BACKGROUND: Overweight and obesity are associated with many obesity-related complications (ORCs) and drive increased health care costs. However, data on the impact of obesity severity on multimorbidity and the effect of multimorbidity on cost and health care resource utilization (HCRU) in people with overweight or obesity are limited. OBJECTIVE: To determine in reference to obesity-related multimorbidity (1) if prevalence increases with higher levels of weight class, (2) if higher levels of weight class are associated with an increased risk of multimorbidity at an earlier age, and (3) how HCRU and health care costs are impacted, including if there is a beyond-additive effect on ORC-related costs. METHODS: This retrospective cross-sectional study used linked electronic health records (EHRs) and insurance claims from Optum's de-identified Market Clarity Data. Costs were considered from January 1 to December 31, 2019. Patients continuously insured in 2018 and 2019 with at least 1 recorded body mass index (BMI) in 2019 were included. The presence of 17 prespecified ORCs was determined from the database based on the International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) diagnosis codes. ORC-related medical services costs were based on ICD-10-CM diagnosis codes in the primary position; pharmacy costs were based on National Drug Codes. Total health care costs were the sum of medical services and pharmacy costs. Weight classes were derived from the patients' median BMI in the EHR in 2019. RESULTS: The prevalence of multimorbidity increased with increasing weight levels (12.3% in overweight and 33.4% in class 3 obesity for ages 19-40 years; 41.5% and 66.6% for ages 41-65 years; and 70.6%-85.9% for age >= 65 years). Ages for predicted 50% risk of having at least 2 ORCs were 59, 54, 49, and 43 years among patients with overweight and obesity classes 1, 2, and 3, respectively. The mean effect of multimorbidity on ORC-related costs was beyond additive in those with obesity, such that the ORC-related costs were about $1,082 (151%), $1,696 (218%), and $2,433 (264%) for class 1, class 2, and class 3 obesity, respectively. This effect was not present for overweight, for which the cost was $310 (42%). Individuals with multimorbidity had higher odds of emergency department visits (odds ratio [OR] = 1.74; 95% CI = 1.73-1.76) and inpatient hospitalization (OR = 3.32; 95% CI = 3.27-3 .38). CONCLUSIONS: The prevalence of obesity-related multimorbidity increased with increasing weight classes within age groups. Obesity- related multimorbidity presented at an earlier age with higher weight class, such that the predicted probability of having obesity-related multimorbidity was more than a decade younger in class 2 and class 3 obesity compared with overweight. It was associated with increased HCRU and higher-than-expected costs exceeding the sum for the ORCs. Early diagnosis and treatment of obesity may be needed to prevent or delay the onset of obesity-related multimorbidity and limit its associated health care costs.

Abstract Disclosure: K. Ezendu: Employee; Self; Eli Lilly & Company. G. Pohl: Employee; Self; Eli Lilly & Company. Stock Owner; Self; Eli Lilly & Company. C.J. Lee: Employee; Self; Eli Lilly & Company. Stock Owner; Self; Eli Lilly & Company. H. Wang: None. X. Li: Employee; Self; Eli Lilly & Company. Stock Owner; Self; Eli Lilly & Company. J.P. Dunn: Employee; Self; Eli Lilly & Company. Stock Owner; Self; Eli Lilly & Company. Background: Multimorbidity is an individual and healthcare system burden. Increased multimorbidity occurs with both excess weight and aging. We aim to determine the burden of multimorbidity as BMI class increases in various age groups of people with obesity or overweight. Methods: The study cohorts were derived from extracts of Optum’s de-identified Market Clarity Data with linked electronic health records (EHR) and claims database. Patients were classified into four weight classes based on their median body mass index (BMI) in 2019 [overweight (BMI 25 - <30kg/m2 or 23 - <25kg/m2 for Asians), class 1 obesity (30 - <35kg/m2 or 25 - <27.5 kg/m2 for Asians ), class 2 obesity (35 - <40kg/m2 or 27.5 - <40 kg/m2 for Asians), and class 3 obesity (≥40kg/m2)] and three age groups: 19-40, 41-65 and > 65 years. People were required to be continuously insured in 2018 and 2019 and have at least one BMI in 2019. People aged <19 or >80 years, with any BMI >60 kg/m2 or with deviation from their 2019 median BMI of ≥5%, cancer diagnosis, pregnancy or childbirth in 2018 or 2019, HIV/AIDS, Cushing disease or Prader-Willi syndrome were excluded. The presence, as of December 31, 2019, of 17 obesity-related comorbidities (ORCs) was determined using ICD-10 codes in EHR or insurance claims: heart failure, atrial fibrillation, cerebrovascular disease, coronary artery disease, peripheral artery disease, hypertension, dyslipidemia, asthma, depression/anxiety, osteoarthritis, gout, chronic kidney disease, obstructive sleep apnea, non-alcoholic steatohepatitis, low back pain, type 2 diabetes, reproductive diseases. Multimorbidity was defined as having 2 or more ORCs. Results: 2,147,223 people were analyzed. Mean age was 51 years with 25.1 %, 58.0%, and 16.9% in the 3 age groups 19-40, 41-65 and >65, respectively. Females were 52%; and Caucasians, 77.9%; Blacks, 11.8%; and Asians, 1.9%. For people aged 19-40 years, prevalence of multimorbidity was 12.3%, 17.8%, 23.5%, and 33.5% for overweight, class 1, class 2, and class 3 obesity, respectively; 41.5%, 51.3%, 58.6% and 66.6% for people aged 41-65 years; and 70.6%, 78.9%, 81.8% and 85.9% for people aged >65 years. Discussion and Conclusion: In people with obesity or overweight, the burden of multimorbidity increased as BMI classes increased regardless of age group. While multimorbidity was especially high in those >65years (70-85%), the younger age groups also had substantial burden of multimorbidity with one in three adults with class 3 obesity in age 19-40 group reporting multimorbidity. Further research is warranted on better understanding the adverse impact of weight-related multimorbidity on the individual and society. Presentation: Saturday, June 17, 2023

