First-line Use Research Articles

Influence of factor 5 rs6025 and factor 2 rs1799963 mutation on inhibitor development in patients with hemophilia A - an Israeli-German multicenter database study

The present cohort study was performed to investigate the impact of the factor 5 rs6025 [F5] and the factor 2 rs1799963 [F2] mutations on high-titer inhibitor development [HRI] in patients with severe/moderate-severe hemophilia A [HA]. 216 patients with F8<2% born between 1980 and 2011 were followed after initial HA diagnosis over the first 200 exposure days. The first HA patient per family who presented for diagnosis was included in the present study. 32 of 216 children [14.8%] tested for F5/F2 carried either the F5 or the F2 variant. HRI occurred in 14 out of 32F5/F2-carriers compared with 40 of 184 without F5/F2. Multivariate analysis adjusted for F8 genotype, treatment intensity, first-line use of plasma derived FVIII versus recombinant FVIII concentrates revealed that the presence of F5/F2 independently increases the risk of HRI development to odds [OR] of 3.4. Large deletions in the F8 gene [OR: 5.10], patients from Israel [OR: 4.0], the increase of FVIII per one IU/kgbw [OR: 1.05] and birth year [OR: 1.12] were significantly associated with the risk to develop HRI. Data presented here suggest that HRI development is of multifactorial origin and that F5 and F2 mutations may contribute to this risk.

Antenatal atazanavir: a retrospective analysis of pregnancies exposed to atazanavir.

Introduction. There are few data regarding the tolerability, safety, or efficacy of antenatal atazanavir. We report our clinical experience of atazanavir use in pregnancy. Methods. A retrospective medical records review of atazanavir-exposed pregnancies in 12 London centres between 2004 and 2010. Results. There were 145 pregnancies in 135 women: 89 conceived whilst taking atazanavir-based combination antiretroviral therapy (cART), “preconception” atazanavir exposure; 27 started atazanavir-based cART as “first-line” during the pregnancy; and 29 “switched” to an atazanavir-based regimen from another cART regimen during pregnancy. Gastrointestinal intolerance requiring atazanavir cessation occurred in five pregnancies. Self-limiting, new-onset transaminitis was most common in first-line use, occurring in 11.0%. Atazanavir was commenced in five switch pregnancies in the presence of transaminitis, two of which discontinued atazanavir with persistent transaminitis. HIV-VL < 50 copies/mL was achieved in 89.3% preconception, 56.5% first-line, and 72.0% switch exposures. Singleton preterm delivery (<37 weeks) occurred in 11.7% preconception, 9.1% first-line, and 7.7% switch exposures. Four infants required phototherapy. There was one mother-to-child transmission in a poorly adherent woman. Conclusions. These data suggest that atazanavir is well tolerated and can be safely prescribed as a component of combination antiretroviral therapy in pregnancy.

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First-line natalizumab in multiple sclerosis: rationale, patient selection, benefits and risks

Natalizumab (NTZ) is a highly effective disease modifying therapy for the treatment of relapsing forms of multiple sclerosis (MS). Despite evidence to support its use as first-line therapy, risk of NTZ-associated progressive multifocal leukoencephalopathy (PML) has largely contributed to it being relegated to a second-line position. Recent preliminary data may allow for a more accurate analysis of JC virus (JCV) risk stratification of a given patient's PML risk. Herein we propose an algorithm to help guide clinicians through this decision-making process. We recommend that NTZ be considered for first-line use in JCV antibody negative MS patients, JCV 'low positive' MS patients without prior exposure to immunosuppression and for a limited period (12-24 months) in JCV 'high positive' MS patients with an aggressive disease course . We caution against first-line use in JCV antibody 'high positive' patients beyond 12-24 months and any JCV antibody positive patient with a history of prior immunosuppression.

