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Aim: To develop a cognitive dysfunction (CD) focused questionnaire to evaluate caregiver burden in glioblastoma. Materials & methods: The survey was developed from stakeholder consultations and a pilot study, and disseminated at eight US academic cancer centers. Caregivers self-reported caring for an adult with glioblastoma and CD. Results: The 89-item survey covered demographics, CD symptoms and caregiver burden domains. Among 185 caregivers, most were white, educated females and reported memory problems as the most common CD symptom. An exposure-effect was observed, with increase in number of CD symptoms significantly associated with greater caregiver burden. Conclusion: This questionnaire could guide caregiver interventions and be adapted for use longitudinally, in community cancer settings, and in patients with brain metastases.

Background: Tumor mutational burden (TMB) is a potential biomarker to predict tumor response to immuno-oncology agents in patients with metastatic non-small cell lung cancer (NSCLC). Materials and Methods: A multi-site cohort study evaluated patients diagnosed with stage IV NSCLC between 2012 and 2019 who had received comprehensive genomic profiling (CGP) and any NSCLC-related treatment at 9 U.S. cancer centers. Baseline characteristics and clinical outcomes were compared between patients with TMB 10 showed a significant association towards longer overall survival (OS) (HR: 0.43, 95% CI: 0.21–0.88, p = 0.02) and progression-free survival (PFS) (HR: 0.43, 95% CI: 0.21–0.85, p = 0.02) in patients treated with first-line immunotherapy and tested by Foundation Medicine or Caris at treatment initiation. Conclusions: TMB levels greater than or equal to 10 mut/Mb, when tested by Foundation Medicine or Caris at treatment initiation, were significantly associated with improved OS and PFS among patients treated with first-line immunotherapy-containing regimens. Additional prospective research is warranted to validate this biomarker along with PD-L1 expression.

Background Glioblastoma is an incurable disease with a poor prognosis. For caregivers of people with glioblastoma, the burden of care can be high. Patients often present with different clinical characteristics, which may impact caregiver burden in different ways. This study aimed to evaluate associations between patient clinical characteristics and caregiver burden/quality of life (QoL). Methods Caregiver–patient dyads were enrolled at 7 academic cancer centers in the United States. Eligible caregiver participants were self-reported as the primary caregiver of an adult living with glioblastoma and completed a caregiver burden survey. Eligible patients were age ≥ 18 years at glioblastoma diagnosis and alive when their respective caregiver entered the study, with the presence of cognitive dysfunction confirmed by the caregiver. Data were analyzed with descriptive statistics and multivariable analyses. Results The final cohort included 167 dyads. Poor patient performance status resulted in patient difficulty with mental tasks, more caregiving tasks, and increased caregiving time. Language problems were reported in patients with left-sided lesions. Patient confusion was negatively associated with all caregiver domains: emotional health, social health, general health, ability to work, confidence in finances, and overall QoL. Better caregiver QoL was observed in patients with frontal lobe lesions versus non-frontal lobe lesions. Conclusion This study reinforced that patient performance status is a critical clinical factor that significantly affects caregiver burden, caregiving tasks, and caregiver time. Additionally, patient confusion affects multiple facets of caregiver burden/QoL. These results could be used to support guided intervention for caregiver support, customized to the patient experience.

BACKGROUND: Pancreatic cancer is associated with low median overall survival. Combination chemotherapy regimens FOLFIRINOX and gemcitabine with nab-paclitaxel (GemNab) are the new adjuvant treatment standards for resectable pancreatic cancer. PRODIGE-24 and APACT trials demonstrated superior clinical outcomes with FOLFIRINOX and GemNab, each vs gemcitabine monotherapy. OBJECTIVE: To evaluate the cost-effectiveness of FOLFIRINOX vs GemNab for resectable pancreatic cancer in adults from the U.S. payer perspective, in order to inform decision makers about which of these treatments is optimal. METHODS: A Markov model with 3 disease states (relapse free, progressive disease, and death) was developed. Cycle length was 1 month, and time horizon was 10 years. Transition probabilities were derived from PRODIGE-24 and APACT survival data. All cost and utility input parameters were obtained from published literature. Cost-effectiveness analysis was performed to obtain total costs, quality-adjusted life-years (QALYs), life-years (LYs), and incremental cost-effectiveness ratio (ICER). A 3% annual discount rate was applied to costs and outcomes. The effect of uncertainty on model parameters was assessed with 1-way and probabilistic sensitivity analysis (PSA). RESULTS: Our analysis estimated that the cost for FOLFIRINOX was $40,831 higher than GemNab ($99,669 vs. $58,837). Despite increased toxicity, FOLFIRINOX was associated with additional 0.18 QALYs and 0.25 LYs compared with GemNab (QALY: 1.65 vs. 1.47; LY: 2.09 vs. 1.84). The ICER for FOLFIRINOX vs GemNab was $226,841 per QALY and $163,325 per LY. FOLFIRINOX was not cost-effective at a willingness-to-pay (WTP) threshold of $200,000 per QALY, and this was confirmed by the PSA. CONCLUSIONS: Total monthly cost for FOLFIRINOX was approximately 1.7 times higher than GemNab. If the WTP threshold increases to or above $250,000 per QALY, FOLFIRINOX then becomes a cost-effective treatment option. DISCLOSURES: This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. The authors have no conflicts of interest to declare.

