Payment For Lectures Research Articles

424.9: Real-World Treatment Patterns and Outcomes For Cytomegalovirus Infection and Disease in Hematopoietic Stem Cell Transplant Recipients in Selected Countries Outside of North America and Europe: A Systematic Review

Background: There is a paucity of real-world data on treatments used for cytomegalovirus (CMV) in hematopoietic stem cell transplant (HSCT) recipients, which differ across countries, outside of developed markets. To address this knowledge gap, a systematic review was conducted to evaluate current treatment patterns for CMV infection and disease following HSCT in selected countries outside of North America and Europe and describe related outcomes. Methods: Information sources (search period: 01 Jan. 2011 – 21 Jul. 2021) included indexed literature (Ovid® MEDLINE and Embase, Cochrane Database of Systematic Reviews and World Health Organization database Global Index Medicus), conference abstracts, pragmatic searches of the grey literature and snowballing of references lists of retained studies. Observational studies of interest included HSCT recipients (any age) who developed CMV infection or disease in 15 selected countries in Asia-Pacific, Latin America, Russia, and the Middle East. Outcomes of interest were treatment patterns for CMV infection and CMV disease, proportion of patients (pts) with resistant and refractory CMV including definitions, treatment-related outcomes and adverse events (AEs). The protocol was registered in PROSPERO (CRD42020205559). Results: Out of 25 retained studies (33 to 475 pts), most included allogeneic HSCT recipients (n=21, 84.0%) and adult pts (n=20, 80.0%). In HSCT recipients, pre-emptive therapy with intravenous ganciclovir (IV GCV) and/or valganciclovir (VGCV) is the conventional first-line (1L) approach for CMV infection prevention, with a median treatment duration of 14-24 days (5 studies). GCV IV was also the conventional treatment for CMV disease (5 studies), with treatment lasting 12-30 days (3 studies). Neutropenia was observed in 30.0% and 39.8% pts treated with GCV and, in 3 studies, neutropenia, myelosuppression, and nephrotoxicity led to GCV discontinuation, respectively, in 13.6%, 10.0%, and 2.3% of pts. In 3 studies, up to 10.0% of pts had second-line (2L) treatment with foscarnet, due to GCV-related myelosuppression. The reported proportion of pts with resistant CMV (definition not specified) ranged between 0% and 7.7% (5 studies; Figure 1). These pts received foscarnet or cidofovir as 2L therapy for a mean duration of 14 days (no data on AEs reported). In 3 studies, estimates of refractory CMV were 2.9%, 13.0%, and 49.4% (latter estimate reported in 39 pts, of whom 56.0% had recurrent CMV). Conclusion: In selected countries outside of North America and Europe, conventional therapeutic options for pre-emptive and treatment of CMV infection and CMV disease following HSCT were IV GCV and VGCV. However, premature treatment discontinuation occurred in up to 1 in 8 pts, highlighting an unmet need with current standard of care. Real-world outcomes in pts with refractory CMV (with or without resistance) were scarce and warrants further investigation in this patient population, including therapeutic management.This review was funded by Takeda International AG – Singapore Branch. S-YC has served as a consultant for Takeda Pharmaceutical, and has received research support and payment for lectures from Merck Sharp & Dohme, Pfizer and Gilead. WD has no conflicts of interest to disclose. CMM has received honoraria from Takeda and MSD (advisory board, speaker, educational events, meetings). IS is an employee of Takeda Pharmaceuticals India Pvt Ltd. AS and DD are employees of Takeda International AG – Singapore Branch and hold stock options. MS has received grants from F2G, Gilead, Merck and personal fees from Gilead, Pfizer, Takeda and Roche for work outside of this research. Literature retrieval, analysis and medical writing support were provided by Aurore Bergamasco, Camille Goyer, and Yola Moride of Yolarx Consultants and funded by Takeda International AG – Singapore Branch.