Temporal Trends in the Characteristics of Children at Antiretroviral Therapy Initiation in Southern Africa: The IeDEA-SA Collaboration

BackgroundSince 2005, increasing numbers of children have started antiretroviral therapy (ART) in sub-Saharan Africa and, in recent years, WHO and country treatment guidelines have recommended ART initiation for all infants and very young children, and at higher CD4 thresholds for older children. We examined temporal changes in patient and regimen characteristics at ART start using data from 12 cohorts in 4 countries participating in the IeDEA-SA collaboration.Methodology/Principal FindingsData from 30,300 ART-naïve children aged <16 years at ART initiation who started therapy between 2005 and 2010 were analysed. We examined changes in median values for continuous variables using the Cuzick's test for trend over time. We also examined changes in the proportions of patients with particular disease severity characteristics (expressed as a binary variable e.g. WHO Stage III/IV vs I/II) using logistic regression. Between 2005 and 2010 the number of children starting ART each year increased and median age declined from 63 months (2006) to 56 months (2010). Both the proportion of children <1 year and ≥10 years of age increased from 12 to 19% and 18 to 22% respectively. Children had less severe disease at ART initiation in later years with significant declines in the percentage with severe immunosuppression (81 to 63%), WHO Stage III/IV disease (75 to 62%), severe anemia (12 to 7%) and weight-for-age z-score<−3 (31 to 28%). Similar results were seen when restricting to infants with significant declines in the proportion with severe immunodeficiency (98 to 82%) and Stage III/IV disease (81 to 63%). First-line regimen use followed country guidelines.Conclusions/SignificanceBetween 2005 and 2010 increasing numbers of children have initiated ART with a decline in disease severity at start of therapy. However, even in 2010, a substantial number of infants and children started ART with advanced disease. These results highlight the importance of efforts to improve access to HIV diagnostic testing and ART in children.

Palliative Treatment of Metastatic Colorectal Cancer: What is the Optimal Approach?

Worldwide, colorectal cancer (CRC) is responsible for over 600,000 deaths annually and remains a significant public health concern. Because of therapeutic advancements over the past two decades, patients with metastatic CRC are living longer with an improved quality of life. This review will highlight recent trial evidence that improves outcomes for patients with metastatic disease. Topics will include the optimal use of first-line combination chemotherapy, bevacizumab in patients with advanced age or comorbidities, maintenance chemotherapy, first-line use of anti-EGFR therapies, first-line cetuximab versus bevacizumab, anti-angiogenic therapies past progression, and management of treatment-refractory disease. Clinical trial evidence will be presented, along with guidance on how to integrate recent evidence into clinical practice. Finally, this review will examine innovative drug development strategies, and will discuss potentially actionable targets identified by molecular testing.

Crizotinib: A Review of Its Use in the Treatment of Anaplastic Lymphoma Kinase-Positive, Advanced Non-Small Cell Lung Cancer

Crizotinib (Xalkori(®)) is an orally active, small molecule inhibitor of multiple receptor tyrosine kinases, including anaplastic lymphoma kinase (ALK), c-Met/hepatocyte growth factor receptor and c-ros oncogene 1. In the EU, crizotinib has been conditionally approved for the treatment of adults with previously treated, ALK-positive, advanced non-small cell lung cancer (NSCLC). This approval has been based on objective response rate and tolerability data from two ongoing phase I/II studies (PROFILE 1001 and PROFILE 1005); these results have been substantiated and extended by findings from an ongoing phase III study (PROFILE 1007) in patients with ALK-positive, advanced NSCLC who had received one prior platinum-based regimen. Those treated with crizotinib experienced significant improvements in progression-free survival, objective response rate, lung cancer symptoms and global quality of life, as compared with those treated with standard second-line chemotherapy (pemetrexed or docetaxel). The relative survival benefit with crizotinib is unclear, however, as the data are still immature and likely to be confounded by the high cross-over rate among chemotherapy recipients. Crizotinib treatment was generally well tolerated in the three PROFILE studies, with liver transaminase elevations and neutropenia being the most common grade 3 or 4 adverse events. Crizotinib is the standard of care in terms of the treatment of patients with ALK-positive, advanced NSCLC; while the current EU approval is for second (or subsequent)-line use only, the first-line use of the drug is being evaluated in ongoing phase III studies. Key issues relating to the use of crizotinib in clinical practice include identifying the small subset of eligible patients, the almost inevitable development of resistance and the high cost of treatment.