Glioblastoma is an incurable disease with a poor prognosis. For caregivers of people with glioblastoma, the burden of care can be high. Patients often present with different clinical characteristics, which may impact caregiver burden in different ways. This study aimed to evaluate associations between patient clinical characteristics and caregiver burden/quality of life (QoL).Caregiver-patient dyads were enrolled at 7 academic cancer centers in the United States. Eligible caregiver participants were self-reported as the primary caregiver of an adult living with glioblastoma and completed a caregiver burden survey. Eligible patients were age ≥ 18 years at glioblastoma diagnosis and alive when their respective caregiver entered the study, with the presence of cognitive dysfunction confirmed by the caregiver. Data were analyzed with descriptive statistics and multivariable analyses.The final cohort included 167 dyads. Poor patient performance status resulted in patient difficulty with mental tasks, more caregiving tasks, and increased caregiving time. Language problems were reported in patients with left-sided lesions. Patient confusion was negatively associated with all caregiver domains: emotional health, social health, general health, ability to work, confidence in finances, and overall QoL. Better caregiver QoL was observed in patients with frontal lobe lesions versus non-frontal lobe lesions.This study reinforced that patient performance status is a critical clinical factor that significantly affects caregiver burden, caregiving tasks, and caregiver time. Additionally, patient confusion affects multiple facets of caregiver burden/QoL. These results could be used to support guided intervention for caregiver support, customized to the patient experience.

Background: Inherited genetic variants can modify the cancer-chemopreventive effect of aspirin. We evaluated the clinical and economic value of genotype-guided aspirin use for colorectal cancer chemoprevention in average-risk individuals. Methods: A decision analytical model compared genotype-guided aspirin use versus no genetic testing, no aspirin. The model simulated 100,000 adults ≥50 years of age with average colorectal cancer and cardiovascular disease risk. Low-dose aspirin daily starting at age 50 years was recommended only for those with a genetic test result indicating a greater reduction in colorectal cancer risk with aspirin use. The primary outcomes were quality-adjusted life-years (QALY), costs, and incremental cost-effectiveness ratio (ICER). Results: The mean cost of using genotype-guided aspirin was $187,109 with 19.922 mean QALYs compared with $186,464 with 19.912 QALYs for no genetic testing, no aspirin. Genotype-guided aspirin yielded an ICER of $66,243 per QALY gained, and was cost-effective in 58% of simulations at the $100,000 willingness-to-pay threshold. Genotype-guided aspirin was associated with 1,461 fewer polyps developed, 510 fewer colorectal cancer cases, and 181 fewer colorectal cancer-related deaths. This strategy prevented 1,078 myocardial infarctions with 1,430 gastrointestinal bleeding events, and 323 intracranial hemorrhage cases compared with no genetic testing, no aspirin. Conclusions: Genotype-guided aspirin use for colorectal cancer chemoprevention may offer a cost-effective approach for the future management of average-risk individuals. Impact: A genotype-guided aspirin strategy may prevent colorectal cancer, colorectal cancer-related deaths, and myocardial infarctions, while minimizing bleeding adverse events. This model establishes a framework for genetically-guided aspirin use for targeted chemoprevention of colorectal cancer with application toward commercial testing in this population.

BACKGROUND GBM is an aggressive cancer with poor prognosis. We explored impact of disease on caregivers by characterizing caregiver burden and QOL associated with patient characteristics. METHODS Primary caregivers of living adult GBM patients with cognitive dysfunction completed a GBM-specific caregiver burden survey and the validated Caregiver Quality of Life Index–Cancer Scale (CQOLC). Patient data were abstracted from medical records (7/2018-4/2019). Patient characteristics were compared between highest and lowest tertile of CQOLC scores (range 0–140); higher scores suggest better QOL. RESULTS There were 140 patient-caregiver dyads enrolled in the study. Mean patient age was 57 years (range 24–63); majority white males (62.9%), unifocal lesion (90%) and normal activity level at diagnosis. Forty-percent had methylated MGMT promoter status. Caregivers were mostly white (61.4%), college-educated female spouses of similar age; 87.8% were caregiving for >6 months. Median CQOLC score was 82 (tertiles: < 76 and >92). More caregivers in the lowest vs highest CQOLC tertile reported ‘not employed due to caregiving’ (52.4% vs 12%, P< 0.01), ‘changes in patients’ personality’ (73.3% vs 42.6%, P< 0.01), ‘patient memory problems’ (93.5% vs 77.1%, P=0.02), and caring for patient with recurrence treated with ‘chemotherapy other than temozolomide’ ([TMZ], 27.7% vs 8.3%, P=0.01). There was > 10% difference in proportion of caregivers in the lowest vs highest CQOLC tertile for the following patient characteristics: largest lesion in right temporal lobe at baseline and partial resection at initial treatment. Conversely, there was > 10% difference in the highest vs lowest CQOLC tertile for Karnofsky score (> 80), largest lesion in right frontal lobe at baseline, surgical clean margins, TMZ for initial treatment, and surgery for recurrence. CONCLUSION Unemployment, patient personality/memory changes, and chemotherapy other than TMZ use had significant impact on caregiver burden/QoL. This may help identify caregivers to receive support and intervention.

