in an experiential styles than rational thinking styles. Likewise, when decision outcome was positive (missed loss) and type of action was to hold stocks, degree of satisfaction was higher for subjects who were in an experiential style rather than rational thinking styles. Second, the result of this study indicated that the emotion of satisfaction/regret was more predominant on subjects who were in an experiential thinking style than a rational thinking style. This result revealed that disposition error was greater on subjects who were in an experiential style than a rational thinking styles. DOI: 10.5901/mjss.2015.v6n5p313

288P - Impact of the 21-Gene Breast Cancer Assay on Treatment Recommendations for Estrogen Receptor-Positive (Er+) Early Stage Breast Cancer (Esbc) in Hong Kong

ABSTRACT Aim: The 21-gene breast cancer assay has been validated to assess risk of distant recurrence and the likelihood of chemotherapy (CT) benefit in ER+ ESBC patients in a number of different populations. In Hong Kong >80% of breast cancers are ESBC and >60% of these women receive CT. The assay's impact on adjuvant treatment recommendations has not been reported in a Chinese population. This prospective decision impact study measured changes in physician treatment recommendations in this new population of patients. Methods: Eligible patients from 6 institutions had ER + , T1-3 N0-1mi M0 ESBC. After surgery, physicians discussed treatment options with patients, then ordered the assay. After receipt of the result the treatment recommendation was reassessed. Changes in treatment recommendation, CT utilization, and physician confidence were measured, as was physician rating of influence on their recommendation. Results: One hundred fifty consecutive patients were enrolled. Four were not evaluable. The remaining 146 eligible patients had treatment recommendations before and after testing. CT recommendations, which included changes in CT intensity, were changed for 34/146 patients, (23.3%, 95% CI 16.7%-31.0%). There were 27 changes in treatment recommendations of adding or removing CT altogether (18.5% change, 95% CI 12.6%-25.8%). CT recommendations decreased from 52.1% to 37.7%, a net reduction of 14.4% (p Conclusions: The primary outcome suggests that the 21-gene breast cancer assay influences adjuvant treatment recommendations by physicians in Hong Kong for their patients with ESBC. Disclosure: R. Leung, T. Yau and P. Cheung:: We received financial support from Genomic Health, Inc. for the conduct of this study. I have no other conflicts of interest to declare; C. Chao: I am an employee and hold stock shares in Genomic Health which develops and commercializes the Oncotype DX assay; C. Yoshizawa: I am an employee and hold stock shares in Genomic Health which develops and commercializes the Oncotype DX assay.

Pharmacokinetics, Safety and Tolerability of Cyclosporine or Tacrolimus Following Coadministration of ABT-450/r, ABT-267 and ABT-333 in Healthy Subjects.

ABT-450,a NS3 protease inhibitor,(dosed with low-dose ritonavir,ABT-450/r) identified by Abbott and Enanta,ABT-267,a NS5A inhibitor and ABT-333,a NS5B polymerase inhibitor are directly acting antivirals (DAAs) being developed for the treatment of HCV infection.The effect of DAA combinations on the pharmacokinetics,safety and tolerability of cyclosporine A (CsA) or tacrolimus was assessed in 72 healthy subjects.Figure: No Caption available.Pharmacokinetic sampling: CsA &/or DAA: Day 1 (Period 1), Days 1,14-21 (Period 2). Tacrolimus &/or DAA: Day 1 (Period 1), Days 14-21 (Period 2).The magnitude of interaction between the DAAs and CsA or tacrolimus was comparable across all arms.CsA+DAAs: On Day 15, CsA dose-normalized (DN) AUCinf and DNC24 were 4-6 fold and 13-16 fold, respectively, of CsA exposures when CsA was administered alone.CsA DNCmax was not affected,while t½ increased from 7 to 24 hrs.ABT-450 exposures increased by 12-72% while ABT-333 exposures decreased by 30-34%. ABT-267 and ritonavir exposures were not affected.Tacrolimus+DAAs: On Day 15,tacrolimus DNAUCinf, DNCmax and DNC24 were 57-86 fold, 3.7-4.3 fold and 17-25 fold of tacrolimus exposures when tacrolimus was administered alone,while tacrolimus t½ increased from 29-32 to 232-253 hrs.ABT-450, ABT-333 and ritonavir exposures decreased by 11-51% while ABT-267 exposures were not affected.Adverse events were infrequent and mostly mild,and were consistent with those seen with DAAs,CsA or tacrolimus dosed alone.Concentration-time profiles from these interactions were used to predict dose frequencies that would provide optimal CsA and tacrolimus levels using simulations.When co-dosed with the combination DAA regimens,subjects on CsA should reduce the total daily CsA dose to approximately 1/5th-1/10th of their previous maintenance dose,while subjects on tacrolimus should modify the total daily tacrolimus dose to 0.5 mg/week to maintain Ctrough similar to those prior to DAA co-administration,with appropriate clinical monitoring.These recommendations are being validated in a clinical trial in HCV genotype 1 infected post-transplant subjects on the 3DAA regimen with ribavarin for 24 weeks. DISCLOSURES:Badri, P.: Grant/Research Support, Study desinged, conducted and sponsored by Abbvie, Employee, Full time employee of Abbvie, Stockholder, Hold Abbvie stock or stock option. Cohen, D.: Grant/Research Support, Study designed, conducted and sponsored by Abbvie, Employee, Full time employee of Abbvie, Stockholder, Hold Abbvie Stocks or stock options. Ding, B.: Grant/Research Support, Study designed, conducted and sponsored by Abbvie, Employee, Full time employee of Abbvie, Stockholder, Hold Abbvie stocks or stock options. Podsadecki, T.: Grant/Research Support, Study designed, conducted and sponsored by Abbvie, Employee, Full time employee of Abbvie, Stockholder, Hold Abbvie stocks or stock options. Bernstein, B.: Grant/Research Support, Study designed, conducted and sponsored by Abbvie, Employee, Full time employee of Abbvie, Stockholder, Hold Abbvie stocks or stock options. Awni, W.: Grant/Research Support, Study designed, conducted and sponsored by Abbvie, Employee, Full time employee of Abbvie, Stockholder, Hold Abbvie stocks or stock options. Dutta, S.: Grant/Research Support, Study designed, conducted and sponsored by Abbvie, Employee, Full time employee of Abbvie, Stockholder, Hold Abbvie Stocks or stock options. Menon, R.: Grant/Research Support, Study designed, conducted and sponsored by Abbvie, Employee, Full time employee of Abbvie, Stockholder, Hold Abbvie stocks or stock options.