424.1: Epidemiology of Cytomegalovirus Infection and Disease in Hematopoietic Stem Cell Transplant Recipients in Selected Countries Outside of North America and Europe: A Systematic Review

Background: Cytomegalovirus (CMV) is a highly prevalent herpes virus with a seroprevalence higher in South America, Africa, and Asia than in Europe and North America. In hematopoietic stem cell transplant recipients (HSCT), CMV infection is a common opportunistic infection and a major cause of morbidity and mortality. To better understand the epidemiology of CMV infection and disease post-HSCT in selected countries outside of Europe and North America, a systematic review was conducted. Methods: Observational studies that included HSCT recipients (any age) from 15 selected countries in Asia-Pacific, Latin America, Russia and the Middle East were considered (search period: 01 Jan. 2011 – 21 Jul. 2021). Outcomes of interest were incidence, recurrence rates and risk factors of CMV infection and CMV disease, and CMV-related mortality at any time point. Indexed publications (Ovid® MEDLINE and Embase, Cochrane Database of Systematic Reviews and World Health Organization database Global Index Medicus) were searched, supplemented by pragmatic searches of the grey literature and snowballing of references lists. The protocol was registered in PROSPERO (CRD42020205559). Results: A total of 63 studies (range: 33 to 10,206 patients), most conducted in adults (≥ 18 years; n=49 studies, 77.8%) and allogeneic HSCT recipients (n=53, 84.1%), were included in the review. In 43 of 54 studies reporting on incidence of CMV infection, within 1 year post-HSCT, estimates were uniformly distributed between 24.8% and 61.2% (Figure 1). Lower estimates were reported in autologous HSCT recipients (5.3%), and younger patients at the time of transplantation (9.3% in adults with a median age of 25 years and 18.6% in patients aged ≤20 years). Higher estimates (range: 69.4% to 88.2%) were found in 8 studies from China and South Korea, most with a follow-up period > 1 year (median: 27 to 54 months in 5 studies) (Figure 2). Incidence of CMV disease following HSCT was below 20%, with estimates uniformly distributed between 0% and 15.7% in allogeneic HSCT. According to 11 studies, reported rates of CMV recurrence ranged between 19.8% and 37.9%. Commonly reported risk factors for CMV infection or disease in HSCT recipients were high-risk CMV serostatus (R+) (hazard ratio [HR]: 2.6 and 3.7, odds ratio [OR]: 2.2 and 5.4), older age of recipients (HR for each additional year: 1.03-1.04), presence of acute or chronic graft versus host disease (HR: 1.1-2.5), haploidentical HSCT (HR: 2.7-6.4), and use of immunosuppressive agents (OR: 5.0-9.3). CMV-related mortality was reported in up to 10% of patients following HSCT (n=30 studies; period of assessment not reported). Conclusion: Relatively high rates of CMV infection, CMV disease and CMV recurrence were reported post-HSCT, with CMV-related mortality observed in up to 1 in every 10 patients. High rates of CMV infection and disease post-HSCT may impact graft outcomes and increase disease burden in patients post-transplantation.This review was funded by Takeda International AG – Singapore Branch. CMM has received honoraria from Takeda and MSD (advisory board, speaker, educational events, meeting). S-YC has served as a consultant for Takeda Pharmaceutical, and has received research support and payment for lectures from Merck Sharp & Dohme, Pfizer and Gilead. MS has received grants from F2G, Gilead, Merck and personal fees from Gilead, Pfizer, Takeda and Roche for work outside of this research; IS is an employee of Takeda Pharmaceuticals India Pvt Ltd. AS and DD are employees of Takeda International AG – Singapore Branch and hold stock options. WD has no conflicts of interest to disclose. Literature retrieval, analysis and medical writing support were provided by Aurore Bergamasco, Camille Goyer, and Yola Moride of YolaRX Consultants and funded by Takeda International AG – Singapore Branch.

Immunocompromised patients have been neglected in COVID-19 trials: a call for action

Immunocompromised patients have been neglected in COVID-19 trials: a call for action

Invited Commentary: Radiogenomics Applied to Select Abdominal Tumors.