46 Background: Alternative payment models (APMs) aim to address the rising cost of cancer care ($173 billion in 2020) by promoting high-value care. This study explored the challenges and opportunities associated with implementation of APMs in oncology practice sites across the U.S. Methods: A novel survey was created through literature review and a focus group of content experts and researchers. This survey was distributed electronically (Qualtrics) to oncology/hematology physicians (MDs) and quality officers (QOs) at U.S academic (AC) and community (CO) cancer centers from August 2020 to November 2020. Each participant reported on their center’s experience with APMs. A descriptive analysis was conducted. Results: A total of 136 sites were contacted and 28 sites (13AC/15CO) participated (21% response rate). There were 30 (67%) sites that implemented an APM, the most common was the CMS Oncology Care Models (CMS OCM) (87%, n=26), which typically took 6 months or less for implementation (66%, n=20) and was reported to improve benchmark performance (63%, n=10). The most common reasons APMs were not implemented were administrative complexity (53%, n=8); difficulty with alignment of multiple payers to APM (47%, n=7); and need for a median of 5 full-time hires. A larger number of QOs indicated participation in CMS OCM compared to MDs [94% (n=15) vs. 76% (n=11)]. The biggest difficulty experienced by MDs was adoption of innovation at site’s financial risk (43%, n=6) compared to QOs who focused on administrative and financial burden (43%, n=7). Community cancer sites were more likely to use APMs (100%, n=23) compared to AC sites (31%, n=7). The largest difficulty experienced by CO sites was adoption of innovations at their own financial risk (26%, n=6) compared to high costs, administrative burden and lack of payer engagement (29%, n=2 each) for AC sites. The most common challenge with incentives among CO sites was concerns with risk adjustment of quality measures (57%, n=13) compared to increased complexity of incentive compensation (57%, n=4) for AC sites. CO sites indicated that quality measure performance reviews were primarily conducted by administrative staff compared to clinical leaders for AC sites. Conclusions: Administrative burden and access to appropriate patient data inhibit the impact of APMs. MDs are primarily concerned about the penalties and financial risk, whereas QOs focus on administrative complexities. For CO and AC sites, the adoption and implementation of APMs to improve cost and care delivery was not without significant challenges. This study demonstrates the multifaceted impact APMs have on care delivery.

Context: IPSS-R is used to classify risk of disease progression and guide treatment decisions for patients with MDS. Recent data shows mutational profiling may improve the prognostic stratification of MDS. Minimal real-world evidence exists for this population. Objective: Assess treatment patterns and clinical outcomes in patients with MDS by IPSS-R risk scores. Design: A retrospective cohort study assessed real-world, patient-level data from adults diagnosed with MDS between 2010–2019 at HCI. All data were obtained from electronic medical records via chart review. Patients with intermediate to very-high IPSS-R scores comprised the higher-risk cohort. Results: Of 259 patients with MDS, 90 had an IPSS-R score at diagnosis, 65 patients who were not clinical trial participants were included. IPSS-R score distribution: 10/65 (15%) very low; 18/65 (28%) low, 14/65 (22%) intermediate, 15/65 (23%) high, and 8/65 (12%) very high. Average patient age was 68 years, 52% (n=34) of patients were female, 91% (n=59) were White, 8% (n=5) had autoimmune disorders, and 5% (n=3) had cerebrovascular disease. In the higher-risk cohort, hypomethylating agents (HMAs) were used to treat 62% (n=23) of patients (median 2 cycles), while 27% (n=10) received no MDS-directed therapy and 11% (n=4) received other MDS-related medications. Stem-cell transplant (SCT) was received more frequently (n=13, 35%) and sooner (median 4.8 months from diagnosis) by higher-risk patients compared with lower-risk patients (18%, n=5; median 15.0 months from diagnosis). Complete (CR) or partial response was achieved by 17% (n=4) of higher-risk patients treated with HMAs versus 7% (n=1) of lower-risk patients. Transfusion independence was achieved by 60% (n=3) of higher-risk and 100% (n=4) of lower-risk patients who received PLT or pRBC prior to treatment initiation. Disease progression or death occurred in 82% (n=53) of patients during the study period, with a median progression-free survival of 8.3 months and 25.3 months for higher-risk and lower-risk patients, respectively. Conclusions: These results show that higher-risk patients have a low likelihood of achieving and maintaining CR. Limited treatment options for patients with higher-risk MDS reveals a large unmet need. Specific genetic profiles may indicate the need for more aggressive treatments and management of relevant comorbidities.

e19034 Background: IPSS-R is used to classify risk of disease progression and guide treatment decisions for patients with MDS. Recent data shows mutational profiling may improve the prognostic stratification of MDS. Minimal real-world evidence exists for this population. Methods: A retrospective cohort study assessed real-world, patient-level data from adults diagnosed with MDS between 2010-2019 at HCI. All data were obtained from electronic medical records via chart review. IPSS-R scores were manually calculated from lab and cytogenetic data within 30 days of diagnosis. Patients with an intermediate to very-high IPSS-R score comprised the higher risk (HR) cohort. Primary objectives were to assess treatment patterns & clinical outcomes in the HR cohort. Results: Of the 259 MDS patients at HCI, 90 had an available IPSS-R score at diagnosis (ANC results were missing for 64% of cohort). After excluding clinical trial participants, 65 patients were included. Distribution of IPSS-R scores was: 15% very low (n = 10), 28% low (n = 18), 22% intermediate (n = 14), 23% high (n = 15), & 12% very high (n = 8). The average age of HR subjects was 67 years. 57% of HR patients were female (n = 21), 92% were white (n = 34), 8% (n = 3) had autoimmune disorders, & 8% (n = 3) had cerebrovascular disease. 14% (n = 5) of NGS-tested HR patients had TP53 alterations, while the most frequently altered gene was DNMT3A at 17% (n = 6). In the HR cohort, HMA was used to treat 62% of patients (n = 23) (median 2 cycles), while 27% (n = 10) received no MDS-related medication, and 11% (n = 4) received other MDS-related medications (lenalidomide, ruxolitinib, hydroxyurea). Second-line treatment was received by 9% of HR patients (n = 3). 35% of HR patients (n = 13) underwent stem-cell transplantation. Complete or partial response was achieved by 21% of HR patients treated with a HMA (n = 5); the remaining patients had stable disease (39%, n = 9), disease progression (26%, n = 6), or died (4%, n = 1). Transfusion independence was achieved by 60% of HMA-treated HR patients (n = 3) (median duration = 151 days from treatment initiation). Disease progression or death occurred in 89% of HR patients (n = 33) during the study period with a median progression free survival (PFS) of 8.3 months. PFS was significantly shorter for HR patients with TP53 alterations compared to wild-type (HR: 5.75, 95% CI (1.34-24.64)), using cox regression. Median overall survival for HR patients was 18.8 months. Conclusions: These results show HR patients have a low likelihood of achieving & maintaining complete remission. In addition, limited treatment options for HR patients further reveals a large unmet need. Specific genetic profiles may indicate the need for more aggressive treatments and management of relevant comorbidities. Updated results will be presented, including LR patients & economic outcomes.

