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Aim: To understand physician visit patterns among patients with stage IV (including nonmetastatic [M0] and metastatic [M1] disease) urothelial carcinoma (UC) and understand factors associated with a timely referral to a medical oncologist and systemic treatment. Patients & methods: Retrospective analysis of Surveillance, Epidemiology and End Results-Medicare data. Results: First physician encounter was with a urologist (M0: 69%; M1: 53%) or primary care physician ([PCP]; M0: 19%, M1: 25%) for the majority of patients around UC diagnosis. After the index urologist encounter, most patients had a subsequent medical oncologist visit at a median of 52 days (M0: 69.5 days, M1: 33 days). In an adjusted model, older age, index PCP visit, higher comorbidities and M0 disease were negatively associated with a medical oncologist referral. Among those referred to a medical oncologist, older age, Hispanic or non-Hispanic Black race and not being married were negatively associated with subsequent chemotherapy receipt (p < 0.05). Conclusion: Many patients with advanced UC encounter multiple specialists during their disease course. Older patients or those with a first UC-related encounter with a PCP are less likely to be referred to medical oncology. Once referred to medical oncology, social determinants, including race and marital status, are relevant predictors of receiving chemotherapy.

Background Recently approved second‐generation androgen receptor inhibitors (SGARIs) for non‐metastatic castration‐resistant prostate cancer (nmCRPC) have similar efficacy but differ in safety profiles. We used a discrete choice experiment (DCE) to examine how nmCRPC patients and caregivers perceive the benefits versus risks of these new treatments. Methods An online DCE survey with 14 treatment choice questions was administered to nmCRPC patients and caregivers. Each choice question compared two hypothetical medication profiles varying in terms of 5 safety attributes (risk or severity of adverse events [AEs]: fatigue, skin rash, cognitive problems, serious fall, and serious fracture) and two efficacy attributes (duration of overall survival [OS] and time to pain progression). Random parameters logit models were used to estimate each attribute's relative importance. We also estimated the amounts of OS that respondents were willing to forego for a reduction in AEs. Results In total, 143 nmCRPC patients and 149 caregivers viewed the AEs in following order of importance (most to least): serious fracture, serious fall, cognitive problems, fatigue, and skin rash. On average, patients were willing to trade 5.8 and 4.0 months of OS to reduce the risk of serious fracture and fall, respectively, from 3% to 0%; caregivers were willing to trade 6.6 and 5.4 months of OS. Conclusions nmCRPC patients and caregivers preferred treatments with lower AE burdens and were willing to forego OS to reduce the risk and severity of AEs. Our results highlight the importance of carefully balancing risks and benefits when selecting treatments in this relatively asymptomatic population., Nonmetastatic castration‐resistant prostate cancer patients and caregivers preferred treatments with lower adverse event (AE) burden and were willing to forego survival to reduce the risks and severity of AEs. They viewed AEs in following order of importance (most to least): serious fracture, serious fall, cognitive problems, fatigue, and skin rash. It is important to carefully balance the risks and benefits when selecting treatments in this relatively asymptomatic population, especially given the differing AE profiles of newer treatments.

Supplemental digital content is available in the text., Objectives This analysis investigated nomogram use to evaluate metastatic pancreatic cancer prognosis. Methods Thirty-four baseline factors were examined in the Metastatic Pancreatic Adenocarcinoma Clinical Trial (MPACT) (nab-paclitaxel plus gemcitabine vs gemcitabine) data set. Factors significantly (P < 0.1) associated with overall survival (OS) in a univariable model or with known clinical relevance were tested further. In a multivariable model, factors associated with OS (P < 0.1) were selected to generate the primary nomogram, which was internally validated using bootstrapping, a concordance index, and calibration plots. Results Using data from 861 patients, 6 factors were retained (multivariable analysis): neutrophil-lymphocyte ratio, albumin level, Karnofsky performance status, sum of longest diameter of target lesions, presence of liver metastases, and previous Whipple procedure. The nomogram distinguished low-, medium-, and high-risk groups (concordance index, 0.67; 95% confidence interval, 0.65–0.69; median OS, 11.7, 8.0, and 3.3 months, respectively). Conclusions This nomogram may guide estimates of the range of OS outcomes and contribute to patient stratification in future prospective metastatic pancreatic cancer trials; however, external validation is required to improve estimate reliability and applicability to a general patient population. Caution should be exercised in interpreting these results for treatment decisions: patient characteristics could differ from those included in the nomogram development.