Invited Commentary: Radiogenomics Applied to Select Abdominal Tumors.

Effect of mifepristone on the transcriptomic signature of endometrial receptivity.

How does a single dose of mifepristone on Day 2 after the LH peak (LH + 2) affect the endometrial receptivity transcriptome as assessed by the receptive signature established by the endometrial receptivity analysis (ERA)? A single dose of mifepristone on day LH + 2 renders the endometrium non-receptive by altering the transcriptome associated with endometrial receptivity. Mifepristone is a progesterone receptor modulator that has been shown to alter endometrial receptivity. The ERA is a computational predictor that utilizes gene expression data of 248 genes from next generation sequencing to identify endometrial receptivity status. Endometrial biopsies were collected on day LH + 7 from controls (n = 11) and from women treated with mifepristone (n = 7). For further comparative analysis, samples were also obtained from women in the proliferative phase (n = 7). Mifepristone treatment consisted of 200 mg administered on day LH + 2. Endometrial biopsies were treated for RNA isolation and cDNA conversion and sequencing. Endometrial receptivity status was assessed by the ERA computational predictor. Differential gene expression between groups was also assessed. Ingenuity Pathway Analysis was used for network analysis. Validation of gene expression results was done by qPCR. Control samples were all staged around 'receptive' as would be clinically expected for LH + 7. Treatment samples were all staged as non-receptive (all but one was classified as 'proliferative' and the last as 'pre-receptive'). Differential gene expression analysis yielded 60 differentially expressed genes between the control and treatment groups. Bioinformatic pathway analysis for differential expression showed inactivation of the progesterone and glucocorticoid receptors, consistent with mifepristone action. The primary limitations are the relative small number of subjects and the use of a limited gene panel. This study sheds further light on the endometrial receptivity altering effects of mifepristone and on progesterone action. It further shows the capacity of the ERA to identify pharmacologically induced non-receptive endometrium, which expands its possible use clinically and in research. C.v.G. and N.R.B. have no conflicts of interest. P.G.L. reports honorarium from University of HK/Shenzhen, other from NIF, India, outside the submitted work. K.G.D. reports consultancy for Bayer AG, Exelgyn, HRA-Pharma, Gedeon Richter, MSD, Mithra, Exeltis and Natural cycles, payment for lectures from Bayer AG, NSD, Ferring, HRA-Pharma, Exelgyn and Exeltis and clinical trials for Bayer AG, MSD, Exeltis, Mithra, HRA-Pharma and Sun Pharma. C.S. has a patent gene expression profile (ERA) issued to Igenomix and is scientific director of Igenomix S.L. M.R., R.N. and J.M.V. are employees of Igenomix S.L. N/A.

P11.27 Does accessing non-occupational post exposure prophylaxis and the associated clinical experience impact condom use among men who have sex with men in victoria, australia