The advent of next generation sequencing (NGS) technologies has advanced our understanding of the intrinsic biology of different gastrointestinal (GI) tumor types. The use of novel, more efficient sequencing platforms has improved turnaround times of sequencing results. This is providing real time opportunities to put precision medicine to the test. A number of early phase clinical trials are testing targeted therapies in unique molecularly characterized subsets of patients (baskets). While basket studies are gaining momentum, treatment failures serve to remind us that shifting from a histology-driven to a histology-agnostic approach is unlikely to be a failure-free strategy for a number of tumor types as recently learnt from vemurafenib failure in BRAF mutated metastatic colorectal cancer (mCRC). GI malignancies are clinically and molecularly heterogeneous. Unfortunately, development of biomarkers of response to therapy as well as targeted therapies for GI adenocarcinomas has fallen behind compared to other malignancies. Trastuzumab is the only FDA approved targeted therapy for GI adenocarcinomas for which a biomarker of response (HER2 amplifications) is available. In addition, RAS mutations are known to predict lack of response to epidermal growth factor receptor (EGFR) inhibitors in advanced colorectal cancer (CRC) patients. However, NGS has recently revealed that a number of actionable genetic aberrations are present at low prevalence across different GI malignancies. Prospective randomized clinical trials will determine whether matching actionable aberration with targeted therapy will contribute to improve survival in patients with GI malignancies. Here, we review current evidence for targeted therapies in GI malignancies, as well as application and pitfalls of NGS including tissue testing and liquid biopsies.

Supplemental Digital Content is available in the text., New melanoma therapies have shifted the expectations of patients and providers. Evaluating the impact of treatment characteristics may enhance shared decision making. A survey, including a discrete choice experiment, was utilized to evaluate perceived trade-offs of different melanoma treatments and to estimate out-of-pocket (OOP) willingness-to-pay (WTP) thresholds (January 2016 to March 2016). Participants included patients with melanoma at Huntsman Cancer Institute and their cancer care providers. Stakeholder focus groups were conducted to identify treatment attributes. Descriptive and comparative statistics and multinomial logit model were used to evaluate responses. Response rates were 41.9% (N = 220) for patients and 37.7% (N = 20) for providers. Immunotherapy and targeted therapy attributes considered important by participants were overall survival, immunotherapy-related side effects, and skin toxicities. Patients and providers had significantly different views of quality-of-life expectations, anxiety toward melanoma, trust to make treatment decisions, sharing concerns about treatment, time to discuss treatment, understanding OOP costs, and willingness to undergo/recommend treatment (half of the patients would undergo treatment if it was effective for > 24 months). Among patients, the average monthly OOP WTP for combination immunotherapy with nivolumab + ipilimumab was $ 2357 and for BRAF/MEK inhibitor was $1648. Among providers, these estimates were $ 2484 and $1350, respectively. Discordance existed between patients’ and providers’ perceptions about quality of life expectations, degree of anxiety, sharing of opinions, and progression-free survival. Our study suggests that patients and providers exhibit a higher OOP WTP for combination immunotherapy treatment compared with BRAF/MEK inhibitors, influenced predominately by overall survival expectations.

Background First-line treatment for metastatic renal cell carcinoma (mRCC) is rapidly changing. It currently includes VEGF targeted therapies (TT), multi-target tyrosine kinase inhibitors (TKIs), mTOR inhibitors, and immunotherapy. To optimize outcomes for individual patients, genomic markers of response to therapy are needed. Here, we aim to identify tumor-based genomic markers of response to VEGF TT to optimize treatment selection. Methods From an institutional database, primary tumor tissue was obtained from 79 patients with clear cell mRCC, and targeted sequencing was performed. Clinical outcomes were obtained retrospectively. Progression-free survival (PFS) on first-line VEGF TT was correlated to genomic alterations (GAs) using Kaplan-Meier methodology and Cox proportional hazard models. A composite model of significant GAs predicting PFS in the first-line setting was developed. Results Absence of VHL mutation was associated with inferior PFS on first-line VEGF TT. A trend for inferior PFS was observed with GAs in TP53 and FLT1 C/C variant. A composite model of these 3 GAs was associated with inferior PFS in a dose-dependent manner. Conclusion In mRCC, a composite model of TP53 mutation, wild type VHL, and FLT1 C/C variant strongly predicted PFS on first-line VEGF TT in a dose-dependent manner. These findings require external validation.

Clinical pharmacists are important contributors to the care of patients with cancer; it is therefore critical for oncology clinical pharmacists to stay current with new anticancer therapies. This review summarizes the epidemiology and pathogenesis of non-small cell lung cancer, including the most common genetic alterations, as well as the mechanism of action, clinical development, pharmacodynamics and pharmacokinetics of the anaplastic lymphoma kinase inhibitor ceritinib for the treatment of patients with anaplastic lymphoma kinase-positive non-small cell lung cancer. Targeted therapies based on the presence of specific mutations are an important development in the treatment of non-small cell lung cancer. However, acquired resistance to the first anaplastic lymphoma kinase-inhibitor approved by the U.S. Food and Drug Administration, crizotinib, is observed in almost half of patients treated with it. Ceritinib is an oral anaplastic lymphoma kinase-inhibitor that has demonstrated more potent antitumor activity than crizotinib in preclinical models. It was granted accelerated approval in 2014 to treat anaplastic lymphoma kinase-positive metastatic non-small cell lung cancer patients who have progressed on or are intolerant to crizotinib. Ceritinib represents an important alternative second-line therapy for patients with metastatic non-small cell lung cancer who have traditionally limited treatment options.