Chemoimmunotherapy With Fludarabine (F), Cyclophosphamide (C), and Rituximab (R) (FCR) Versus Bendamustine and Rituximab (BR) In Previously Untreated and Physically Fit Patients (pts) With Advanced Chronic Lymphocytic Leukemia (CLL): Results Of a Planned Interim Analysis Of The CLL10 Trial, An International, Randomized Study Of The German CLL Study Group (GCLLSG)

Chemoimmunotherapy With Fludarabine (F), Cyclophosphamide (C), and Rituximab (R) (FCR) Versus Bendamustine and Rituximab (BR) In Previously Untreated and Physically Fit Patients (pts) With Advanced Chronic Lymphocytic Leukemia (CLL): Results Of a Planned Interim Analysis Of The CLL10 Trial, An International, Randomized Study Of The German CLL Study Group (GCLLSG)

Off-Label Topical Calcineurin Inhibitor Use in Children

To assess off-label use of the topical calcineurin inhibitors (TCIs), tacrolimus and pimecrolimus, in children during periods before and after regulatory action by the US Food and Drug Administration (FDA) in 2005. We identified new pediatric (age <20 years) users of topical tacrolimus or pimecrolimus in US Medicaid from 2001 to 2009, and examined the annual rate of drug use (pre- and postregulatory action) by age. We assessed medical claims for diagnoses consistent with an indication for a TCI, and assessed prescriptions for evidence of first-line atopic dermatitis therapy use before TCI initiation. There were 57,664 eligible pediatric tacrolimus users and 425,242 eligible pediatric pimecrolimus users at baseline. The rate of TCI use decreased substantially after FDA regulatory action. The proportion of new users younger than 2 years of age significantly decreased for both tacrolimus (36.7% to 22.5%, P < .001) and pimecrolimus (47.0% to 33.7%, P < .001) after regulatory actions. Previous use of topical corticosteroids increased by ≈ 7% for both TCIs from the pre- to postregulatory period. However, after regulatory actions, there was only a small increase in the proportion of tacrolimus or pimecrolimus users with an atopic dermatitis or eczema diagnosis before drug initiation, and high strength use of tacrolimus was unchanged. The rate of TCI use in children younger than 2 years of age fell substantially after FDA regulatory action in 2005. Off-label use of TCI as first-line therapy changed little.

Sunitinib as First-Line Neoadjuvant Therapy in Two Patients with Rectal Stromal Tumors

In the treatment of rectal stromal tumors, which account for approximately 5% of gastrointestinal stromal tumors, molecular-targeted neoadjuvant therapy should be considered if the tumor is too large to achieve R0 grade resection or multiple visceral resection is required. Currently, imatinib is generally recommended as the first-line agent for such therapy. Although it has been reported that neoadjuvant therapy in patients experiencing imatinib resistance or intolerable adverse events can be successfully achieved by switching to sunitinib, first-line use of sunitinib for neoadjuvant therapy of gastrointestinal stromal tumors has not previously been reported. In this case report, first-line sunitinib neoadjuvant therapy of two patients who had very large rectal stromal tumors at sites close to the prostate and bladder produced good clinical outcomes.