Introduction Hereditary (variant) transthyretin amyloidosis (ATTRv) with polyneuropathy (ATTR-PN) is a rare genetic disorder that causes progressive autonomic and sensorimotor neuropathy, severe disability, and death within 10 years of onset. Previous studies have primarily focused on how baseline cardiac characteristics affect mortality, but the impact of non-cardiac baseline characteristics is less defined. Methods We systematically searched PubMed/Medline (1990–2019) to identify studies that assessed the impact of baseline ATTR-PN characteristics on survival. Outcomes were first summarized descriptively. Extracted survival data were then disaggregated, and parametric mixture models were used to assess survival differences among patient groups defined by factors known to affect survival. Results The search yielded 1193 records, of which 35 were retained for analysis. Median survival ranged from 0.5 to > 25 years. The largest survival differences were between cohorts who underwent liver transplantation (LTx) versus those who did not. Among LTx cohorts, pre-LTx ATTR-PN disease duration ≥ 7 years, poor nutritional status, and late disease onset reduced median survival by 13, 12, and 10 years, respectively. Other prognostic survival factors included non-Val30Met genotype and baseline presence of urinary incontinence, erectile dysfunction, or muscle weakness. Conclusion Survival in patients with ATTR-PN is highly variable and affected by non-cardiac baseline characteristics, such as autonomic dysfunction, large fiber involvement, late-onset disease, and non-Val30Met mutation. Careful interpretation of these findings is warranted given that this synthesis did not control for differences between studies. Survival in patients with ATTR-PN remains poor among those who are untreated or with delayed diagnosis. Electronic supplementary material The online version of this article (10.1007/s40120-020-00183-7) contains supplementary material, which is available to authorized users.

Purpose To assess, from the Canadian public payer perspective, the cost-utility of implanting iStent Inject trabecular bypass stent (TBS) devices in conjunction with cataract surgery versus cataract surgery alone in patients with open-angle glaucoma (OAG) and visually significant cataract. Design Cost-utility analysis using efficacy and safety results of pivotal randomized clinical trial. Participants Modeled cohort of patients with OAG (83.1% with mild disease, 16.9% with moderate disease) and visually significant cataract. Methods Open-angle glaucoma treatment costs and effects were projected over a 15-year time horizon using a Markov model with Hodapp-Parrish-Anderson glaucoma stages (mild, moderate, advanced, severe or blind) and death as health states. Patients in the mild or moderate OAG health states received implantation of iStent Inject during cataract surgery versus cataract surgery alone. On worsening of visual field defect and optic disc damage, patients could receive selective laser trabeculoplasty and trabeculectomy. We measured treatment effect as reduction in intraocular pressure (IOP) and mean medication use and estimated transition probabilities based on efficacy-adjusted visual field mean deviation decline per month. Healthcare resource utilization and utility scores were obtained from the literature. Cost inputs (2017 Canadian dollars [C$]) were derived using the Ontario Health Insurance Plan, expert opinion, medication claims datasets, and Ontario Drug Benefit Formulary medication consumption costs. We conducted deterministic and probabilistic sensitivity analyses to examine the impact of alternative model input values on results. Main Outcome Measures Incremental cost per quality-adjusted life year (QALY) gained. Results Compared with cataract surgery alone, TBS plus cataract surgery showed a 99% probability of being more effective (+0.023 QALYs; 95% confidence interval [CI], 0.004 to 0.044) and a 73.7% probability of being cost-saving (net cost, –C$389.00; 95% CI, –C$1712.00 to C$850.70). In 95% of all simulations, TBS plus cataract surgery showed a cost per QALY of C$62 366 or less. Results were robust in additional sensitivity and scenario analyses. Conclusions iStent Inject TBS implantation during cataract surgery seems to be cost effective for reducing IOP in patients with mild to moderate OAG versus cataract surgery alone.

Aims: To describe the incidence and identify prognostic factors of central nervous system (CNS) adverse events (AEs) and any AEs (CNS, skin rash, or fracture) and evaluate the healthcare resource u...

Aim: We conducted this study to describe nonmetastatic castration-resistant prostate cancer (nmCRPC) patient characteristics and treatment patterns in the US, Europe and Japan. Materials & methods: Descriptive analyses were conducted using the 2015–2017 Ipsos Global Oncology Monitor Database. Results: A total of 2065 (442 in the US, 509 in Europe and 1114 in Japan) patients (median age: 74–80 years; stage III at diagnosis : 38.5%; Eastern Cooperative Oncology Group [ECOG] score ≤1: 79.4%; treated by urologist : 88.4%) were included in the analytic cohort. Luteinizing hormone-releasing hormone agonists and antiandrogens were the most commonly used first regimen treatments. With subsequent nmCRPC regimens their use decreased, while the use of chemotherapy, corticosteroids, androgen synthesis inhibitors and second-generation androgen receptor inhibitors increased. Conclusion: These data represent real-world treatment patterns in nmCRPC.