Background Genetic counseling by a Genetic Counselor (GC) is a requirement prior to genetic testing for cancer susceptibility genes (GC-mandate policy) for some insurers. This study evaluated the impact of this policy from the patient perspective. Methods Surveys were sent to individuals for whom their insurer ordered genetic testing for the cancer susceptibility genes BCRA1 and BRCA2 over a 1 year time period that spanned the introduction of a GC-mandate policy. Responses were assessed by time period (before/after policy introduction) and genetic test completion. Results The surveys were completed by 1247/4950 (25.7%) eligible individuals. After policy introduction, there was no change in the proportion of respondents who completed genetic testing (p = 0.13) or had a mutation (p = 0.55). Overall decisional conflict (uncertainty or feeling uninformed) around genetic testing did not change after policy introduction (p = 0.16), but was significantly higher among respondents who did not complete genetic testing (p

16 Background: GBM is a largely incurable, highly aggressive cancer with high incidence of CD. Caregivers face heightened stress with loved one’s limited life expectancy and additional duties. To better understand this unique group, a survey tool was developed to examine effect of CD on caregiver burden. Methods: Four of 10 planned academic centers are enrolling towards achieving 200+ completed surveys. The survey was developed step-wise: 1) literature review of primary brain tumors, Alzheimer’s disease, and dementia to identify domains; 2) focus groups with neurooncologists and American Brain Tumor Association advocates to narrow domains; 3) caregiver interviews to verify selected domains; 4) single-site pilot study to confirm content (n=20). Dyads with caregiver survey and respective patient’s clinical data are created as possible. Results: Complete data from 31 caregivers and 28 dyads enrolled at Huntsman Cancer Institute, University of Utah and University of California, Los Angeles are currently available. Response rate was 88% for caregivers and 90% for patients. Among caregivers, 87% were patient spouse/partner, 84% female, average age 56 years, 42% currently employed, 32% have no additional help, and 26% are primary caregivers for others. Patients were male (74%), average age 59 years, not working (84%), and being treated for initial diagnosis (67%). Proportion of caregivers performing ≥ 1 caregiving task, i.e. meal preparation, doubled from before to after diagnosis (48% vs. 97%). The majority of caregivers (90%) perceived memory problems in a loved one over last 14 days. Trouble remembering recent events or things interfered with 71% of caregivers’ daily life "somewhat", "quite a bit", or "very much". When ranking effect of CD on caregiver’s general quality of life on a scale of 0 (none) to 10 (significant), 60% and 23% of caregivers indicated ≥ 5 and ≥ 8, respectively. Caregivers’ responses to survey satisfaction questions showed only 23% feel enough is being done to understand caregiving in GBM and 76% were satisfied overall with the survey. Conclusions: Caregivers are affected daily and significantly by GBM-related CD. Results will be updated at time of presentation.

INTRODUCTION: Mutation of FLT3, a tyrosine kinase receptor, is one of the most common molecular alterations in AML. In 2017, the FDA approved midostaurin for treatment of newly diagnosed AML adult patients with FLT3 mutation. Understanding of utilization and costs associated with AML pre and post Midostaurin approval is warranted. The objectives of this study were to evaluate healthcare utilization and costs between FLT3-mutated AML patients and FLT3-wildtype AML patients, pre-midostaurin approval and among initial FLT3-mutated AML patients treated with midostaurin. METHODS: FLT3-tested AML patients treated with 7+3 induction chemotherapy prior to midostaurin approval, were identified retrospectively from 2007-2016 at Huntsman Cancer Institute. A separate sample of FLT3-mutated patients treated with midostaurin from May 2017 to June 2018 were also identified. Healthcare charges, which are the individual list prices set by the medical facility, were computed for inpatient, outpatient and emergency services in this study. Since cost data were not available, charges were converted to imputed costs by applying the 2013 CMS charge-to-cost ratio of 0.492. Health care utilization through inpatient, outpatient and emergency room visits were also evaluated for FLT3-mutated and FLT3-wildtype patients. RESULTS: Pre-midostaurin: One hundred patients (39 FLT3-mutated, 61 FLT3-wildtype) prior to the availability of midostaurin were identified with a median age of 53 years. Median number of AML related inpatient visits for the total sample was 5 (FLT3-mutated [5] vs FLT3-wildtype [6] p=0.1]. Median outpatient visits were 43 for the total sample (FLT-mutated [47] vs FLT3-wildtype [51], p=0.4). Healthcare costs were categorized as AML related and all-cause related costs. AML related costs, which included transplant costs, contributed to nearly 70% of all-cause healthcare costs on an average. Approximately 38% of total AML-related costs were attributable to induction therapy among FLT3-mutated patients, while 29% of total AML-related costs among wildtype patients were related to induction (p Midostaurin cohort: Five FLT3-mutated patients administered midostaurin during induction treatment were identified from 2017 and 2018. No significant differences were observed in health care utilization between pre-midostaurin FLT3-mutated patients and midostaurin-treated patients. Midostaurin-treated patients and pre-midostaurin FLT3-mutated patients had similar mean AML-related healthcare costs, with a downward trend in costs among midostaurin patients (Table 1). Majority of costs in both groups were incurred during inpatient setting. Approximately 32% of costs in both groups were attributable to physician or professional costs (Table 1). CONCLUSIONS: No significant differences were observed in healthcare utilization or imputed costs among FLT3-mutated patients before and after midostaurin approval. Patients with FLT3 mutations historically had higher health care utilization and costs, likely due to generally poorer prognosis, increased transplant rates and higher relapse rates associated with this mutation. Inpatient costs were higher for FLT3-mutated patients, mainly due to higher physician costs. The change in standard of care for patients with FLT3 mutations following the addition of midostaurin to 7+3 did not result in increased healthcare utilization or costs. However, the sample size for the midostaurin-treated patients was very small in this early analysis. Thus, these conclusions are preliminary in nature. SPONSORSHIP: Funding for this study was provided by Novartis Pharmaceuticals. Disclosures Unni: Novartis: Research Funding. Biskupiak:Novartis: Research Funding. Ndife:Novartis: Employment. Joseph:Amgen: Equity Ownership; Novartis Pharmaceuticals Corporation: Employment; Pfizer: Equity Ownership; Express Scripts: Equity Ownership. Bonifacio:Novartis: Employment. Stein:Agios: Consultancy; Bayer: Consultancy; Novartis: Consultancy; Pfizer: Consultancy; Daiichi Sankyo: Consultancy; Celgene: Consultancy. Shami:JSK Therapeutics: Employment, Other: stock ownership; Lone Star Thiotherapies: Other: stock ownership. Kovacsovics:Amgen: Honoraria, Research Funding; Abbvie: Research Funding. Brixner:University of Utah: Research Funding; Millcreek Outcomes Group: Equity Ownership; Gilead: Consultancy; AstraZeneca: Consultancy; AbbVie: Consultancy; Abbott: Consultancy; BD: Consultancy. Stenehjem:Novartis: Research Funding.