Cost-effectiveness analysis of solifenacin versus oxybutynin immediate-release in the treatment of patients with overactive bladder in the United Kingdom

Objective:To carry out a cost-utility analysis comparing initial treatment with solifenacin 5 mg/day vs oxybutynin immediate-release (IR) 15 mg/day for the treatment of patients with overactive bladder (OAB) from the perspective of the UK National Health Service (NHS).Methods:A Markov model with six health states was developed to follow a cohort of OAB patients treated with either solifenacin or oxybutynin during a 1-year period. Costs and utilities were accumulated as patients transited through the health states in the model and a drop-out state. Some of the solifenacin patients were titrated from 5 mg to 10 mg/day at 8 weeks. A proportion of drop-out patients were assumed to continue treatment with tolterodine ER. Utility values were obtained from a Swedish study and pad use was based on a multinational clinical trial. Adherence rates for individual treatments were derived from a UK database study. For pad use and utility values, the drop-out state was split between those patients who were no longer receiving treatment and those on second-line therapy. Patients on second-line therapy who drop-out were referred for a specialist visit. Results were expressed in terms of incremental cost-utility ratios.Results:Total annual costs for solifenacin and oxybutynin were £504.30 and £364.19, respectively. First-line drug use represents 49% and 4% of costs and pad use represent 23% and 40% of costs for solifenacin and oxybutynin, respectively. Differences between cumulative utilities were small but were greater for solifenacin (0.7020 vs 0.6907). The baseline incremental cost-effectiveness ratio was £12,309/QALY.Conclusion:Under the baseline assumptions, solifenacin would appear to be cost-effective with an incremental cost-utility of less than £20,000/QALY. However, small differences in utility between the alternatives and the large number of drop-outs means that the results are sensitive to small adjustments in the values of utilities assigned to the drop-out state.

Dipeptidyl peptidase-4 inhibitors in type 2 diabetes therapy--focus on alogliptin.

Type 2 diabetes mellitus is a complex and progressive disease that is showing an apparently unstoppable increase worldwide. Although there is general agreement on the first-line use of metformin in most patients with type 2 diabetes, the ideal drug sequence after metformin failure is an area of increasing uncertainty. New treatment strategies target pancreatic islet dysfunction, in particular gut-derived incretin hormones. Inhibition of the enzyme dipeptidyl peptidase-4 (DPP-4) slows degradation of endogenous glucagon-like peptide-1 (GLP-1) and thereby enhances and prolongs the action of the endogenous incretin hormones. The five available DPP-4 inhibitors, also known as ‘gliptins’ (sitagliptin, vildagliptin, saxagliptin, linagliptin, alogliptin), are small molecules used orally with similar overall clinical efficacy and safety profiles in patients with type 2 diabetes. The main differences between the five gliptins on the market include: potency, target selectivity, oral bioavailability, long or short half-life, high or low binding to plasma proteins, metabolism, presence of active or inactive metabolites, excretion routes, dosage adjustment for renal and liver insufficiency, and potential drug–drug interactions. On average, treatment with gliptins is expected to produce a mean glycated hemoglobin (HbA1c) decrease of 0.5%–0.8%, with about 40% of diabetic subjects at target for the HbA1c goal <7%. There are very few studies comparing DPP-4 inhibitors. Alogliptin as monotherapy or added to metformin, pioglitazone, glibenclamide, voglibose, or insulin therapy significantly improves glycemic control compared with placebo in adult or elderly patients with inadequately controlled type 2 diabetes. In the EXAMINE trial, alogliptin is being compared with placebo on cardiovascular outcomes in approximately 5,400 patients with type 2 diabetes. In clinical studies, DPP-4 inhibitors were generally safe and well tolerated. However, there are limited data on their tolerability, due to their relatively recent marketing approval. Alogliptin will be used most when avoidance of hypoglycemic events is paramount, such as in patients with congestive heart failure, renal failure, and liver disease, and in the elderly.