Introduction Insomnia diagnosis has been associated with a significant clinical and economic burden on patients and healthcare systems. This study examined changes in healthcare resource use (HCRU) and costs in insomnia patients before and after initiation of suvorexant treatment. Methods This retrospective cohort study analyzed Optum Clinformatics Data Mart claims data (Jan 2010–Dec 2018). Patients with ≥ 2 insomnia diagnosis claims and ≥ 1 prescription for suvorexant were included. Prevalent and incident insomnia patients were analyzed separately. The change in the trends of HCRU and costs were examined for 12 months before and 12 months after suvorexant initiation. An interrupted time series (ITS) analysis was conducted to assess the level and slope changes. Subgroups of patients with mental health comorbidities were examined. Results The study included 18,919 and 5939 patients in the prevalent and incident insomnia cohorts, respectively. For the prevalent cohort, mean (SD) age was 64.5 (14.1) years, 65% were female, 74% had Medicare Advantage coverage, and 61% had a Charlson comorbidity index score ≥ 1. Characteristics for the incident cohort were similar. The ITS results suggested that the trend for monthly total healthcare cost (THC) was increasing before suvorexant initiation (US$52.51 in the prevalent cohort, $74.93 in incident insomnia cohort), but, after suvorexant initiation, the monthly total cost showed a decreasing trend in both cohorts. The decrease in slope for THC after suvorexant initiation were $72.66 and $112.07 per month in the prevalent and incident cohorts, respectively. The monthly trends in HCRU rates also decreased. The subgroup analysis showed that decreases were 1.5–3 times greater for patients with mental health comorbidities. Conclusions In this real-world study, suvorexant initiation was associated with immediate and continued decreases in HCRU and costs in insomnia patients. Further research is needed to understand the effect of suvorexant initiation on direct medical costs as well as costs associated with lost productivity in other real-world settings. Supplementary Information The online version contains supplementary material available at 10.1007/s12325-021-01891-8.

Background Until recently, patients with myelodysplastic syndromes (MDSs) could receive hypomethylating agents (HMAs) via intravenous (IV) or subcutaneous (SC) administration. An oral HMA was recently approved as an alternative to IV/SC administration. This study assessed the impact of IV/SC HMA on MDS patients, and their experience of, challenges with, and views about oral MDS treatment. Patients and methods We conducted an online cross-sectional survey among adult MDS patients (or caregivers as proxies) invited by 2 U.S. MDS patient advocacy groups. Patients were required to have received IV/SC HMA (i.e., azacitidine or decitabine) within 6 months of the survey. Results The survey was completed by 141 participants (120 patients, 21 caregiver proxies). Median patient age was 63.0 years, 53.9% were female, and 19.8%, 62.4%, and 17.7% had lower-, higher-, or unknown risk scores, respectively. HMA treatment received included SC azacitidine (37%), IV azacitidine (36%), and IV decitabine (27%). Among 89 IV HMA recipients, 74.2% and 69.7% reported treatment-related interference with their social and daily activities, respectively, and 66.3% reported pain related to treatment administration. Following an injection, SC HMA recipients reported pain (94.2%) and interference with daily (86.5%) and social (80.8%) activities. Among the 49.6% of patients who were working, 61.4% felt less productive due to treatment. Most (69.5%) MDS patients indicated they would prefer oral MDS treatment to IV/SC therapies. Conclusion Patients receiving IV/SC HMAs experienced pain/discomfort and interference with social and daily activities. The introduction of an oral HMA may alleviate some treatment challenges for MDS patients. Micro-Abstract This cross-sectional online survey assessed treatment challenges among myelodysplastic syndrome (MDS) patients (including caregivers as proxies) who recently received treatment with hypomethylating agents (HMAs) via infusion/injection. Patients experienced pain/discomfort, interference with daily and social activities, and productivity loss. Respondents indicated a preference for oral MDS treatment. The introduction of oral HMA therapy may alleviate some treatment challenges for MDS patients.

Purpose To assess, from a United States (US) perspective, the cost-effectiveness of chemotherapy-induced nausea and vomiting (CINV) prophylaxis using a single dose of netupitant and palonosetron in a fixed combination (NEPA) versus aprepitant plus granisetron (APR + GRAN), each in combination with dexamethasone, in chemotherapy-naïve patients receiving highly emetogenic chemotherapy (HEC). Methods We analyzed patient-level outcomes over a 5-day post-HEC period from a randomized, double-blind, phase 3 clinical trial of NEPA (n = 412) versus APR + GRAN (n = 416). Costs and CINV-related utilities were assigned to each subject using published sources. Parameter uncertainty was addressed via multivariate probabilistic sensitivity analyses (PSA). Results Compared to APR + GRAN, NEPA resulted in a gain of 0.09 quality-adjusted life-days (QALDs) (4.04 vs 3.95; 95% CI −0.06 to 0.25) and a significant total per-patient cost reduction of $309 ($943 vs $1252; 95% CI $4–$626), due principally to $258 in lower medical costs of CINV-related events ($409 vs $668; 95% CI −$46 to $572) and $45 in lower study drug costs ($531 vs $577). In the PSA, NEPA resulted in lower costs and higher QALD in 86.5% of cases and cost ≤ $25,000 per quality-adjusted life-year gained in 97.8% of cases. Conclusions This first-ever economic analysis using patient-level data from a phase 3 trial comparing neurokinin-1 receptor antagonist (NK1 RA) antiemetic regimens suggests that NEPA is highly cost-effective (and in fact cost-saving) versus an aprepitant-based regimen in post-HEC CINV prevention. Actual savings may be higher, as we focused only on the first chemotherapy cycle and omitted the impact of CINV-related chemotherapy discontinuation. Electronic supplementary material The online version of this article (10.1007/s00520-019-04824-y) contains supplementary material, which is available to authorized users.