Introduction: Fms-like tyrosine kinase 3 (FLT3) gene mutation occurs in approximately 25-30% of acute myeloid leukemia (AML) cases and is associated with poor prognosis. Decreased overall survival is reported in FLT3-mutated vs. FLT3-wildtype. Midostaurin, a pan-targeted kinase inhibitor that inhibits activated FLT3 received FDA approval in April 2017 for adult patients with newly diagnosed FLT3-mutated AML in combination with standard cytarabine and daunorubicin induction and cytarabine consolidation. We report descriptive US clinical treatment patterns and outcomes in FLT3-mutated early midostaurin-users, historical FLT3-mutated patients prior to midostaurin approval, and historical FLT3-wildtype AML patients all treated with 7+3 induction therapy at an academic cancer specialty hospital to support the development of a larger database across several comprehensive cancer centers. Methods: This retrospective, observational study utilized ICD codes, tumor registry data, and pharmacy records from the Huntsman Cancer Institute (HCI) to identify AML patients treated with 7+3 induction chemotherapy from 2007 to July 2018. FLT3-mutated midostaurin-users treated with 7+3 induction including midostaurin from May 2017 to July 2018 comprise Group 1. Historical FLT3-mutated patients prior to midostaurin approval (non-users) and FLT3-wildtype patients comprise Groups 2 and 3, respectively. Complete response (CR), relapse rates, overall survival and treatment patterns were described. Results: A total of 105 patients met eligibility for inclusion in the study. Groups 1, 2, and 3 included five, 39 and 61 patients, respectively. Off-label midostaurin use in Group 1 after induction therapy was observed in one patient with post-consolidation monotherapy and salvage therapy in combination with ATRA (tretinoin) and CLAG (cladribine, cytarabine, and filgrastim). Following midostaurin approval, two FLT3-mutated patients received induction therapy without midostaurin due to enrollment in clinical trials that excluded midostaurin use for induction and consolidation therapy. These two patients were excluded from the study. Descriptive results of the comparative groups are summarized in Table 1. CR rate from induction therapy was 100% for Group 1, 90% for Group 2, and 77% for Group 3. The proportion of patients who received consolidation therapy was 60%, 74%, and 67%, and patients who maintained CR during consolidation therapy was 100%, 83%, and 49% for Groups 1, 2, and 3, respectively. Sixty-six percent of eligible Group 1 patients, 74% of Group 2 patients, and 54% of Group 3 patients received transplant. Median time from diagnosis to transplant was 81, 99, and 145 days for Groups 1, 2, and 3, respectively. The proportion of patients who received salvage therapy in Groups 1, 2, and 3 was 20%, 38%, and 56% respectively. Median follow-up was 6 months for Group 1, 14 months for Group 2, and 24 months for Group 3. After CR, 20% of Group 1, 49% of Group 2, and 59% of Group 3 relapsed. All Group 1 patients were alive at time of analysis while four Group 2, and eight Group 3 patients died during the study period. Discussion: Similar CR and relapse rates were observed between the comparative groups, although early use observations indicate improved response rates of induction therapy and consolidation therapy in a limited Group 1 sample. Patients in Group 1 and Group 2 underwent transplant earlier and more frequently than patients in Group 3, which may explain the higher relapse rate in Group 3. As this data resource is expanded across similar institutions, statistical comparisons of FLT3-mutated AML patients treated with and without midostaurin can be made. Sponsorship: Funding for this study was provided by Novartis Pharmaceuticals. Disclosures Unni: Novartis: Research Funding. Ndife:Novartis: Employment. Joseph:Novartis Pharmaceuticals Corporation: Employment; Amgen: Equity Ownership; Pfizer: Equity Ownership; Express Scripts: Equity Ownership. Bonifacio:Novartis: Employment. Stein:Novartis: Consultancy; Daiichi Sankyo: Consultancy; Agios: Consultancy; Bayer: Consultancy; Celgene: Consultancy; Pfizer: Consultancy. Shami:Lone Star Biotherapies: Equity Ownership; Pfizer: Consultancy; JSK Therapeutics: Employment, Equity Ownership, Membership on an entity's Board of Directors or advisory committees; Baston Biologics Company: Membership on an entity's Board of Directors or advisory committees. Kovacsovics:Amgen: Honoraria, Research Funding; Abbvie: Research Funding. Brixner:BD: Consultancy; Abbott: Consultancy; AbbVie: Consultancy; AstraZeneca: Consultancy; Gilead: Consultancy; Millcreek Outcomes Group: Equity Ownership; University of Utah: Research Funding. Stenehjem:Novartis: Research Funding.