A fixed-dose randomized controlled trial of olanzapine for psychosis in Parkinson disease

Background: Psychosis is a common and debilitating side effect of long-term dopaminergic treatment of Parkinson disease (PD). While clozapine is an effective treatment, the need for blood monitoring has limited its first-line use. Objective: Since olanzapine shows similar receptor affinity to clozapine, we hypothesized that it might be an effective alternative to clozapine for treatment of drug-induced psychosis (DIP) in PD, and that lower doses than usual might make it tolerable. Methods: In 1998-2003 we conducted a four-week, double-blind, placebo-controlled, parallel group, fixed-dose trial of olanzapine (0, 2.5mg, or 5mg) in 23 PD patients with DIP while allowing for clinically realistic dose adjustments of dopaminomimetic mid-study. The primary outcome measures were Brief Psychiatric Rating Scale (BPRS) ratings scored from videotaped interviews after study termination by an observer blinded to dose assignment and to interview timing, and CGI (Clinical Global Impression). The Unified Parkinson’s Disease Rating Scale motor subscale (UPDRS) was the primary measure of tolerability. Results: Intention-to-treat analysis found no significant differences among treatment groups in study completion or serious adverse events. However, a disproportionate number of olanzapine vs. placebo subjects reported mild side effects (p<0.04), many citing motor worsening. Fourteen patients completed the study (seven on placebo, two on 2.5mg olanzapine, five on 5mg olanzapine). In study completers, analysis by repeated measures ANOVA revealed no significant difference between olanzapine and placebo groups in BPRS psychosis reduction (p=0.536), parkinsonism (p=0.608), or any other measured parameters (CGI, MMSE, Beck Depression Inventory, Hamilton Depression score, PDQ‑39, Schwab-England ADL assessment, and sleep scores). Conclusion: This study adds to other evidence that olanzapine is ineffective in treating medication-induced psychosis in Parkinson disease.

Resistance at Virological Failure Using Boosted Protease Inhibitors Versus Nonnucleoside Reverse Transcriptase Inhibitors As First-Line Antiretroviral Therapy—Implications for Sustained Efficacy of ART in Resource-Limited Settings

Increases in the prevalence of resistance to nonnucleoside reverse transcriptase inhibitors (NNRTIs) have been observed among previously untreated individuals in all areas of sub-Saharan Africa. We aimed to examine whether first-line use of 2 NRTIs plus a boosted protease inhibitor (bPI) could protect against emergence of NRTI resistance mutations, compared to the use of 2 NRTIs plus 1 NNRTI. We carried out a weighted meta-analysis of randomized clinical trials comparing bPI- with NNRTI-based first-line antiretroviral therapy regimens using random effects modeling. In intention to treat analyses, there was no difference in the risk of viral failure at week 48 between NNRTI and bPI (P = .19). At week 48, the overall difference between NNRTI- and PI-based regimens in selection of any major NRTI resistance mutation (crude unweighted prevalence 3.3% vs 1.6%) was 1.7% (95% confidence interval [CI], .4-3.0; P = .00927). There was a statistically significant difference in prevalence of K65R when comparing NNRTI (1.3%) with PI (0.67%); absolute weighted difference 1.0% (95% CI, .3-1.7; P = .00447). There was also a significant difference in prevalence of M184V/I between NNRTI and PI (crude unweighted prevalence 3.2% vs 1.4%); difference 1.6% (95% CI 0.1-3.1; P = .0368). Despite the equivalent efficacy and more favorable resistance implications of PI- versus NNRTI-based first line therapy, widespread use of PI-based first-line therapy is not warranted at this time, due to resource limitations and predicted increased risk of resistance-related failure of NNRTI/NRTI second-line regimens. PI-based first-line therapy could be reconsidered when antiretroviral agents from other classes become available for second-line regimens in resource-limited settings.