Aim: This analysis estimated the overall survival, treatment patterns and economic burden of elderly metastatic triple-negative breast cancer patients. Materials & methods: Patients (≥66 years) with metastatic triple-negative breast cancer were identified from the SEER-Medicare database. Treatment patterns were defined in terms of first, second and third or more regimens. Healthcare resource use and costs were reported over the follow-up period and over the treatment duration of each regimen. Results: A total of 51% of patients did not receive chemotherapy. Taxanes were most commonly used. Median survival was 7 months. The mean cumulative (per patient per month) cost per patient was US$73,586 (US$10,084). Mean cost in first and second regimen were US$26,950 and US$33,347. Conclusion: About half of patients did not receive chemotherapy. Receipt of increasing regimens led to higher mean costs and healthcare resource use.

To assess from a US payer perspective the cost-effectiveness of the chimeric antigen receptor T (CAR T)-cell therapies axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel) to treat relapsed or refractory (r/r) large B-cell lymphoma (LBCL) following ≥2 systemic therapy lines. A three-state (i.e. pre-progression, post-progression, and death) partitioned survival model was used to estimate the quality-adjusted life-years (QALYs) and costs for patients on each treatment over a lifetime horizon. Progression-free survival (PFS) and overall survival (OS) were based on a matching-adjusted indirect treatment comparison (MAIC) that accounted for differences in trial population baseline characteristics. Mixture cure models (MCMs) were used to account for long-term survivors. Costs included drug acquisition and administration for the CAR T-cell therapies and conditioning chemotherapy, apheresis, CAR T-specific monitoring, transplant, hospitalization, adverse events, routine care, and terminal care. Health state utilities were derived from trial and published data. Sensitivity analyses included probabilistic sensitivity analyses (PSAs) and an analysis of extremes that assessed the results across a vast array of combinations of parametric OS and PFS curves across the two therapies. Compared to tisa-cel, axi-cel resulted in 2.31 QALYs gained and a cost reduction of $1,407 in the base case. In the PSA, the cost per QALY gained was ≤$31,500 in 95% of the 1,000 simulations. In the analysis of extremes, the cost per QALY gained was ≤$7,500 in 99% of the 1,296 combinations of MCMs and ≤$40,000 in 95% of the 1,296 combinations of standard models. In absence of head-to-head comparative data, we relied on a MAIC, which cannot account for all possible confounders. Moreover, some outcomes (i.e. transplantations, hospitalizations, adverse events (AEs)) were not adjusted in the MAIC. In this simulation, axi-cel was a superior treatment option as it is predicted to achieve better outcomes at lower or minimal incremental costs versus tisa-cel.

Background: Although the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-PAN26 is widely used to assess health-related quality of life (HRQoL), its group-level minimal important difference (MID) and individual-level responder definition (RD) are not established; we calculated MID and RD using HRQoL data from the APACT trial in patients with surgically resected pancreatic cancer who received adjuvant chemotherapy. Methods: HRQoL was assessed using EORTC QLQ-C30 and QLQ-PAN26 at baseline, during treatment, at end of treatment, and during follow-up. Distribution-based MIDs were estimated using 0.5 × baseline standard deviation (SD) and reliability-based (intraclass correlation) standard error of measurement (SEM). Anchor-based MIDs and RDs (anchor, QLQ-C30 overall health) were estimated using a linear mixed model. Results: Overall, 772 patients completed the baseline assessment. Distribution-based MIDs (0.5 × SD) for QLQ-PAN26 scales ranged from 12 to 13, except hepatic symptoms (≈8), pancreatic pain (≈10), and sexual dysfunction (≈17); those for stand-alone items ranged from 12 to 16. The SEM values were similar. Among scales/items sufficiently correlated (r>0.30) with the anchor, MIDs ranged from 5 to 9. Within-patient QLQ-PAN26 RD estimates varied by direction (deterioration vs. improvement) and scale/item, but all values were lower than the true possible within-patient change (e.g. 16.7 points for a two-item scale) given a one-category change on the raw scale. Conclusions: Compared with distribution-based MIDs, anchor-based MIDs were twice as sensitive in detecting group-level changes in QLQ-PAN26 scales/items. For interpreting clinically meaningful change, RDs cannot be less than the true minimum of the scale. The group-level MID may help clinicians/researchers interpret HRQoL changes. Trial registration: ClinicalTrials.gov NCT01964430; Eudra CT 2013-003398-91.