Background Condom promotion is a key component of combination HIV prevention globally. There is evidence from clinical settings that intense interventions successfully increase condom use. However it is unknown if routine sexual health clinical encounters, including encounters potentially prompted by concern relating to particularly high risk events, have the same impact on reducing HIV risk behaviours. We compared self-reported condom use among MSM before and after receiving standard care non-post exposure prophylaxis. Methods Data from MSM accessing the Victorian NPEP Service (VNPEPS) was linked to HIV/STI testing data from Victorian Primary Care Network for sentinel surveillance (VPCNSS) clinics between 2007–2013. Analysis included data from MSM who accessed NPEP and reported condom use at their most recent HIV/STI test prior to NPEP (baseline) and two tests following NPEP (follow-up one and two). Only the first NPEP episode was included. Proportion of MSM reporting inconsistent condom use at baseline (test immediately prior to NPEP) and follow-up one and two were compared using a two sample test of proportions. Results Among 1199 MSM presenting for NPEP on 2094 occasions, 6329 test and risk behaviour records were obtained from VPCNSS sites pre-and post-NPEP. A total of 303 MSM had data on condom use at baseline and two follow ups. Inconsistent condom use was reported by 146 (48.2%) of MSM at baseline, 138 (45.5%) at follow-up one (p = 0.60) and 146 (48.2%) at follow-up two (p = 1.0). Follow-up two occurred a median of 15 months (IQR = 10–23) after NPEP presentation. Conclusion In this study we found no change in condom use following NPEP among MSM with pre- and post-NPEP VPCNSS testing histories. Though generalisability to all MSM is limited, this analysis offers insight into a key risk population and highlights the potential need for tailored strategies to promote primary prevention during risk event-prompted clinical presentations. Disclosure of interest statement The Victorian Department of Health funds the VNPEPS and ongoing surveillance projects within the Burnet Institute. The authors would like to acknowledge the NHMRC who provide funding to Margaret Hellard as a Senior Research Fellow, Mark Stoove as a Career Development Fellow and Anna Wilkinson as a public health scholarship recipient. Edwina Wright receives funding from a research grant from NIH, research funding from the Victorian Department of Health and unrestricted research funds from Gilead, Abbott, Janssen Cilag, MSD and Boehringer Ingelheim. She has also received funding that has been used for research purposes only from ViiV, Merck, Gilead, and Abbott for consultancy work, payment for lectures from ViiV and payment for developing educational resources for ViiV, MSD and Gilead. The study drug for the VicPrEP study has been donated by Gilead Sciences. The authors gratefully acknowledge the contribution to this work of Victorian Operational Infrastructure Support Program received by the Burnet Institute.

O19.2 Pre-exposure prophylaxis and risk compensation: evidence of decreased condom use at three-month follow-up among predominantly gay male participants in the vicprep study

Introduction Pre-exposure prophylaxis (PrEP) decreases HIV risk among uninfected people, but risk compensation may affect prevention benefits. PrEP trials and extensions found no decrease in condom use, but included extensive prevention education. We investigated condom use in the VicPrEP study, the first implementation study of PrEP in routine practice in Australia. Methods Enrollment commenced in June 2014, with capacity for 115 at risk HIV negative gay/bisexual men, transgender people and heterosexual serodiscordant couples seeking to conceive. Participants are recruited from three GP clinics, one sexual health clinic, and one hospital clinic in Melbourne. Participants consent to using daily Truvada for at least one year, and complete baseline and three-monthly clinical evaluations and self-report behavioural surveys. Results At 31 March 2015, 92 participants completed baseline surveys, and 76 completed three-month follow-up; all gay/bisexual men (mean age 37.7 years; 67.4% university educated; 75.0% Australian born). In the past three months half had regular partners (Baseline: 48.9%, Follow-up: 55.8%; ns); nearly all had casual partners (Baseline: 90.2%, Follow-up: 88.2%; ns). Mean frequency of intercourse in the past three months remained stable for regular partners (Baseline: 19.0, Follow-up: 18.9; ns), and decreased for casual partners (Baseline: 19.1, Follow-up: 16.0; p = 0.056). Condom use was assessed on a 5-point scale (1 = never, 5 = always), and decreased with regular partners (Baseline: mean 2.0 [SD 1.6], Follow-up: mean 1.7 [SD 1.3]; p = 0.048), and casual partners (Baseline: mean 3.0 [SD 1.3], Follow-up: mean 2.5 [SD 1.4]; p = 0.002). Serosorting, viral load sorting, strategic positioning and withdrawal remained unchanged with regular and casual partners. Conclusion This is the first study documenting a decrease in condom use amongst HIV-negative gay/bisexual men using PrEP. Findings highlight the potential for risk compensation to reduce benefits of PrEP when implemented in routine practice, if adherence is insufficient. This underscores the continued importance of promoting sexual risk reduction practices, including condom use. Disclosure of interest statement The VicPrEP study was funded by the Victorian Department of Health and study drug was supplied by Gilead. John de Wit receives research funding from the National Health and Medical Research Council, the Australian Government Department of Health, the NSW Ministry of Health, the Victorian Department of Health, Queensland Health, Western Australian Department of Health, Gay Men9s Health SA, ACT Health, Tasmanian Council on AIDS, Hepatitis and Related Diseases, the Netherlands Institute of Public Health and Environment (RIVM), AIDS Fonds, The Netherlands, and UNESCO Bangkok. He has received lecture sponsorship from BMS Australia, is a board member of ACON Health Inc and a member of the Steering Committee of the HIV in Europe initiative. Dean Murphy receives funding from the Australian Government Department of Health and a research grant from the Victorian Department of Health. Luxi Lal has no interests to disclose. Jennifer Audsley has no interests to disclose. Norman Roth has received honoraria for Advisory Boards and/or educational events from ViiV, MSD, Gilead and Bristol Myers Squibb. Richard Moore has received financial assistance for education from Gilead, Viiv and Merck. BK Tee has no interests to disclose. Tim Read works at Melbourne Sexual Health Centre which receives study payments from Gilead. Edwina Wright receives funding from a research grant from NIH, research funding from the Victorian Department of Health and unrestricted research funds from Gilead, Abbott, Janssen Cilag, MSD and Boehringer Ingelheim. She has also received funding that has been used for research purposes only from ViiV, Merck, Gilead, and Abbott for consultancy work, payment for lectures from ViiV and payment for developing educational resources for ViiV, MSD and Gilead.