Letter to the Editor Pain Freedom at 2 to 8 Hours With Lasmiditan: A Comparison With Rimegepant and Ubrogepant Erin G. Doty MD, Corresponding Author Erin G. Doty MD doty_erin_gautier@lilly.com Eli Lilly and Company, Indianapolis, IN, USASearch for more papers by this authorJohn H. Krege MD, John H. Krege MD Eli Lilly and Company, Indianapolis, IN, USASearch for more papers by this authorGerhardt Pohl PhD, Gerhardt Pohl PhD Eli Lilly and Company, Indianapolis, IN, USASearch for more papers by this authorMichael Case PhD, Michael Case PhD Eli Lilly and Company, Indianapolis, IN, USASearch for more papers by this authorSherie A. Dowsett PhD, Sherie A. Dowsett PhD Eli Lilly and Company, Indianapolis, IN, USASearch for more papers by this authorStewart J. Tepper MD, Stewart J. Tepper MD Geisel School of Medicine at Dartmouth, Hanover, NH, USASearch for more papers by this author Erin G. Doty MD, Corresponding Author Erin G. Doty MD doty_erin_gautier@lilly.com Eli Lilly and Company, Indianapolis, IN, USASearch for more papers by this authorJohn H. Krege MD, John H. Krege MD Eli Lilly and Company, Indianapolis, IN, USASearch for more papers by this authorGerhardt Pohl PhD, Gerhardt Pohl PhD Eli Lilly and Company, Indianapolis, IN, USASearch for more papers by this authorMichael Case PhD, Michael Case PhD Eli Lilly and Company, Indianapolis, IN, USASearch for more papers by this authorSherie A. Dowsett PhD, Sherie A. Dowsett PhD Eli Lilly and Company, Indianapolis, IN, USASearch for more papers by this authorStewart J. Tepper MD, Stewart J. Tepper MD Geisel School of Medicine at Dartmouth, Hanover, NH, USASearch for more papers by this author First published: 22 July 2020 https://doi.org/10.1111/head.13899Citations: 6 Conflicts of Interest: EGD, JHK, GP, MC, SAD – full-time employees and minor stockholders, Eli Lilly and Company. ST – Grants for research (no personal compensation): Alder, Allergan, Amgen, Dr. Reddy's, ElectroCore, Eli Lilly and Company, eNeura, Neurolief, Novartis, Scion Neurostim, Teva, Zosano. Consultant and/or Advisory Boards (honoraria): Acorda, Alder, Alexsa, Align Strategies, Allergan, AlphaSights, Amgen, Aperture Venture Partners, Aralez Pharmaceuticals Canada, Axsome Therapeutics, Becker Pharmaceutical Consulting, BioDelivery Sciences International, Biohaven, Charleston Labs, Decision Resources, DeepBench, ElectroCore, Eli Lilly and Company, eNeura, Equinox, ExpertConnect, GLG, GSK, Guidepoint Global, Healthcare Consultancy Group, Health Science Communications, Impel, Lundbeck, M3 Global Research, Magellan Rx Management, Marcia Berenson Connected Research and Consulting, Medicxi, Navigant Consulting, Neurolief, Nordic BioTech, Novartis, Pfizer, Pulmatrix, Reckner Healthcare, Relevale, Revance, SAI MedPartners, Satsuma, Scion Neurostim, Slingshot Insights, Sorrento, Spherix Global Insights, Sudler and Hennessey, Synapse Medical Communications, Teva, Theranica, Thought Leader Select, Trinity Partners, XOC, Zosano. Salary: Dartmouth-Hitchcock Medical Center, American Headache Society. Stock options: Nocira, Percept. CME honoraria: American Academy of Neurology, American Headache Society, Cleveland Clinic Foundation, Diamond Headache Clinic, Elsevier, Forefront Collaborative, Hamilton General Hospital, Ontario, Canada, Headache Cooperative of New England, Henry Ford Hospital, Detroit, Inova, Medical Learning Institute PeerView, Miller Medical Communications, North American Center for CME, Physicians' Education Resource, Rockpointe, WebMD/Medscape Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Citing Literature Volume60, Issue8September 2020Pages 1793-1796 RelatedInformation

OBJECTIVES:To examine the effect of the Medicare Annual Wellness Visit (AWV) on the detection of cognitive impairment and on follow-up cognitive care for older adults.DESIGN:Retrospective matched-cohort study.SETTING:United States.PARTICIPANTS:A 5% random sample of fee-for-service Medicare beneficiaries continuously enrolled for 12 months before and after an index ambulatory visit occurring from 2011 to 2013 with no claims evidence of cognitive impairment before index.MEASUREMENTS:Outcomes include 12-month post-index visit claims-based measurements of cognitive impairment, including new Alzheimer's disease and related dementia (ADRD) diagnoses; medications for ADRD; and cognitive care-related diagnostic examination such as neurobehavioral testing, brain imaging, and blood tests for thyroid-stimulating hormone (TSH), serum B12, folate, and syphilis. We also measured changes in burden of anticholinergic medication.RESULTS:There were no clinically relevant differences between the AWV and control groups in the rates of incident ADRD diagnoses (6.16% vs 6.86%, p<.001) and initiation of ADRD medications (1.00% vs 1.08%, p=.15), although there were differences favoring the AWV group in rates of TSH (39.80% vs 28.36%, p<.001), B12 (9.41% vs 6.97%, p<.001), folate (4.76% vs 3.72%, p<.001), and neurobehavioral (0.75% vs 0.55%, p<.001) testing.CONCLUSIONS:Although the AWV is correlated with an increase in some measures of cognitive care, such as laboratory testing for reversible causes of cognitive impairment, it does not appear to substantially increase recognition of undetected ADRD.