Background Glioblastoma (GBM) is associated with poor prognosis, large morbidity burden, and limited treatment options. This analysis evaluated real-world treatment patterns, overall survival, resource use, and costs among Medicare patients with GBM. Methods This retrospective observational study evaluated Medicare patients age 66 years or older with newly diagnosed GBM using the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked data from 2007 through 2013. Patients were followed from diagnosis to death or end of follow-up. An algorithm defined treatment patterns as lines of therapy (LOTs). The Kaplan-Meier method was used to estimate overall survival for the full sample as well as by LOT, surgical resection, Charlson Comorbidity Index (CCI), tumor size, and age. Resource use and costs during the follow-up period were reported in terms of total and per-patient-per-month (PPPM) estimates. Results A total of 4308 patients with GBM were identified (median age, 74 years; CCI of 0, 52%). The most commonly used first LOT was temozolomide (82%), whereas chemotherapy + bevacizumab was most prevalent for second-line (42%) and third-line (58%) therapy. The median overall survival was 5.9 months for resected patients and 3 months for unresected patients, with considerable heterogeneity depending on patient characteristics. A great proportion of patients had claims for an ICU admission (86.2%), skilled nursing facility (76.9%), and home health (56.0%) in the postdiagnosis period. The cumulative mean cost was $95 377 per patient and $18 053 PPPM, mostly attributed to hospitalizations. Conclusions Limited treatment options, poor survival, and economic burden emphasize the need for novel interventions to improve care for Medicare patients with GBM.

Background Recent approvals of second-generation androgen receptor inhibitors (SGARIs) have changed the treatment landscape for non-metastatic castration-resistant prostate cancer (nmCRPC). These SGARIs have similar efficacy but differ in safety profiles. We used a discrete choice experiment to explore how United States physicians make treatment decisions between adverse events (AEs) and survival gains in nmCRPC, a largely asymptomatic disease. Methods Treating physicians (n = 149) participated in an online survey that included 14 treatment choice questions, each comparing 2 hypothetical treatment profiles, which varied in terms of 5 safety and 2 efficacy attributes. We described safety attributes (fatigue, skin rash, cognitive problems, falls, and fractures) in terms of severity and frequency, and efficacy attributes (overall survival [OS] and time to pain progression) in terms of duration of effect. We used a random parameters logit model to estimate preference weights and importance scores for each attribute. We also estimated the amount of survival gain physicians were willing to trade for a reduction in specific AEs between treatment options. Results Physicians placed more importance on survival than on time to pain progression, and viewed a reduction in cognitive problems from severe to none, a reduction in risk of a serious fracture from 8% to none, and a reduction in fatigue from severe to none as the most important safety attributes. Physicians were willing to forego 9.1 and 6.6 months of OS, respectively, to reduce cognitive problems and fatigue from severe to mild-to-moderate. To reduce the risk of a serious fracture from 8 to 5% and 5% to none, physicians were willing to trade 3.9 and 5.3 months of OS, respectively. Conclusions Physicians were willing to trade substantial amounts of survival to avoid AEs between hypothetical treatments. These results emphasize the importance of carefully balancing therapies’ benefits and risks to ultimately optimize the overall quality of nmCRPC patients’ survival. Nonetheless, it is noted that the results from the study sample of 149 physicans may not be representative of the viewpoints of all nmCRPC-treating physicians.

INTRODUCTION Long-acting products are changing the haemophilia A treatment landscape by giving patients and caregivers treatment options with varying product attributes. AIM A discrete choice experiment (DCE) was used to elicit treatment attribute preferences among patients with haemophilia A and caregivers of children with haemophilia A. MATERIALS & METHODS A survey of sociodemographics and preferences was completed by an online panel of adult patients with haemophilia A and caregivers of children (