A single-mentor approach to the medical student orthopaedic interest group

Saint Louis University, Department of Orthopaedic Surgery, St. Louis, MO 63110, USA Financial Disclosure: Dr. Cannada has received a grant from Arthrex in the past and payment for lectures from Smith and Nephew. The authors report no financial conflicts of interest. Correspondence to Lisa K. Cannada, MD, Department of Orthopaedic Surgery, Saint Louis University, 3536 Vista Ave, 7th Floor Desloge Tower, Saint Louis, MO 63110 Tel: +314-577-8850; fax: +314-268-5121(f); e-mail: [email protected]

Recovery from Possible Late‐Onset Alzheimer's Dementia? Evidence from a Longitudinal Community‐Based Age‐Cohort Study

Recovery from Possible Late‐Onset <scp>A</scp>lzheimer's <scp>D</scp>ementia? Evidence from a <scp>L</scp>ongitudinal <scp>C</scp>ommunity‐<scp>B</scp>ased <scp>A</scp>ge‐<scp>C</scp>ohort <scp>S</scp>tudy

Is Extracorporeal Cardiopulmonary Resuscitation for Out-of-Hospital Cardiac Arrest Superior Compared With Conventional Resuscitation?*

Division of Cardiothoracic and Vascular Anesthesia and Intensive Care MedicineVienna General HospitalMedical University of ViennaVienna, Austria *See also p. 1186. Dr. Dworschak is a board member of Australian Medical Association (receives refund of expenditures for board exam meetings and payment for lectures). He receives honoraria from Covidien and paid expenses from Covidien.

“All That Glitters is Not Gold…”*

Centre for Clinical Brain Sciences, University of Edinburgh, Western General Hospital, Edinburgh, UK *See also p. 1353. Supported by the National Institute for Health Research Health Technology Assessment (NIHR HTA) Programme, payment for lectures from Integra Neurosciences; travel support to Ru Neuro meeting in Moscow from Integra Neuroscience and support from the University of Chelyabinsk to travel and lecture in the Southern Ural region

Improving the Best Available Evidence Component of Evidence-Based Medicine

*Division of Spine, Department of Orthopaedics, University of British Columbia, Vancouver, British Columbia, Canada; and †Departments of Orthopaedic Surgery and Neurological Surgery, Thomas Jefferson University and The Rothman Institute, Philadelphia, PA. Address correspondence and reprint requests to Alexander R. Vaccaro, MD, PhD, The Rothman Institute, 925 Chestnut Street, Philadelphia, PA 19107. Acknowledgement date: September 18, 2012. Acceptance date: September 22, 2012. The manuscript submitted does not contain information about medical device(s)/drug(s). No funds were received in support of this work. Relevant financial activities outside the submitted work: board membership, consultancy, expert testimony, grants, payment for lectures, patents, royalties, stocks, payment for development of educational presentations.