One goal of the Medicare Annual Wellness Visit (AWV) is to detect possible cognitive impairment and, if found, facilitate further diagnostic evaluation and care planning. It is unknown if the AWV has an impact on measurable provider-initiated interventions regarding cognition. This study examined the impact of the AWV on receipt of diagnosis and anti-dementia medication. A 5% random sample of fee-for-service Medicare beneficiaries was stratified into two cohorts based on receipt of an AWV vs. an outpatient or physician office visit in a general practice or geriatric medicine setting in 2011, 2012, or 2013. Beneficiaries were required to have continuous Parts A, B, and D enrollment for 12 months pre- and post-index with no evidence of pre-existing cognitive impairment in the year prior to index. Cohorts were matched 1:1 on core-based statistical area, month of index, age, gender, race, comorbidity burden, and presence of depression. Claims with incident diagnoses or use of anti-dementia medications were compared between the groups in the 12 months post-index visit. Additionally, we measured absolute anticholinergic medication burden during a 3-month period prior to index and compared to a 3-month period starting 90 days after index (to allow time for claims to track tapering when necessary). No differences in rates of incident diagnoses or use of anti-dementia medications favoring AWV were found. A slightly greater (statistically significant but not clinically meaningful) increase in anti-cholinergic burden was observed for the AWV group. Despite the intention to increase detection of cognitive impairment and appropriate follow-up care, we did not find an impact of the AWV on receipt of diagnosis and treatment as measured by Medicare claims. Further analyses of other markers of cognitive care such as laboratory testing and diagnostic imaging are important outcomes we will explore in the future. Studies that aim to measure the impact of policies such as the AWV on cognitive outcomes would benefit from the use of clinical data that include types of screening tools used, results of the screening and other provider-initiated interventions after impairment is detected. Distribution of AWV Usage in 2013 among Eligible Beneficiaries by Core-Based Statistical Area (CBSA).

AIM:To assess the cost-effectiveness of first-line pemetrexed/platinum and other commonly administered regimens in a representative US elderly population with advanced non-squamous non-small cell lung cancer (NSCLC).MATERIALS AND METHODS:This study utilized the Surveillance Epidemiology and End Results (SEER) cancer registry linked to Medicare claims records. The study population included all SEER-Medicare patients diagnosed in 2008-2009 with advanced non-squamous NSCLC (stages IIIB-IV) as their only primary cancer and who started chemotherapy within 90 days of diagnosis. The study evaluated the four most commonly observed first-line regimens: paclitaxel/carboplatin, platinum monotherapy, pemetrexed/platinum, and paclitaxel/carboplatin/bevacizumab. Overall survival and total healthcare cost comparisons as well as incremental cost-effectiveness ratios (ICERs) were calculated for pemetrexed/platinum vs each of the other three. Unstratified analyses and analyses stratified by initial disease stage were conducted.RESULTS:The final study population consisted of 2,461 patients. Greater administrative censorship of pemetrexed recipients at the end of the study period disproportionately reduced the observed mean survival for pemetrexed/platinum recipients. The disease stage-stratified ICER analysis found that the pemetrexed/platinum incurred total Medicare costs of $536,424 and $283,560 per observed additional year of life relative to platinum monotherapy and paclitaxel/carboplatin, respectively. The pemetrexed/platinum vs triplet comparator analysis indicated that pemetrexed/platinum was associated with considerably lower total Medicare costs, with no appreciable survival difference.LIMITATIONS:Limitations included differential censorship of the study regimen recipients and differential administration of radiotherapy.CONCLUSIONS:Pemetrexed/platinum yielded either improved survival at increased cost or similar survival at reduced cost relative to comparator regimens in the treatment of advanced non-squamous NSCLC. Limitations in the study methodology suggest that the observed pemetrexed survival benefit was likely conservative.

BACKGROUND:Patients with non-small cell lung cancer (NSCLC) experience adverse physical symptoms because of cancer, cancer treatment, and comorbidities. The relations among Cancer-Related Symptoms, Functional Impairment, and Psychological Symptoms in patients with NSCLC is not well understood. METHODS:Retrospective analysis of patient-reported symptoms with the 38-item Patient Care Monitor survey, collected in routine clinical care for 1138 patients with NSCLC at eight US community oncology practices. Study sample was randomly split, and structural equation models examined the direct and mediated effects of Cancer-Related Symptoms and Functional Impairment on symptoms of acute distress (Distress) and depression (Despair) in the training sample. The training model was cross validated in testing sample. Results are presented for the full model using the entire sample. RESULTS:Patients were 48.3% female, with mean age of 66.0 years. The most common comorbidities were anemia (60.8%) and respiratory disease (24.5%). Severity of Cancer-Related Symptoms was strongly and positively related to Functional Impairment and Psychological Symptoms in both training and testing models. The modeled effect of Functional Impairment on Distress and Despair was significant in the overall model using the total sample, and significant or near-significant in the training and testing models. The mediated effect of Cancer-Related Symptoms by Functional Impairment tended to be weaker than its direct modeled effect on Distress and Despair. CONCLUSIONS:Despite prior research suggesting that Functional Impairment plays a larger role than symptom burden in depression in NSCLC, the independent modeled effects of Functional Impairment were no greater than the direct modeled effects of Cancer-Related Symptoms. Copyright © 2016 John Wiley & Sons, Ltd.