Background In this analysis we compared quality-adjusted survival outcomes between nab-paclitaxel (nab-P) and standard paclitaxel (Pac) using data from the nab-P phase III registration trial in metastatic breast cancer. Patients and Methods Quality-adjusted overall survival was estimated using the quality-adjusted time without symptoms or toxicity (Q-TWiST) approach. Overall survival was partitioned into time without progression/Grade ≥ 3 adverse events (AEs) toxicity (TWiST), time with Grade ≥ 3 AE toxicity (TOX), and time after relapse (REL). Q-TWiST was calculated by multiplying mean time in each health state by its assigned utility (base-case utility values: time without symptoms of disease progression or toxicity of Grade ≥ 3 adverse events [TWiST] = 1.0, TOX = 0.5, and REL = 0.5). In threshold analyses, TOX and REL varied from 0.0 to 1.0 whereas TWiST was maintained at 1.0. Comparisons were made for the intent-to-treat population and the subset of patients initiating the study drugs as second or subsequent lines (2L+) of chemotherapy (per approved nab-P indication; 2L+ subpopulation). A ≥ 15% relative Q-TWiST gain (vs. mean Pac overall survival) was considered clearly clinically important. Results In the intent-to-treat population, nab-P (n = 229) versus Pac (n = 225) resulted in nonsignificant gains of 1.4 months of mean Q-TWiST (11.6 vs. 10.2 months; 95% confidence interval [CI], −0.03 to 2.8). In the 2L+ subpopulation, nab-P (n = 132) versus Pac (n = 136) resulted in a statistically significant gain of 2.2 months of mean Q-TWiST (10.5 vs. 8.4 months; 95% CI, 0.6-3.8), with a 17.1% relative Q-TWiST gain (threshold analysis range, 14.0%-19.5%, both figures significant). Conclusion In its approved indication for metastatic breast cancer, nab-P showed a statistically significant and clearly clinically important improvement in quality-adjusted survival time versus Pac in the 2L+ subpopulation.

Introduction Previous trials have demonstrated reductions in atopic dermatitis (AD) incidence when healthy, high-risk, non-exclusively breastfed infants were fed until four months of age with 100% whey-based partially hydrolysed formula (PHF-W) versus standard cow's milk formula (CMF). We assessed the cost-effectiveness of this intervention in Singapore. Methods Modelling techniques were used to simulate, from birth to Month 30, the incidence and clinical/economic burden of AD in high-risk, non-exclusively breastfed infants fed with PHF-W or CMF for up to four months. Epidemiologic and clinical data were from a local comparative trial. Expert opinion informed AD treatment patterns and outcomes. Outcomes included reduction in AD risk, time spent with AD, days without AD flare, quality-adjusted life years (QALYs) and direct/indirect costs. Multivariate probabilistic sensitivity analysis was used to assess model parameter uncertainty. Results Over 30 months, with the use of PHF-W instead of CMF, the proportion of children who developed AD and the time spent with AD decreased by 16.0% (28.3% vs. 44.3%) and 6.4 months, respectively, while time without AD flare and QALYs increased by 14.9 days and 0.021 QALYs per patient, respectively. Estimated AD-related discounted costs per child for PHF-W and CMF were SGD 771 and SGD 1,309, respectively (net savings: SGD 538). PHF-W was less expensive and more effective than CMF for 73%, and cost less than SGD 50,000 per QALY for 87% of all multivariate simulations. Conclusion Early short-term nutritional intervention with PHF-W instead of CMF may reduce AD incidence and costs for healthy, high-risk, non-exclusively breastfed infants in Singapore.

AIM The phase III MPACT trial (N = 861) demonstrated superior overall survival (OS) with first-line nab-paclitaxel plus gemcitabine versus gemcitabine alone (median, 8.7 months vs 6.6 months; hazard ratio [HR], 0.72; 95% confidence interval [CI], 0.62-0.83; P

Introduction: The Quality-Adjusted Time Without Symptoms or Toxicity (Q-TWiST) has been used to evaluate the clinical benefits and risks of oncology treatments. However, limited information is available to interpret and contextualize Q-TWiST results. Areas covered: A systematic review of Q-TWiST literature was conducted to provide contextualizing benchmarks for future studies. 51 articles with 81 unique Q-TWiST comparisons were identified. The mean (95% CI) and median absolute Q-TWiST gains for treatment versus control arms were 2.78 (1.82–3.73) months and 2.20 months across all cancers, respectively. The mean (median) relative Q-TWiST gains were 7.8% (7.2%) across all cancers. Most (88%) studies reported positive gains. The percentage of studies with relative Q-TWiST gains ≥10% (ie, clinically important difference) and ≥15% (ie, clearly clinically important difference) were 40.0% and 22.7%, respectively. Expert commentary: The relevance of Q-TWiST in assessing net clinical benefits of cancer therapy has not diminished, despite an arguably low number of published studies. The interest in such assessment is highlighted by the recent emergence of oncology value frameworks. The Q-TWiST should be compelling to clinicians as it integrates clinical information (ie, toxicity, relapse/progression, and survival) and patient preferences for each of these states into a single meaningful index.