899PD - Association of Baseline Corticosteroid with Outcomes in a Multivariate Analysis of the Phase 3 Affirm Study of Enzalutamide (ENZA), An Androgen Receptor Signaling Inhibitor (ARSI)

ABSTRACT Background ENZA-proposed INN (MDV3100) increased median survival by 4.8 mo (P Methods Pts were randomized 2:1 to ENZA 160 mg/d or PBO, stratified by baseline ECOG & mean Brief Pain Inventory score (BPI). Efficacy endpoints included Overall Survival (OS), radiographic progression-free survival (rPFS), & time to PSA progression (TTPP). In a post-hoc analysis, pts were evaluated by oral daily CS baseline use. Using a stepwise multivariate Cox proportional-hazards analysis, associations between the OS and the prespecified baseline factors ( treatment [Trt], age, region, ECOG, BPI, visceral disease, number of chemotherapy regimens, progression type at entry, LDH, PSA, hemoglobin, alkaline phosphatase) and CS use were evaluated. Results 800 pts were randomized to ENZA & 399 to PBO. ∼30% of pts in each arm were on CS at baseline. Multivariate analysis showed baseline oral CS use was associated with the OS outcome, with median OS of 11 mo (95% CI: 10, 13) for pts on CS vs median OS not met (18, NM) for pts not on baseline CS (HR = 0.54; 95% CI: 0.45, 0.64)). Subgroup analysis showed for pts on CS median OS was 12.3 mo on ENZA vs 9.3 mo on PBO (P = 0.0116, HR 0.70) and for pts not on CS median was not met on ENZA vs 15.8 mo on PBO (P Results of Stepwise Multivariate Analysis of Overall Survival Variable Parameter Estimates HR for Death (95% CI) Coefficient P-value Treatment (ENZA vs PBO) -0.54 ± 0.090 0.58 (0.49-0.70) Mean pain score: -0.25 ± 0.098 0.0091 0.78 (0.64-0.94) Progression at study entry: PSA only vs radiographic -0.35 ± 0.094 0.0002 0.70 (0.59-0.85) Visceral disease at screening (No vs Yes) -0.42 ± 0.097 0.66 (0.54-0.80) Baseline hemoglobin -0.03 ± 0.003 0.97 (0.97-0.98) Baseline lactate dehydrogenase (LDH) 0.002 ± 0.000 1.002 (1.001-1.002) Baseline corticosteroid use (No vs Yes) -0.62 ± 0.091 0.54 (0.45-0.64) 1. Survival for pts who had not died by the time of analysis was censored at the date the pt was last known to be alive. 2. confidence interval Conclusions Use of CS at baseline was associated with reduced OS in the multivariate model. This finding should be further explored in future studies. While pts on baseline CS had worse outcomes, ENZA was consistently superior to PBO on OS, rPFS, and TTPP regardless of baseline CS use. Disclosure H.I. Scher: Consultant/Advisor Amgen, Aragon, BMS, Dendreon, Exelixis, Foundation, Janssen, J & J, MDV, Millennium, Novartis, Ortho Biotech, Sanofi Aventis. Research support from Aragon, BMS, Exelixis, Medivation, Orthobiotech & Veridex, F. Saad: Grants: Astellas; Consulting fee or honorarium: Astellas, Medivation, Johnson & Johnson; Board membership: Medivation, Astellas, Johnson & Johnson. M. Taplin: Consulting fee or honorarium: Medivation, JNJ, Tokai; Support for travel to meetings for the study or other purposes: Medivation; Travel/accomodations/meeting expenses unrelated to activities listed: JNJ, Tokai. C.N. Sternberg: Consultancy fee or honorarium: Johnson & Johnson, Astellas, Amgen, Sanofi-Aventis. A.J. Armstrong: Consultancy: Amgen, BMS, Sanofi-Aventis; Grants/grants pending: Medivation, Janssen Biotech, Sanofi-Aventis, Imclone, BMS, Pfizer, Novartis, Active Biotech, J & J/Veridex, Dendreon; Payment for lectures: Sanofi-Aventis, Dendreon, Janssen Biotech, Amgen. M. Hirmand: Employement: Medivation; Stock/stock options: Medivation, B. Selby: Employement: Medivation; Stock/stock options: Medivation; Payment for writing or reviewing the manuscript: Medivation; Fees for participation in review activities such as data monitoring boards, statistical analysis, ent point committies, Medivation. J.S. de Bono: Consultancy: Medivation, Astellas. All other authors have declared no conflicts of interest.