PURPOSE:Non-CML myeloproliferative neoplasms (MPN) include essential thrombocythemia (ET), polycythemia vera (PV), and myelofibrosis (MF). Reported median overall survival (OS) ranges from a few to several years for MF, a decade or more for ET and PV. The study objective was to compare US survival rates of ET, PV, and MF patients with matched non-MPN/non-cancer controls in a nationally representative database.PATIENTS AND METHODS:Data were taken retrospectively from the Survey, Epidemiology, and End Results (SEER)-Medicare linked database. Medicare enrollees with a new SEER MPN diagnosis between Jan 1, 2001 and Dec 31, 2007 were eligible. First MPN diagnosis was required at or after Medicare enrollment to allow for continuous follow-up. Non-MPN/non-cancer control groups were selected from Medicare separately for each MPN subtype and demographically matched to cases at a ratio of 5:1. Survival was determined starting from the case diagnosis date using the Kaplan-Meier method.RESULTS:A total of 3,364 MPN patients (n = 1,217 ET; 1,625 PV; 522 MF) met the inclusion criteria and were matched to controls. Mean age was 78.4, 76.1, and 77.4 years for ET, PV, and MF, respectively, and percent female was 63, 50, and 41. Median OS was significantly (p<0.05) lower for MPN cases vs. controls (ET: 68 vs. 101 months; PV: 65 vs. 104; MF: 24 vs. 106).CONCLUSIONS:In the US Medicare population, survival in MF patients was worse than that of patients with ET or PV and significantly worse than matched controls. Survival of patients with ET or PV was substantially inferior to matched controls. These findings have implications for the clinical management of MPN patients and underscore the need for effective therapies in all MPN subtypes.

BACKGROUND:Limited data exist regarding real-world treatment patterns, resource utilization, and costs of extensive-stage small cell lung cancer (esSCLC) among elderly patients in the United States. While abundant data are available on treatment patterns in metastatic non-small cell lung cancer (mNSCLC), to our knowledge no data exist comparing costs and resource use between patients with esSCLC or mNSCLC.METHODS:We retrospectively analyzed administrative claims data (2000-2008) of patients aged ≥65 years from the linked Surveillance, Epidemiology and End Results (SEER)-Medicare database. Patients were selected on the basis of having newly diagnosed esSCLC (n=5,855) or mNSCLC (n=24,090) during 1/1/2000-12/31/2005, and were required to have received cancer-directed therapy. Survival and other measures were compared between esSCLC and mNSCLC patients using Kaplan-Meier log-rank and univariate chi-square and t-tests. Study measures were followed from first diagnosis date of either esSCLC or mNSCLC until the earlier of death or end of the database.RESULTS:Survival between the cohorts did not differ significantly: mean of 10.4 months for esSCLC patients versus 11.1 months for mNSCLC; median survival was 7.4 months versus 5.9 months. A higher percentage of mNSCLC patients (vs. esSCLC) received radiation therapy (75.6% vs. 65.4%; P < 0.001) and surgery (13.6% vs. 7.8%; P < 0.001) during the metastatic disease period. Conversely, a higher percentage of esSCLC patients than mNSCLC patients received chemotherapy (85.5% vs. 60.3%; P < 0.001), red blood-cell transfusion (20.7% vs. 10.9%; P < 0.001), platelet transfusion (5.6% vs. 1.8%; P < 0.001), and growth-factor support (59.0% vs. 39.5%; P < 0.001). esSCLC patients incurred higher lifetime disease-related costs ($44,167 vs. $37,932; P < 0.001) and all-cause costs ($70,549 vs. $67,176; P < 0.001) than mNSCLC patients.CONCLUSIONS:Lifetime total and disease-related costs per patient were high. Increased use of chemotherapy, supportive care therapies (including growth factors), and disease-related hospitalizations were observed in esSCLC patients as compared with mNSCLC patients. Disease-related and all-cause costs for esSCLC also exceeded those of mNSCLC, except for hospice and skilled nursing services. Survival and per-patient costs for both groups underscore the unmet medical need for more effective therapies in patients with esSCLC or mNSCLC.

Evidence from clinical trials supports the use of platinum agents in combination with pemetrexed or paclitaxel plus bevacizumab as first-line treatments of nonsquamous non-small cell lung cancer (NSCLC). This retrospective study was performed to evaluate survival outcomes of these select first-line treatments in a real-world clinical setting. Patients with advanced (Stage IIIB/IV) nonsquamous NSCLC who initiated treatment with pemetrexed/platinum (Pem/Plat [n=122]), carboplatin/paclitaxel+bevacizumab (C/Pac+Bev [n=440]), or carboplatin/paclitaxel (C/Pac [n=989]) from July 2006 to January 2010 were identified in the McKesson Specialty Health iKnowMed electronic health record database of US Oncology community practices. Patients were followed for at least one year or last available data stream to assess progression or death. Overall survival (OS) and progression-free survival (PFS) were calculated from treatment initiation to earliest of the following: progression (as defined by escalation in line of therapy), death, or end of study. Association between treatment and OS/PFS was assessed by using Kaplan-Meier and Cox regression analyses adjusting for age, gender, stage at diagnosis, Eastern Cooperative Oncology Group performance status, and comorbidity index. Patients treated with Pem/Plat had a median OS of 476 days compared to 348 days for C/Pac+Bev patients (adjusted hazard ratio [adj HR]: 0.81, p=0.156) and 280 days for C/Pac patients (adj HR: 0.70, p=0.012). Pem/Plat patients had a median PFS of 187 days compared to 225 days for C/Pac+Bev patients (adj HR: 0.86, p=0.224) and 170 days for C/Pac patients (adj HR: 0.78, p=0.038). HRs for OS and PFS, which controlled for possible confounding factors, were significantly improved for patients treated with Pem/Plat compared to C/Pac. For Pem/Plat compared to C/Pac+Bev, the HRs for both OS and PFS were not statistically significant at this sample size.