Superselective renal artery embolization in the treatment of renal hemorrhage

Renal hemorrhage is a potentially life-threatening event that may follow trauma, operation, biopsy, and sudden spontaneous rupture of renal tumors or aneurysms. Superselective renal artery embolization (SRAE) is a well-established method for such cases. To assess the effectiveness of SRAE in the treatment of renal hemorrhage at our institute. We respectively reviewed the medical records of patients who underwent SRAE for renal hemorrhage from January 2005 to June 2012. Data on patients' characteristics, indications, requirement of pre-embolization blood transfusion, angiographic finding, location of bleeding site, embolization agents, post-embolization transfusion requirement, complications and the outcome were recorded. A total of 46 patients, aged 26-73 years, underwent SRAE because of hemorrhage after percutaneous nephrolithotomy (n = 25), partial nephrectomy (n = 6), renal biopsy (n = 2), trauma (n = 2), rupture of angiomyolipoma (n = 4), renal aneurysm (n = 1), and renal ateriovenous malformations (n = 6). A total of 41 patients (80.8 %) underwent successful embolization. Treatment failed in 5 patients with hemorrhage caused by percutaneous nephrolithotomy. Of these, four patients underwent a secondly superselective embolization and had a successful outcome. The remaining one was managed by conservative therapy with repeated blood transfusions. No patient required nephrectomy to save the life of the patient. No serious procedure-related complications occurred. SRAE is an effective and minimal invasive method for the control of renal hemorrhage. Our experience strongly recommended the first-line use of SRAE for severe renal hemorrhage.

Fludarabine in Waldenstrom’s macroglobulinemia

Waldenstrom’s macroglobulinemia is a rare chronic lymphoproliferative disorder. Treatment is usually based on nucleoside analogues, alkylators, bortezomib and monoclonal antibodies, alone or in combination. Fludarabine is a fluorinated purine analogue effective in chronic lymphoproliferative disorders. In Waldenstrom’s macroglobulinemia, fludarabine was first studied in patients with relapsed or refractory disease after alkylator therapy, yielding an overall response rate of 30%. In the late 1990s, fludarabine started to be used as a first-line treatment monotherapy yielding response rates between 36 and 94%. A recent Phase III trial showed that fludarabine monotherapy was more effective than chlorambucil in terms of progression-free survival, duration of response and overall survival. Fludarabine has also been studied in combination with rituximab and/or alkylating agents, leading to better-quality and longer lasting responses. Hematological toxicity is a major concern; however, restricting first-line use of fludarabine in patients who do not qualify for autologous stem cell transplantation, require rapid disease control or have factors of poor prognosis.

Trends in selection and timing of first‐line pharmacotherapy in older patients with Type 2 diabetes diagnosed between 1994 and 2006

To characterize temporal trends in the selection and timing of first-line pharmacotherapy among older patients with Type 2 diabetes. We studied five population-based cohorts every 3 years, from 1994 to 2006. In each of those years, we identified all subjects aged 66 years or older newly diagnosed with diabetes and determined the initial glucose-lowering drug and the time between diagnosis and drug initiation. We calculated the proportion of patients prescribed each agent and estimated time from diagnosis to initiation using Kaplan-Meier survival analysis. We identified a total of 64 368 eligible people who initiated drug therapy during the study period. From 1994 to 2006, first-line metformin use increased from 20.1 to 79.0%. Glyburide (glibenclamide) decreased from 71.1% of all first-line therapies in 1994 to 9.8% in 2006, while first-line use of insulin or combination therapy have changed little at approximately 5% each. No other medication exceeded 2% of first-line therapies. The median time from diagnosis to initiation of pharmacotherapy increased dramatically during the study period, from 1.8 years in 1994 to 4.6 years in 2006. Metformin has become the most commonly used initial medication for the treatment of diabetes. Although guidelines have evolved to recommend more aggressive initiation and intensification of pharmacotherapy, our results suggest that the time from diagnosis to initiation has increased substantially.