Introduction This study sought to estimate the global prevalence of transthyretin familial amyloid polyneuropathy (ATTR-FAP). Methods Prevalence estimates and information supporting prevalence calculations was extracted from records yielded by reference-database searches (2005-2016), conference proceedings, and nonpeer reviewed sources. Prevalence was calculated as prevalence rate multiplied by general population size, then extrapolated to countries without prevalence estimates but with reported cases. Results Searches returned 3,006 records; 1,001 were fully assessed and 10 retained, yielding prevalence for 10 "core" countries, then extrapolated to 32 additional countries. ATTR-FAP prevalence in core countries, extrapolated countries, and globally was 3,762 (range 3639-3884), 6424 (range, 1,887-34,584), and 10,186 (range, 5,526-38,468) persons, respectively. Discussion The mid global prevalence estimate (10,186) approximates the maximum commonly accepted estimate (5,000-10,000). The upper limit (38,468) implies potentially higher prevalence. These estimates should be interpreted carefully because contributing evidence was heterogeneous and carried an overall moderate risk of bias. This highlights the requirement for increasing rare-disease epidemiological assessment and clinician awareness. Muscle Nerve 57: 829-837, 2018.

6567 Background: In CM 9ER (ClinicalTrial.gov identifier NCT03141177), N+C demonstrated significant progression-free survival gains (median: 17.0 vs. 8.3 months [mos]; hazard ratio [HR]: 0.52; P

Introduction Use of benzodiazepines to treat insomnia has been associated with serious side effects and abuse potential. Insomnia patients are at high risk of opioid abuse and better sleep patterns may help to reduce opioid use. This study examined the trend in the use of benzodiazepines and prescription opioids before and after initiation of suvorexant in insomnia patients. Methods The study analyzed 2015–2019, Optum Clinformatics Data Mart. Insomnia patients, identified using ICD-9/10 codes and prescribed suvorexant were included. The study included incident (newly diagnosed) and prevalent cohorts of insomnia patients. The proportion of patients on benzodiazepines or prescription opioids were calculated for 12 monthly intervals before (pre-period) and after initiation of suvorexant (post-period). Interrupted time series (ITS) analysis was conducted to assess trends for use of benzodiazepine or prescription opioids over time. Results A total of 5,939 patients from the incident insomnia cohort and 18,920 from the prevalent cohort were included. For the incident cohort, mean age was 64.47 (SD: 15.48), 63% were females, 71% had Medicare Advantage coverage, 59% had Charlson comorbidity index score (CCI) ≥ 1, 27% had an anxiety disorder and 16% had substance abuse disorder. Prevalent insomnia cohort was similar but had higher CCI. Results from ITS suggested that at the beginning of the pre-period, 28% of incident insomnia patients used either opioids or benzodiazepines with the rate of use in the pre-period increasing by 0.11% per month. In the post-period, the rate of use decreased by 0.33% per month. About 26% patients used benzodiazepines or opioids at 12-month after suvorexant initiation. In the absence of suvorexant, this proportion would have been 31%. Similar findings were observed for the prevalent insomnia cohort. A larger decrease was observed for opioid use than benzodiazepines. Conclusion The rate of benzodiazepines or prescription opioid use decreased over time after the initiation of suvorexant. Suvorexant has the potential to reduce the use of opioids and benzodiazepines among insomnia patients. Further research is needed to confirm these findings. Support (if any) This study was sponsored by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

This analysis assessed the direct medical costs of newly-diagnosed, temozolomide (TMZ)-treated glioblastoma (GBM) from the perspective of a US commercial setting.The analysis included subjects identified from the IMS PharMetrics LifeLink Plus™ claims database from January 1, 2008 to August 31, 2014 who were ≥18 years of age, had ≥1 malignant brain cancer diagnosis, had brain surgery ≤90 days prior to TMZ initiation, had TMZ treatment, and were continuously enrolled for ≥12 months pre-diagnosis and ≥1 month post-diagnosis. Per-patient per-month (PPPM) and cumulative costs from 3 months pre-diagnosis to various post-diagnosis follow-up time points were calculated. Multivariable analyses were used to estimate adjusted mean cost and identify contributors of cost.The study included 2,921 subjects (median age = 56 years; 60% male). After diagnosis, the median (interquartile range, IQR) number of inpatient, emergency department, and outpatient visits were 2 (1-4), 1 (1-3), and 19 (13-27); median (IQR) length of stay per hospitalization was 5 (3-9) days. Mean total cumulative costs per patient from 3 months pre-diagnosis to 12 months and to 5 years post-diagnosis were $201,749 (197,490-206,024) and $268,031 (262,877-274,416). Mean (SD) PPPM costs were $818 (1,128) and $7,394 (8,676) pre- and post-GBM diagnosis, respectively. The variables most predictive of cumulative costs included radiation therapy (+$81,732), ≥2 weeks of hospitalization (+$49,629), and ≥7 MRI scans (+$40,105).The direct medical costs of newly-diagnosed, TMZ-treated GBM in commercially insured patients are substantial, with estimated total cumulative costs of $268,031.