WS10.1 Can home drug audit prevent oversupply and indicate adherence?

Objectives: Following deaths of 2 CF patients, relatives returned drugs valued €4,443 and €3,631. 1 had >100 days supply of pulmozyme and stocks of 7 drugs which had date expired. In clinic, CF patients claim non-adherence with drugs because stocks have run out. In 2014, CF centres in England will take over all prescription of high cost nebulised drugs (HCND). Would it be cost efficient to assess home drug stocks to prevent oversupply, wastage and to help assess adherence? Methods:We administered a questionnaire and undertook home visits to 27 patients attending our CF centre to audit their drug stocks. Results: Patients were prescribed 2−23 drugs (median 13), and held stocks of 2−27 drugs. 1% of all drugs were date expired. 15% drugs were no longer prescribed (7.7% by value) of which 82% by value were antibiotics. For 19% drugs, patients held >10 weeks supplies. 37/369 prescriptions were for HCND. For HCND, no patient held >2 months supply. Patients held no home stocks for 15% of prescribed drugs. 18/27 patients lacked stocks of at least 1 prescribed drug. Some held no stocks of 43% of their prescription. Patients held no home stocks for 9/37 (24%) HCND. Lack of home stocks was not correlated with FEV1 or educational level. Many patients had poor awareness of levels of stocks. One patient predicted 7 days, but had median 88 days; another predicted 84 days, but had 7.5 days. 62% patients reported having previously run out of medications; yet 7/10 patients who reported never having run out, held no home stocks of at least 1 prescribed drug. Conclusion: Home drug audits offer no cost savings with HCND. Visits may identify patients who lack stocks and so are non adherent.

An Intermarket Approach to Tactical Risk Rotation: Using the Signaling Power of Treasuries to Generate Alpha and Enhance Asset Allocation

Numerous academic studies have shown that asset allocation is the single most important determinant of portfolio returns. We accept this premise but note that an optimal asset allocation strategy must still be determined based on dynamic conditions. Using the principles of intermarket analysis and the relationship between the total return of the 10-year Treasury and the 30-year Treasury, we develop one such strategy. We find that an active strategy that uses the signaling power of these Treasury bonds to position into either the stock market or Treasuries can be used to outperform a buy and hold stock portfolio on an absolute and risk-adjusted basis. We also find that the signaling power of Treasuries can be used to enhance asset allocation decisions and traditional rebalancing. The predictive behavior of Treasuries on equities is a market anomaly that has persisted over time, and has served as an anticipatory gauge of expansionary or contractionary conditions which favor stocks or bonds. Contrary to the Efficient Market Hypothesis, the information provided by relative total return Treasury movement does not appear to be priced in immediately by broad stock market averages, and therefore may be exploitable for active traders and tactical asset allocators.