Is erlotinib for first-line use in EGFR+ non-small-cell lung cancer cost-effective?

e19001 Background: A recent phase III clinical trial, EURTAC, demonstrated that first-line treatment with erlotinib significantly improved progression-free survival (PFS) compared with standard chemotherapy in advanced non-small cell lung cancer (NSCLC) patients whose tumors harbored epidermal growth factor receptor (EGFR) mutations (Rosell 2012). We sought to estimate the cost-utility of treatment with erlotinib in this patient population from the US payer perspective. Methods: We developed a Markov model with three health states: PFS, progression, and death. Patients received treatment until progression, unacceptable toxicity or death; patients randomized to chemotherapy received a maximum of 4 treatment cycles. Transition probabilities were extrapolated from the trial. Median PFS was 9.7 months in patients receiving erlotinib and 5.2 months in patients receiving chemotherapy (p&lt;0.0001). Cost and utility data were obtained from the literature. Probabilistic sensitivity analysis (PSA) was performed to assess uncertainty. We evaluated two scenarios: 1) first-line erlotinib vs. first-line chemotherapy, and 2) first-line erlotinib and mixed second-line treatments vs. first-line chemotherapy and second-line erlotinib. Results: First-line treatment with erlotinib vs. chemotherapy resulted in an increase of 0.60 life-years or 0.44 quality-adjusted life-years (QALYs). Mean total costs were $59,300 in the erlotinib arm and $17,800 in the chemotherapy arm, yielding an incremental cost-effectiveness ratio (ICER) of $98,338 with a 53% probability of being cost-effective at a willingness to pay (WTP) of $100,000/QALY. In the second scenario, the ICER was $50,002/QALY, with a 66% probability of being cost-effective. The main cost drivers in the model were the time spent in the PFS health state and drug costs. Conclusions: Treatment with erlotinib in first-line EGFR-positive NSCLC results in increased costs but also substantial increases in QALYs, demonstrating that this personalized approached to treatment may be cost-effective.

A survey on Japanese thoracic oncologists’ preference on treatment strategy for EGFR-mutant or EML4-ALK-mutant non-small cell lung cancer (NSCLC).

e19124 Background: NSCLC pts have become categorized based on two genetic alterations in their tumors, EGFR and EML4-ALK, to provide personalized therapy. In EGFR-mutant NSCLC, EGFR-TKI yields a comparable survival with platinum-based chemotherapy, suggesting either of them can be initiated first, and its choice seems to depend partly on oncologists’ preference. As for the other, EML4-ALK, NCCN guideline recommends first-line crizotinib use despite no relevant survival data. The decision whether to choose crizotinib might be also influenced by oncologists’ preference. We here assessed their preference. Methods: The Japanese thoracic oncologists were asked to complete a self-administered questionnaire at the Japanese meeting specific for thoracic oncology. Results: Of 3,046 subjects, 871 (29%) responded voluntarily to a survey, mainly consisting of medical and surgical oncologists (93%). Majority considered EGFR mutation status should be checked at the time of diagnosis (89%), whereas only 60% and 33% reported EML4-ALK gene status would be assessed at the time of diagnosis and until the initiation of second-line setting, respectively. The subjects also considered pts with EGFR-wild-typed tumor and pts with clinical characteristics possibly related to EML4-ALK rearrangement should selectively receive EML4-ALK gene status check rather than all NSCLC pts (57%, 22% and 16%, respectively). Among the subjects, 52% preferred to choose gefitinib rather than platinum in the first-line setting in EGFR-mutant NSCLC, whilst 44% preferred crizotinib to platinum in the first-line setting in EML4-ALK-positive NSCLC. The major reasons why they chose gefitinib in EGFR-mutant NSCLC were ‘PFS is better’ (36%) and ‘it is easy to improve QOL’ (25%), whereas ‘PFS is better’ (43%), and ‘I want to prescribe when patients are still in good condition’ (19%) were the predominant reasons for choosing crizotinib in EML4-ALK-positive NSCLC. Conclusions: About half of the subjects preferred each molecular-targeted agent to the conventional cytotoxic chemotherapy in first-line setting. They considered better PFS was important in the treatment of EGFR-mutant or EML4-ALK-mutant NSCLC.

PSY38 - First-line use of calcipotriene/betamethasone dipropionate combination products for the treatment of plaque psoriasis is associated with lower health care utilization and cost

PSY38 - First-line use of calcipotriene/betamethasone dipropionate combination products for the treatment of plaque psoriasis is associated with lower health care utilization and cost