Background: Approximately 1.7 million Americans are diagnosed with cancer annually. There is an increasing demand for high-quality cancer care; however, what constitutes quality care is not well defined. There remains a gap in our knowledge regarding the current perceptions of what defines quality care.Objective: To review the current understanding and perspectives of key stakeholders regarding quality cancer care for adult patients with cancer who are receiving chemotherapy-based treatment regimens.Methods: This systematic qualitative literature review involved a search of MEDLINE and PubMed databases for articles that were published between January 2009 and May 2013 using a predefined search strategy with specific Medical Subject Headings terms encompassing 3 core concepts-cancer, chemotherapy, and quality of healthcare. Articles were eligible to be included if they focused on adult cancers, discussed quality indicators of cancer care or quality of care in the article's body, discussed treating cancer with chemotherapy, were conducted in the United States and with US respondents, and reported data about cancer quality that were obtained directly from stakeholders (eg, patients, caregivers, providers, payers, other healthcare professionals). Thematic analyses were conducted to assess the perspectives and the intersection of quality care issues from each stakeholder group that was identified, including patients, providers, and thought leaders.Results: The search strategy identified 542 articles that were reviewed for eligibility. Of these articles, 15 were eligible for inclusion in the study and reported perspectives from a total of 4934 participants. Patients with cancer, as well as providers, noted information needs, psychosocial support, responsibility for care, and coordination of care as important aspects of quality care. Providers also reported the importance of equity in cancer care and reimbursement concerns, whereas patients with cancer considered the timeliness of care an important factor. The perspectives of thought leaders focused on barriers to and facilitators of quality care.Conclusion: Thematic elements related to cancer quality were relatively consistent between patients and providers; no additional information was found regarding payer perspectives. The perspectives of these groups are important to consider as quality initiatives are being developed.

97 Background: Due to emerging evidence in 2007, the FDA issued warnings in the labeling of ESAs regarding use among cancer patients. Subsequently, ASCO/ASH clinical practice guidelines were also updated to recommend discontinuation of ESAs in patients who fail to respond within 6-8 weeks. METHODS Patients with breast, head and neck, cervical, non-small cell lung cancer, or multiple myeloma initiating ESAs during 1/1/2003 - 7/1/2011 were identified from EMRs in the ACORN Data Warehouse (ACORN, Memphis TN). The study included those with at least 6-8 weeks of ESA use with documented hemoglobin (Hb) values. Following the ASCO/ASH guidelines, patients were defined as non-responders if Hb increased < 1g/dL between baseline (≤ 28 days before ESA initiation) and response determination date (Hb assessment closest to day 56). Non-responders were further classified as continuers or discontinuers based on the presence of ESA treatment following determination of non-response. ESA use, adverse events, and costs were assessed using Chi-square test for comparisons. RESULTS A total of 1,198 patients were classified as non-responders (591 in pre-2007 and 607 in post-2007). ESA continuation rate was lower for post-2007 compared to pre-2007 (75% vs. 90%, p < 0.0001). CONCLUSIONS The percentage of patients continuing ESA treatment in the absence of Hb response has decreased since 2007, yet still remains high despite guideline recommendations. It is not clear from these data whether the increased risks and cost burden in these patients were offset by other positive outcomes. [Table: see text].

INTRODUCTION:This prospective observational study evaluated the effect of race on disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) in patients with NSCLC treated with second-line pemetrexed. PATIENTS AND METHODS:Eligibility criteria included stage IIIB or IV NSCLC patients receiving single-agent pemetrexed for second-line therapy in routine clinical practice. Noninferiority was evaluated using logistic regression analysis of DCR, controlling for predefined covariates. Noninferiority was considered if the upper 95% confidence bound on the adjusted odds ratio (OR) for Caucasian vs. African-American individuals was less than 1.78, corresponding to a difference in proportion of 14% assuming Caucasian individuals to have a DCR of approximately 50%. The bound was chosen to be half of the anticipated difference between treatment and no second-line treatment. PFS and OS were estimated using the Kaplan-Meier method. Tools were used to measure functional status and symptom burden. RESULTS:The unadjusted DCR was 43.7% (117/268) for Caucasian and 45.0% (27/60) for African-American individuals (unadjusted OR, 0.95; 95% confidence interval [CI], 0.54-1.66). The adjusted OR in the final logistic regression model was 0.82 (95% CI, 0.43-1.58). This upper 95% confidence bound was within the prespecified acceptable bound of 1.78. Median PFS times (months) were 2.7 (95% CI, 2.4-3.4) for Caucasian and 3.0 (95% CI, 2.3-4.7) for African-American individuals (P = .91). Median OS times (months) were 6.7 (95% CI, 5.7-7.9) for Caucasian and 6.9 (95% CI, 4.5-8.9) for African-American individuals (P = .92). Baseline and functional status after baseline assessment and mean symptom burden did not differ substantially among races. CONCLUSION:African-American race was not considered to be a significant predictor of disease control after second-line treatment with pemetrexed.