Objective: To describe chronic hepatitis C virus (HCV) infection, including its epidemiology and pathophysiology; review current treatment options for HCV infection; recognize investigational agents being studied as part of interferon-free therapy; and summarize clinical trials for the new agents. Data sources: PubMed for 2004 through August 2014 using search terms hepatitis C, American Association for the Study of Liver Diseases, sofosbuvir, simeprevir, and as needed specific names of other agents in devel opment during this time; news articles and news releases about company actions with regard to clinical trials and filings for marketing approval in the United States. Study selection: At the discretion of the author based on clinical relevance of study and relevance to national guidelines for HCV therapy. Results: HCV infection is an important medical and public health problem in the United States and worldwide that can cause cirrhosis, hepatocellular carcinoma, and liver failure. The advent of newly developed targeted therapies is changing the treatment paradigm for this disease. Although traditional therapy with pegylated interferon and ribavirin remain therapeutic options, direct-acting agents such as sofosbuvir (Sovaldi—Gilead) and simeprevir (Olysio—Janssen) are producing faster, earlier, and improved treatment response with fewer adverse effects. The combination of anti-HCV agents and the duration of treatment are based on genotype, patient treatment status, and patient risk factors. The dramatic and sustained clearance of the virus with these drugs makes sustained virologic response a reality for patients who are unable to tolerate pegylated interferon. The downside is their high cost, which may make them economically unsustainable. However, for patients infected with HCV, the potential for a cure and improved quality of life may now be a reality. Conclusion: HCV, a well-known blood-borne disease associated with significant morbidity and mortality worldwide, can be effectively and safely treated with new anti-HCV agents such as SOF. While these new medications are in their early days of real-world practice, they offer hope that cure is truly possible.

Background Prior studies have demonstrated reduced frontal lobe volumes in depressed adolescents. In this study, frontal lobe gray and white matter volumes in adolescents with major depressive disorder were evaluated. Methods Nineteen depressed and thirty-eight healthy comparison adolescents were recruited for a magnetic resonance imaging study. Images were segmented into gray matter, white matter, and cerebrospinal fluid. Morphometric measurements of the whole brain and frontal lobe region were completed. Results Whole brain volumes were significantly smaller in depressed subjects compared with the healthy comparison subjects. Significantly smaller frontal white matter volumes and significantly larger frontal gray matter volumes were found in the depressed subjects, after controlling for age and whole brain volume. Conclusions These results are consistent with the hypothesis that a deficit in frontal volume exists during cortical development in adolescents with depression. Further studies are needed to assess whether volume differences resolve over time and the extent to which these differences influence response to treatment.

e18318 Background: Colonoscopy is the “gold standard” for colorectal cancer (CRC) screening. However, adherence rates are low and detection is not optimal. Concomitant aspirin chemoprevention is recommended by US Preventive Task Force, but bleeding complications can be limiting. Variant genotypes in aspirin metabolism can modify CRC and adenoma risk. Genotype guided aspirin (ggASA) use will identify a targeted average-risk population for maximal aspirin benefit while minimizing adverse events rates compared to the general population. We conducted a cost-effectiveness analysis (CEA) of primary chemoprevention in CRC using ggASA compared to no intervention, and colonoscopy ±general aspirin in healthy average-risk individuals. Methods: Our Markov decision analytical model consisted of 5 possible health states: no CRC/polyps, adenoma, pre-clinical CRC, CRC, and death. Model probabilities for CRC and its prevalence were estimated using SEER database and published literature. A microsimulation of 10,000 individuals aged 50-64 years was used to estimate cost-effectiveness from US payer perspective over lifetime. One way and probabilistic sensitivity analyses and model validation results will be reported in the final poster. Results: Our results suggest that compared to colonoscopy and no intervention, ggASA was associated with fewer CRC cases, and CRC-related deaths and MI cases. Compared to colonoscopy + general aspirin, ggASA was associated with fewer bleeding events, similar rates of CRC and CRC-related deaths, and fewer MI cases prevented. From a cost-effectiveness standpoint, ggASA use over a lifetime had the lowest costs and highest quality adjusted life years gained compared to other strategies, if testing costs were ignored. Once genetic testing costs exceeds $63, colonoscopy + general aspirin becomes the most cost effective strategy. Between genetic testing cost of $63-283, the costs of using ggASA per quality adjusted life year gained is below $100,000. Conclusions: Genotype-guided aspirin use precisely identifies an average-risk population, and lowers adverse events rates compared to general aspirin. The economic value of genotype-guided aspirin is dependent on the genetic testing costs.

66 Background: Clinical guidelines recommend RAS testing and BRAF testing in CRC and melanoma, respectively, to guide treatment (tx) decisions. However, there are limited data to support routine multi-gene profiling. This study evaluated the impact of multi-gene profiling on genomically-guided tx decisions in patients with CRC or melanoma. Methods: A retrospective cohort study using combined data from UUHC Electronic Warehouse, Huntsman Cancer Institute (HCI) tumor registry, ARUP laboratories, and Foundation Medicine. Included patients were treated at HCI for CRC or melanoma and had genomic profiling (2012-2016). The index date was date of first genomic profiling result and impact on practice was measured by rate of genomically-guided therapy use. Results: Among 127 genomically-profiled patients with CRC, 66 (52%) received therapy. Patients were predominantly male (64%), aged 57 years (median) at diagnosis, had advanced disease (52%), received three tx lines (mean) at baseline, and had three mutations (mean) detected. Actionable mutations, other than RAS,occurred in 43.9% of tested patients; and only 10.1% of these patients received genetically-guided tx. In the CRC cohort 55% are still receiving standard of care tx, and may benefit from testing results in the future. Among 186 genomically-profiled patients with melanoma, 123 (66.1%) received therapy. Patients were predominantly male (63%), aged 60 years (median) at diagnosis, diagnosed at earlier stages (68%), received two tx lines (mean) at baseline, and had two mutations (mean) detected. Actionable mutations, other than BRAF V600E/K, occurred in 14.6 % of tested patients; and only 5.6% of these patients received genetically-guided tx. In the Melanoma cohort 77% are still receiving standard tx. Actionable mutations and genomically guided tx decisions will be presented. Conclusions: Genomic profiling lead to modest increase in genetically-guided therapy. The incremental clinical and economic benefit of guideline-recommended testing needs further investigation by cancer type.