대규모 기업집단의 순환출자 해소를 위한 휴리스틱 기법

Circular shareholding is established when at least three member firms in a business group hold stock in other member firms and form a series of ownership in a circular way. Although there have been many studies which inves-tigated a negative effect of circular shareholding on firm‘s va lue, few studies have discussed how to resolve the problem given complicated ownership structures of large business groups .This paper is based on a mixed integer programming model, which was proposed in the author’s previous research and can identify the ownership share divested in order to resol ve circular shareholding. Since the optimization model becomes too complicated for large business groups and requires a sophisticated software to solve it, we propose a simple heuristic method that can find a good approximate soluti on to the model. Its applications to twelve Korean large business groups show that the heuristic method is not jus t computationally attractive but also provides near-opti-mal solutions in most cases.

Ofatumumab + Chlorambucil Versus Chlorambucil Alone In Patients With Untreated Chronic Lymphocytic Leukemia (CLL): Results Of The Phase III Study Complement 1 (OMB110911)

Abstract Introduction Chemoimmunotherapy with purine analogues and the anti-CD20 antibody rituximab is the standard of care as initial therapy in younger and physically fit patients with chronic lymphocytic leukemia (CLL). However, most CLL patients are elderly and/or have comorbidities, meaning that fludarabine-containing regimens are often inappropriate, carry greater toxicity, and treatment of these patients remains challenging. Most randomized studies in previously untreated CLL have been conducted in younger or fit patients and results cannot necessarily be extrapolated to older, less fit patients. While chlorambucil (CHL) remains a standard of care for this patient population, more effective but tolerable treatment choices are still needed. Ofatumumab (O) demonstrated superior preclinical activity, compared to rituximab, against cells with low CD20 density like CLL and showed clinical activity as monotherapy, with high overall response rates (ORR) in patients with refractory CLL. Therefore, the addition of O to CHL could provide superior clinical outcomes than CHL alone, while being tolerable, for patients who are elderly and/or have comorbidities and currently have limited treatment options. Methods Patients with CLL who required therapy (2008 NCI-WG guidelines) and were considered inappropriate for fludarabine-based therapy due to advanced age and/or co-morbidities were randomized (1:1) to receive either O+CHL or CHL. CHL was given orally (10mg/m2 at days 1-7 of each 28 day cycle) and O was administered as intravenous infusions (Cycle 1: 300mg day 1 and 1000mg day 8, subsequent cycles: 1000mg at day 1). O premedication included acetaminophen, antihistamine and glucocorticoid. Treatment duration was a minimum of 3 cycles, until best response up to a maximum of 12 cycles. The primary endpoint was progression-free survival (PFS) assessed by an Independent Review Committee (IRC) and secondary endpoints included overall response rate (ORR), overall survival (OS) and safety. Patients 447 patients from 16 countries were randomized. Baseline demographics and disease characteristics were well balanced between the 2 arms. Median age was 69 years with 82% ≥65 years and/or having ≥2 comorbidities. All modified Rai stages were represented (Low 8%, intermediate 51%, high 40%). 56% of patients had unmutated IgVH, 6% showed 17p deletions and 75% had β-2-microglobulin levels ≥3500μg/L. Results PFS as assessed by an IRC was significantly prolonged in the O+CHL arm (22.4 months) compared to CHL alone (13.1 months, p&lt;0.001). ORR was higher for O+CHL vs CHL (82% vs 69%, p=0.001), with a superior CR rate (12% vs 1%). 37% of O+CHL subjects with an IRC-assessed CR were MRD negative. With a median follow-up of 29 months, median OS was not reached for O+CHL or CHL. Median duration of treatment for both arms was 6 cycles and 82% of patients received 6 or more cycles of O+CHL. Grade ≥3 AEs that occurred from start of treatment until 60 days after the last dose were experienced by 50% of patients receiving O-CHL and 43% of patients on CHL with the most common being neutropenia (O+CHL: 26%, CHL: 14%). Grade ≥3 infusion-related AEs were reported in 10% of patients. No fatal infusion reactions were reported. Grade ≥3 infections were reported in 15% (O+CHL) and 14% (CHL) of patients, with the most common infection being pneumonia (O+CHL: 4%, CHL: 3%). Deaths during treatment occurred in 2% of subjects in both arms. Conclusion Ofatumumab added to chlorambucil (O+CHL) demonstrated clinically important improvements with a manageable side effect profile in patients with CLL who have not received prior therapy and who are considered inappropriate for fludarabine based therapy. Disclosures: Hillmen: Roche Pharmaceuticals: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Pharmacyclics: Research Funding; Celgene: Honoraria; GlaxoSmithKline: Honoraria, Research Funding. Off Label Use: The use of ofatumumab in combination with chlorambucil in previously untreated CLL. The reported trial will support the extension of the ofatumumab licence. Robak:GlaxoSmithKline: Honoraria, Research Funding. Janssens:GlaxoSmithKline: Speakers Bureau; Roche: Speakers Bureau; Mundipharma: Speakers Bureau; Amgen: Speakers Bureau. Mayer:Glaxo: Consultancy, Research Funding; Roche: Consultancy, Research Funding. Panagiotidis:Novartis: Consultancy, Honoraria; Roche: Consultancy, Honoraria; GSK: Consultancy, Honoraria. Kimby:Pharmacyclics: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding; Teva: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding; Mundipharma: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding; Roche: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding; Emergent: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding. Schuh:GSK: Honoraria, Research Funding. Montillo:Janssen: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding; Mundipharma: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding; GSK: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding; Roche: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding. McKeown:GSK: Employment. Carey:GlaxoSmithKline: Employment. Gupta:GSK: Employment. Chang:GSK: Employment. Lisby:Genmab: Employment, hold stock options Other. Offner:Lilly: Membership on an entity’s Board of Directors or advisory committees.