e20629 Background: Cancer-related fatigue can be attributed to both treatment (tx) and the disease. Fatigue is a common adverse event (AE) of cancer tx and can profoundly affect patient (pt) well-being. It is unclear how often fatigue is a reason for dose adjustment, treatment delays, and discontinuations. Methods: To assess fatigue in pemetrexed (pem)-treated pts, we conducted post-hoc analyses of a prospective observational study of non–small cell lung cancer (NSCLC). Pts who received ≥ 1 dose of pem in routine 2nd-line medical care settings (N=434) were included in the analysis.Pt-reported fatigue scores were obtained from the MD Anderson Symptom Inventory-Lung Cancer (0 - not present to 10 - as bad as you can imagine) at the beginning of cycles (C) 1, 2, 4, 6 and at tx end. Physician (phys)-reported scores were obtained from AE assessments (grades 1-4) at C 2, 4, 6 and at tx end. Associations between pt-/phys-reported fatigue and dose reduction/treatment delays were explored using chi-square/exact tests at each cycle. Logistic regression explored the association between severe fatigue occurrence and possible confounders (α=0.05). Results: The table shows phys-reported fatigue incidence (%). Overall, 94% of pts reported some fatigue across all assessed cycles with 83% of pts reporting fatigue at baseline; 47% of pts reported severe fatigue (score ≥7) overall with 29% reporting severe fatigue at baseline. A significant association between severe phys-reported fatigue and treatment delay was observed only at C2 (p=0.02). After adjusting for possible confounders, low income and age ≤70 years were associated with severe pt-reported fatigue. ECOG PS ≥1, stage IV disease, and historical fatigue were associated with severe phys-reported fatigue. General pt- and phys-reported fatigue did not differ among racial groups. Conclusions: While pts and phys reported similar amounts of fatigue in general, pt-reported incidence of severe fatigue was higher. Factors related to severe fatigue differed between pts and phys. Fatigue had little influence on tx adjustments. [Table: see text]

e20525 Background: While broadly utilized for treatment of anemia in cancer patients, treatment with Erythropoetin Stimulating Agents (ESAs) is contraindicated in patients who fail to respond within 6-8 weeks. This study examined rates of ESA response and rates of continued ESA use following non-response in five cancer cohorts treated by community-practice oncologists. Methods: Patients with breast, head and neck, cervical, non-small cell lung cancer, or multiple myeloma initiating ESAs on or before 7/1/2011 were identified from EMRs in the ACORN Data Warehouse (ACORN, Memphis TN). The study included those with at least 6-8 weeks of ESA use and documented hemoglobin (Hb) values ≤28 days before start of ESA (“baseline”) and anytime during day 43-70 of ESA treatment. Per ASCO/ASH guidelines, patients were noted as responders if Hb increased ≥1g/dL between baseline and the Hb value closest to day 56 in the 43-70 day window, and non-responders if Hb increased <1g/dL. Non-responders were further classified as continuing or discontinuing therapy based on record of ESA treatment following determination of non-response. Results: A total of 2,197 patients were studied. ESA response rate was 45%. For non-responders, 83% continued ESAs after determination of non-response. Hb increase at end of therapy among non-responders remained lower than for patients who demonstrated initial response. Additionally, non-responders received nominally longer treatment, with a mean exposure of 169 days. Conclusions: Among cancer patients, a majority of ESA non-responders remained on ESA treatment beyond the recommended response window as defined by ASCO/ASH guidelines. Moreover, non-responders remained on treatment longer than those who demonstrated an initial response. [Table: see text]