Evidence-based Imaging in Lung Cancer

Lung cancer is the leading cause of cancer-related mortality in the United States. To assess prognosis, optimize treatment, and avoid potentially harmful futile treatments it is critical to have a complete understanding of the tumor's histology, molecular characteristics, and stage at the time of diagnosis. From the radiologist's perspective, the goal is to provide as accurate a stage as possible before the use of minimally invasive or invasive procedures to guide the site of biopsy and confirm a final pathologic stage. This article reviews the evidence behind the imaging technologies used in the staging evaluation of lung cancer.

892TiP - Patient Preference for Tivozanib Hydrochloride or Sunitinib in the Treatment of Metastatic Renal Cell Carcinoma (MRCC): Taurus Study

ABSTRACT Purpose Tivozanib hydrochloride is a potent, selective, long half-life inhibitor of vascular endothelial growth factor (VEGF) receptors 1, 2, and 3. Inhibition of VEGF-driven angiogenesis is known to reduce vascularization and tumor growth. Currently, sunitinib is most commonly used as first-line treatment in patients with mRCC. Previous Phase II and Phase III studies have demonstrated the promising efficacy and safety of tivozanib in patients with mRCC. The primary objective of this study is to compare patient preferences for tivozanib or sunitinib. Secondary objectives include assessing overall safety and tolerability, frequency of dose modifications, and quality of life in patients treated with tivozanib and sunitinib.Study design: This Phase II, randomized, double-blind, multinational, crossover study will compare the preference of mRCC patients for tivozanib or sunitinib as treatment for metastatic disease. Recruitment of 160 patients is planned. Patients will be randomized to tivozanib 1.5 mg/d for 12 weeks (wks) (Cycle = 3 wks on, 1 wk off) or sunitinib 50 mg/d for 12 wks (Cycle = 4 wks on, 2 wks off). After a washout period, patients will cross over to the alternate treatment (sunitinib or tivozanib). Methods After 12 wks of treatment, tumor response will be assessed using Response Evaluation Criteria In Solid Tumors (version 1.1). Patients are expected to cross over to the second treatment for 12 wks; however patients with a significant clinical response (defined as >50% tumor reduction or complete response for non-measurable disease) will be given the option to continue the first treatment if they choose. Patients with Grade 3/4 adverse events may have a dose interruption of ≤2 wks to manage toxicities, after which they may continue at the same or reduced dose; dose reductions to 1.0 mg/d for tivozanib and 37.5 mg/d for sunitinib will be allowed. After the second 12-wk period, patients' drug preferences, based on a questionnaire, and their tumor response will be assessed and reviewed prior to a final tumor assessment. Conclusion The double-blind design of this study will enable comprehensive assessment of patient preference for tivozanib and sunitinib as treatment for mRCC. Disclosure B. Escudier: Board Membership:Pfizer, GSK, Bayer, AVEO, Novartis Consultancy: Pfizer, GSK, Bayer, Payment for lectures, service on spkrs bureaus:Pfizer, Novartis Payment for development of educational presentations: Pfizer, GSK, Bayer, AVEO, Novartis. L. Steelman: Current Employment: AVEO with stock options Employment: Novartis until 8/11 Employment: ARIAD until 11/09. D. Cesic: AVEO Pharmaceuticals employee with stock options. A. Berkenblit: AVEO Pharmaceuticals employee with stock options