Shareholders' Agreements in Listed Companies: Germany

In Germany, shareholders’ agreements were discussed primarily as a company law issue but are of practical importance also in listed companies. Shareholders’ agreements occur primarily in family held stock corporations but are at least not disclosed in all firms with different family members as shareholders. Forms of shareholders’ agreements are: shareholder voting agreements (Stimmbindungsvertrage), pooling of shares, mutual understanding. Legally, shareholders’ agreements are treated as civil partnership, according to the German Federal Supreme Court shareholders’ agreements are non-disclosed or internal civil partnerships. The application of the rules on partnerships does not transfer the majority requirements from the stock corporation to the decision-making in the shareholders’ agreement. The general rule of unanimous decision-making might be transformed to simple majority voting but restrictions of the selling of shares by members of the agreement are to be controlled by the courts, selling clauses have to provide for a fair value, not necessarily the exact market price.For listed companies, transparency could (and should) be enhanced with a duty not only to name a figure for the shares held, but also the shareholders’ agreement itself. Further, it seems appropriate to publish also the majority voting rules in the shareholders’ agreement. The same would apply, if the shareholders would transform their shares into a limited liability company. For outside shareholders, unanimous or majority voting in the shareholders’ agreement might make a difference.

1225O - A Randomized Phase 2 Study of Erlotinib Plus Pemetrexed vs Erlotinib or Pemetrexed Alone as Second-Line Treatment for Never-Smoker Patients with Non-Squamous Advanced Non-Small Cell Lung Cancer (NSCLC)

ABSTRACT Background Erlotinib (E) and Pemetrexed (P) are approved second-line treatments in patients (pts) with relapsed NSCLC and may be effective in combination. This randomized phase 2 study compared the efficacy and safety of E + P vs either agent alone, as second-line treatment in never-smoker pts with advanced non-squamous NSCLC. Methods From Nov 2007 to Jul 2010, never-smoker NSCLC, ECOG Performance Status (PS) ≤2 pts who had failed 1 prior chemotherapy regimen were enrolled and randomized to either: E 150 mg daily, P 500 mg/m2 day 1, or P 500 mg/m2 day 1 plus E 150 mg daily on days 2 to 14 of a 21-day cycle, continued until discontinuation criteria were met. The primary endpoint of progression-free survival (PFS) was analyzed using a sequential approach. A multivariate Cox model was used to perform a global comparison across the 3 arms with pairwise comparisons between treatments using contrasts within the model. If the global null hypothesis was rejected at a 2-sided 0.2 significance level (SL), then 2 pairwise comparisons of E + P vs E or P were conducted. Statistical significance was claimed if both pairwise and global null hypotheses were rejected at a 2-sided 0.05 SL. Results A total of 240 non-squamous pts (Male, 34.6%; East Asian, 55.4%; ECOG PS 0-1, 92.9%) were included. A statistically significant difference in PFS was found across the 3 arms (global p = 0.003), with E + P significantly better than both single agents (HR (95% CI) for E + P vs E was 0.57 (0.40, 0.81), p = 0.002; for E + P vs P was 0.58 (0.39, 0.85), p = 0.005). Median PFS (95% CI) was 7.4 months (4.4, 12.9) in E + P, 3.8 (2.7, 6.3) in E and 4.4 (3.0, 6.0) in P. Safety analyses showed a higher number of pts with ≥1 TEAE with CTCAE grade 3/4 toxicity in E + P (n = 45; 60.0%) than in P (n = 10; 28.9%) or E (n = 22; 12.0%), the majority being neutropenia, anemia, rash and diarrhea. Conclusions Erlotinib + Pemetrexed significantly improved PFS compared to either agent alone in this clinically selected population. E + P had more toxicity, but was clinically manageable. Further analysis of the EGFR mutational status will help to understand and predict which pts will benefit most from this approach. Disclosure X. Wang: I am employee of Eli Lilly and Company. S. Altug: I am employee of, and hold stock/stock options in, Eli Lilly and Company. M. Orlando: “I am employed by and hold stock in Eli Lilly & Company”. All other authors have declared no conflicts of interest.