Abstract Abstract 4273 Background: Non-CML myeloproliferative neoplasms (MPNs), which include essential thrombocythemia (ET), polycythemia vera (PV), myelofibrosis (MF) and MPN not otherwise specified (MPN-NOS), are characterized by activation of JAK2 signaling and abnormal blood cell production. Median survival ranges from months to years for MF and up to a decade or more for PV and ET. Some symptomatic treatment options exist, but with the exception of hematopoietic stem cell transplant, none are curative. Although MPN incidence is highest in persons aged ≥65 years, little is known about overall health care utilization and costs in elderly persons with these diseases. MPNs are more prevalent in the elderly and therefore Medicare enrollees are a highly relevant source for US-based resource utilization and cost data for these diseases. Objective: To compare all-cause health care utilization and costs from four subtypes of elderly MPN patients (ET, PV, MF and MPN-NOS) with matched non-MPN/non-cancer controls. Methods: Retrospective data were taken from the Survey, Epidemiology, and End Results (SEER)-Medicare linked database in the US, which combines clinical information from the SEER cancer registry (MPN reporting has been required since 2001) with medical and pharmacy claims for Medicare enrollees. Patients with a new MPN diagnosis between Jan 1, 2001 and Dec 31, 2007 were selected and evaluated for all-cause health care utilization and costs from Jan 1, 2008 (index date) through Dec 31, 2008 (follow-up end date). Patients were classified by MPN subtype based on the most recent diagnosis information (ICD-O-3 from the SEER registry or ICD-9-CM from Medicare claims) before the index date. Patients who died before follow-up end, had HMO or discontinuous Medicare enrollment during the follow-up year, had enrollment based on end stage renal disease, or a diagnosis of a non-MPN malignancy before follow-up end were excluded from the study. Separate non-MPN/non-cancer control groups were selected for each MPN subtype and matched (5:1) on birth year, gender, ethnicity, geography, and reason for Medicare eligibility. Per patient health care utilization and costs during the follow-up year were aggregated and stratified by care setting. Costs were adjusted to 2010 US$ and represent amounts reimbursed by Medicare to providers. Costs were compared between MPN cases and controls using univariate t-tests. Results: A total of 1,355 MPN patients (n = 445 ET, 684 PV, 81 MF, 145 MPN-NOS) were identified for study inclusion and assigned matching controls. For ET, PV, MF and MPN-NOS cases, respectively, mean [SD] age at index was 75.5 [9.7], 70.8 [11.3], 70.8 [10.4] and 74.1 [8.9] years and % female was 69.0, 43.9, 54.3, and 55.2. Mean [SD] years between first MPN diagnosis and study index date was 3.1 [2.0], 3.4[1.9], 2.7 [2.0], and 3.1 [2.1] for ET, PV, MF and MPN-NOS cases, respectively. A significantly (p<0.05) higher proportion of MPN cases, regardless of subtype, had ≥1 hospitalization during follow-up vs. controls (ET vs. control: 22% vs. 16%, PV vs. control: 27% vs. 15%, MF vs. control: 31% vs. 12%, MPN-NOS vs. control: 36% vs. 17%). Mean [SD] total days of hospital care were similarly higher in MPN cases (ET vs. control: 2.7 [12.8] vs. 1.6 [6.6], PV vs. control: 2.6 [7.0] vs. 1.7 [9.5], MF vs. control: 2.5 [6.2] vs. 1.2 [5.9], MPN-NOS vs. control: 4.0 [10.0] vs. 2.1 [13.7]), although the PV vs. control difference was not statistically significant. The ER visit rate during follow-up was also significantly (p<0.05) higher in MPN cases (ET vs. control: 34% vs. 24%, PV vs. control: 38% vs. 25%, MF vs. control: 46% vs. 21%, MPN-NOS vs. control: 44% vs. 29%). All-cause costs for MPN cases vs. matched controls are presented in the figure. Mean total costs per patient, driven equally by inpatient and outpatient services, were significantly (p<0.001) higher in MPN cases (ET vs. control: $11,259 vs. $8,897, PV vs. control: $13,337 vs. $8,530, MF vs. control: $20,917 vs. $7,367, MPN-NOS vs. control: $20,174 vs. $9,800). Conclusions: Total health care costs during a given year for elderly patients with MPNs are 1.3 to 3 times higher (depending on subtype) than those of matched controls. These findings may help inform future cost effectiveness evaluations of novel MPN treatments, as well as decision making in the provision of optimal MPN care within a Medicare system in which resources are finite and must be allocated ethically and efficiently. Disclosures: Karve: RTI Health Solutions: Consultancy, Research Funding. Price:Eli Lilly and Company: Employment, Equity Ownership. Davis:Eli Lilly, Merck, GlaxoSmithKline, Bristol-Myers Squibb, Pfizer, Eisai, Sanof-Aventis, Gilead Sciences, MedImmune: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Pohl:Eli Lilly and Company: Employment, Equity Ownership. Walgren:Eli Lilly and Company: Employment, Equity Ownership.

Background: Second-line treatment with pemetrexed (Pem) has demonstrated safety and efficacy in NSCLC patients. A prospective observational study was conducted to evaluate the impact of race on disease control rate (DCR) in NSCLC patients treated with 2nd line Pem. This analysis focuses on the association of race with tolerability of treatment and patient-reported activities of daily living and symptoms.Methods: Patients with stage IIIB/IV NSCLC who received at least one dose of Pem for 2nd line treatment were eligible for the study. Tolerability of Pem was evaluated in two ways: reason for discontinuation of treatment and the worst post-baseline patient-reported outcomes (PROs). Treatment duration and reasons for discontinuation between Caucasians (C) and African Americans (AA), Asian Americans (AS), or Hispanics (H) were compared using log-rank and chi-square tests. Two PROs were evaluated: activities of daily living as measured by Older Americans Resource-Services - Instrumental Activities of Daily Living (IADL) and symptom burden as measured by M.D. Anderson Symptom Inventory-Lung Cancer (MDASI-LC). Total IADL score is the sum of seven items (cooking, driving, shopping, doing housework, handling finances, taking medication, talking on telephone) and ranges from 0-14, with higher scores indicating less ability to conduct activities. The MDASI-LC includes 19 items and is scored as four factors: general symptom severity (GSS) subscale, gastrointestinal symptoms, overall distress, and lung cancer related symptoms, with higher scores indicating greater burden. Scores range from 0-10, obtained by averaging individual symptoms. ‘Worst post-baseline’ PRO scores were evaluated and were compared between C and AA, AS, or H using Wilcoxon-Mann-Whitney tests. For robustness, comparisons were also adjusted for predefined covariates (e.g. age, gender, income, insurance, smoking status, ECOG PS, disease stage, histology) using linear regression and least square means (LSM). Analyses were not adjusted for multiplicity; significance level was set at 0.05.Results: Among 434 eligible patients (n=304 C, 65 AA, 37 AS, 28 H), 61.52% patients stopped treatment due to progression or death; only 9.45% patients stopped treatment due to lack of tolerability. Discontinuation due to lack of tolerability was not significantly different between C and AA, AS, or H, but AS had a significantly longer treatment duration than C (median: 4 vs. 3 cycles, p = 0.02). Post-baseline outcomes were obtained from 75.81% patients, which was comparable across racial groups (range of 74.34% to 82.14%). Among racial groups, baseline PRO scores did not differ significantly. Post-baseline PRO scores did not differ significantly between C and AA or H, but AS reported lower ‘worst post-baseline’ total IADL scores (1.79 vs. 3.12, p=0.02) and GSS scores (2.66 vs. 3.68, p=0.01) than C. After adjusting for covariates, GSS subscale remained significant for AS (LSM difference = -0.97, p=0.01), and AA reported higher GSS (LSM difference = 0.53, p=0.04) and overall distress (LSM difference = 0.85, p=0.02) than C.Conclusions: Consistent with the literature, Pem is well-tolerated in patients with NSCLC during 2nd line treatment. Generally, few differences in tolerability, activities of daily living, and symptom burden were observed among racial groups. Citation Format: Alex Adjei, Li Li, Katherine B. Winfree, Gerhardt Pohl, Eduardo Pennella, Allicia C. Girvan, Coleman K. Obasaju, Mark S. Walker, Edward J. Stepanski, Lee Schwartzberg. Tolerability of pemetrexed: Results from an observational study of second-line treatment of non-small cell lung cancer (NSCLC) among racial groups. [abstract]. In: Proceedings of the Fifth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2012 Oct 27-30; San Diego, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2012;21(10 Suppl):Abstract nr B57.