Objective: Contrast-induced nephropathy (CIN) is a complication which may develop after exposure to iodinated contrast media. The resulting acute kidney injury (AKI) is associated with an increase in both short- and long-term morbidity and mortality, increased hospital length of stay, and greater health care costs. The pathophysiological mechanism associated with the development of CIN remains unknown. This narrative review summarizes the pathophysiology, risk factors, and current evidence for the prevention of CIN. Data Sources: A MEDLINE literature search (2004-May 2014) was performed using search terms contrast-induced nephropathy and prevention. Additional references were identified from literature citations, review articles, and meta-analyses. Study Selection and Data Extraction: Abstracts of English-language human clinical trials that examined therapies for the prevention of CIN were evaluated. Studies that did not investigate a preventative intervention for CIN were excluded. Emphasis was placed on recent publications. Data Synthesis: A multitude of therapies focused on the prevention of CIN have been investigated. Unfortunately, many of these studies have produced negative and/or inconsistent results. There is a paucity of adequately designed clinical studies evaluating strategies for the prevention of CIN. However, the best data supports use of preprocedural hydration with isotonic solution as the standard of care for prophylaxis. Conclusion: Given the poor prognosis associated with CIN, there is need for improved methods to prevent it. At present, the best tools to protect patients from unnecessary risk for CIN are careful assessment of renal function, judicious use of procedures that utilize contrast media, and adequate hydration with isotonic solution.

610 Background: TKIs and statins alone can cause liver injury. When used together, there is additive risk for hepatotoxicity, as seen with pazopanib and simvastatin, and the potential for discontinuing TKI therapy. Liver enzyme abnormalities are also associated with mTORi. Hepatotoxicity from concurrent use of statins as a class with TKI or mTORi as a class in real world practice in mRCC has not been reported. Methods: This observational cohort study included adult patients treated with a TKI or mTORi for mRCC at the Huntsman Cancer Institute from 2004-2014. We performed a treatment line analysis. For each treatment line, CTCAE criteria were used to categorize maximum AST, ALT, and total bilirubin. Highest grade of any liver enzyme was compared between TKI with and without statin and between mTORi with and without statin (Fisher’s Exact test). Results: A total of 162 treatment lines were included. For TKI and statin, the three most common treatment line combinations were sunitinib and simvastatin (7), sunitinib and atorvastatin (4), and pazopanib and simvastatin (3). For mTORi and statin, the three most common treatment line combinations involved simvastatin with temsirolimus (7) and everolimus (3). Prevalence of hepatotoxicity is shown in the table. Conclusions: Our results show a trend toward significance in the prevalence of hepatotoxicity with concomitant mTORi and statin versus mTORi alone, perhaps explained by mTORi-mediated competitive inhibition of simvastatin (sensitive CYP 3A4 substrate). There was no difference in hepatotoxicity for TKI with or without statin, although there were few pazopanib and simvastatin combinations. Study limitations include the small sample size, limited number of TKI or mTORi and statin combinations, and retrospective study design. A larger study is needed to validate these findings. [Table: see text]

608 Background: PPIs may reduce TKI bioavailability resulting in reduced efficacy, shortened time on TKI treatment, and disease progression. Axitinib, sorafenib, and pazopanib exhibit pH-dependent solubility. Esomeprazole reduced the AUC and Cmax of pazopanib by 40%, but there was no significant interaction for sorafenib with omeprazole or axitinib with rabeprazole. In real world practice, the effect of PPIs as a class on the efficacy of TKIs as a class in mRCC has not been reported. Methods: This observational cohort study evaluated adult patients treated with a TKI for mRCC. Time on TKI treatment was defined as TKI initiation date to date of discontinuation, change in therapy, lost to follow-up, or death. We performed a treatment line analysis. Time on TKI treatment was compared between patients with and without concurrent PPI (Kaplan-Meier, log-rank). Results: Analysis included 128 treatment lines, including 49 TKI with PPI and 79 TKI with no PPI treatment lines. TKIs included sunitinib, pazopanib, sorafenib, and axitinib. PPIs included omeprazole, lansoprazole, esomeprazole, pantoprazole, and rabeprazole. The three most common TKI/PPI combinations involved omeprazole with sunitinib (26), pazopanib (13), and axitinib (3). No difference in time on TKI treatment with PPI (median 8.7 months) and with no PPI (median 7.0 months, p = 0.41) was observed. In pazopanib treatment lines, no difference in time on treatment was observed in those treated with omeprazole or esomeprazole (n = 14, median 4.8 months) compared to those without PPI (n = 18, median 1.7 months, p = 0.22). Conclusions: Among the TKI/PPI combinations evaluated, there was no difference in time to TKI discontinuation with or without concurrent PPI. This suggests that concurrent PPI does not affect time to discontinuation of TKI. Study limitations include the small sample size, limited number of TKI/PPI combinations, and retrospective study design. A larger study is needed to validate these findings.