7101 Background: Limited data exist on real-world treatment patterns, healthcare utilization, and associated costs of advanced SCLC among elderly patients in the US, and there are no recent comparisons between patients with advanced SCLC and advanced NSCLC. Methods: We retrospectively analyzed administrative claims data for elderly patients (≥65 years) from the linked Surveillance, Epidemiology and End Results (SEER)-Medicare database for 2000-2008. Patients with a new diagnosis of distant stage lung cancer receiving cancer-directed therapy (ie, surgery, radiation, biologics, and/or chemotherapy) were grouped by tumor type (SCLC [n=5,855] vs NSCLC [n=24,090]). Survival was compared using Kaplan-Meier Log-rank; categorical measures with Chi-square statistics; and continuous measures with t-tests. Results: Compared to SCLC patients, a significantly greater proportion of patients with NSCLC received radiation therapy (75.6% vs 65.4%; p<0.001) and surgery (13.6% vs 7.8%; p<0.001). Chemotherapy was received by 85.5% of SCLC patients and 60.3% of NSCLC patients (p<0.001). Significantly higher proportions of SCLC patients also received red blood cell (20.7% vs 10.9; p<0.001) and platelet transfusions (5.6% vs 1.8%; p<0.001) as well as growth factor support (58.9% vs 39.5%; p<0.001). Survival did not differ significantly between groups (p=0.424), with the mean (10.4 months vs 11.1 months) and median (7.4 months vs 5.9 months) survival for SCLC and NSCLC noted accordingly. Total lifetime lung cancer-related costs ($44,167 vs $37,932; p<0.001) and all-cause costs ($70,548 vs $67,175; p<0.001) per patient for SCLC exceeded those for NSCLC. The primary drivers of cost included resource utilization across 3 care settings: hospitalizations, office visits, and hospital outpatient visits. Conclusions: Overall total lifetime and disease-related costs per advanced SCLC and NSCLC patient were high, and costs for SCLC exceeded those for NSCLC. Survival estimates coupled with per patient costs for both cancers underscores the unmet medical need for patients with distant stage SCLC and NSCLC.

Background: The association of race with clinical outcomes has been increasingly investigated in non-small cell lung cancer (NSCLC). This prospective observational study evaluated the impact of race on disease control rate (DCR) in patients with NSCLC treated with second-line pemetrexed. Our previous report of this study showed the DCR of African-Americans was non-inferior to that of Caucasians (C). This report compares outcomes for Asian-Americans (AS) and C. Methods: Patients with stage IIIB/IV NSCLC who received one prior chemotherapy regimen and second-line therapy with pemetrexed were eligible. The primary endpoint was DCR (complete/partial response or stable disease). Secondary endpoints were overall survival (OS), progression-free survival (PFS), and adverse events. Logistic regression was used to analyze the DCR after therapy, controlling for 15 predefined covariates including prognostic and socioeconomic factors. Survival was estimated using Kaplan-Meier and compared with a log-rank test. Analyses were not adjusted for multiple race comparisons. Results: Challenges in enrolling minorities led to a lower than anticipated enrollment (AS=37 vs. 200 planned; C=304 vs. 400 planned), leaving a small sample size from which to draw conclusions. The mean age was 65 years (range, 34-90) for AS and 66 years (range, 37-86) for C. There were 17 males/20 females in the AS group and 161 males/143 females in the C group. Most patients had stage IV disease (AS=78.4%; C=80.3%). A higher percentage of AS had adenocarcinoma (AS=89.2%; C=62.8%; p=0.004) and a higher percentage of C were current smokers (AS=0.0%; C=27.7%; p=0.0002). The mean number of cycles received was 5.8 for AS and 4.1 for C. For the evaluable patients (AS=30; C=268), the DCR was numerically higher for AS (53.3% vs. 43.7%, OR=0.609, 95% CI: 0.253-1.469), but this difference was not statistically significant (p=0.270). AS had a significantly longer unadjusted median OS and PFS than C: OS of 16.0 (95% CI: 5.75-16.0) vs. 6.73 months (95% CI: 5.65-7.92), p=0.041; PFS of 5.08 (95% CI: 2.50-11.1) vs. 2.66 months (95% CI: 2.40-3.35), p=0.045. Adverse events, regardless of causality, occurred in <15% of patients, except for fatigue (AS=60%; C=68%). Conclusions: Despite the small sample size, this study provides insight into characteristics and outcomes of AS treated with second-line pemetrexed. Citation Format: A A. Adjei, E Pennella, A C. Girvan, G Peltz, G Pohl, C Obasaju, K Winfree, M S. Walker, E J. Stepanski, L S. Schwartzberg. Asian-American response to pemetrexed: Results from an observational study of second-line treatment of non-small cell lung cancer. [abstract]. In: Proceedings of the Fifth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2012 Oct 27-30; San Diego, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2012;21(10 Suppl):Abstract nr B77.