Background: In the NAPOLI-1 Phase 3 trial, nal-IRI+5-fluorouracil and leucovorin (5-FU/LV) significantly improved median overall survival (6.1 vs 4.2 months, P=0.012) and progression-free survival (3.1 vs 1.5 months, P=0.0001) vs 5-FU/LV alone in metastatic pancreatic adenocarcinoma patients previously treated with gemcitabine-based therapy. This analysis evaluated between treatment differences in quality-adjusted time without symptoms of disease progression or toxicity (Q-TWiST). Methods: Overall survival was partitioned into time with grade ⩾3 toxicity (TOX), disease progression (REL), and time without disease progression symptoms or grade ⩾3 toxicity (TWiST). Mean Q-TWiST was calculated by weighting time spent by a utility of 1.0 for TWiST and 0.5 for TOX and REL. In threshold analyses, utility for TOX and REL were varied from 0.0 to 1.0. Results: Patients in nal-IRI+5-FU/LV (n=117) vs 5-FU/LV (n=119) had significantly more mean time in TWiST (3.4 vs 2.4 months) and TOX (1.0 vs 0.3 months) but similar REL (2.5 vs 2.7 months). In the base case, nal-IRI+5-FU/LV patients had 1.3 months (95% CI, 0.4–2.1; 5.1 vs 3.9) greater Q-TWiST (threshold analyses range: 0.9–1.6 months). Conclusions: Within NAPOLI-1, nal-IRI+5-FU/LV resulted in statistically significant and clinically meaningful gains in quality-adjusted survival vs 5-FU/LV alone.

Background: Limited information is available about treatment patterns for elderly patients (pts) with metastatic triple negative breast cancer (mTNBC). This analysis characterized real-world drug utilization patterns and associated overall survival (OS) for Medicare mTNBC pts. Methods: Pts ≥66 years of age who were newly diagnosed with mTNBC between 2004 and 2011 were identified from the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database. Triple negative status was obtained from the SEER registry, except for HER2 that was unavailable from 2004-2009 during which we assumed that pts who had a claim for a HER2 test followed by absence of hormonal therapy to be presumed HER2 negative. Pts were followed from diagnosis to death, Medicare disenrollment, HMO enrollment, or 12/31/2013 (whichever occurred first) to characterize the sequence of chemotherapy received – first regimen (1R), second regimen (2R), and third regimen (3R) and median (interquartile, IQR) duration of and between regimens. OS estimates were reported using the Kaplan-Meier method. Results: Among 694 mTNBC pts, 69 died within 30 days of diagnosis and were excluded. In the remaining 625 pts observed from 2004 through 2013 (median age: 75 years; Charlson comorbidity index (CCI) ≥2: 21%; and median follow-up: 11.4 months), 317 (51%) received chemotherapy. Of the 317 pts, 161 got only 1R, 88 got only 2R, and 68 got 3R+. Compared to pts on 1R, pts on 2R were significantly younger (median age: 2R, 72; 1R, 75 years), married (2R, 40%; 1R, 30%), had fewer comorbidities (CCI≥2: 2R, 16%; 1R, 23%). The top 2 most commonly prescribed single agents in 1R, 2R, and 3R were: 1R, paclitaxel followed by capecitabine; 2R, capecitabine followed by paclitaxel; 3R, gemcitabine followed by capecitabine. The most common combination regimen given was taxane-based in 1R (57%) and 2R (70%). Drug utilization patterns First Regimen (n=317)Second Regimen (n=156)Third Regimen (n=68)Single Agent205 (65%)74 (47%)40 (59%)Microtubule inhibitors80 (39%)23 (31%)NRPaclitaxel72 (35%)18 (24%)NRAnthracyclines29 (14%)13 (18%)NRDoxorubicin27 (13%)13 (18%)NRAntimetabolites/Others96 (47%)38 (51%)27 (73%)Capecitabine51 (25%)20 (27%)NRGemcitabineNRNR13 (35%)OthersNRNRNRCombination Regimens112 (35%)82 (53%)28 (41%)Taxane-based64 (57%)57 (70%)NRNR, not reported per DUA with NCI. %, col. % relative to single/comb. category Median (IQR) durations of 1R, 2R, and 3R were 2.7 (1.4-4.4), 3.1 (1.6-5.0), and 2.3 (0.9-4.5) months, respectively. Median time from diagnosis to start of 1R was 1.6 (0.9-2.8) months. Median time to start of 2R and 3R after the end of the previous regimen was 4.6 (2.1-8.1), and 6.2 (3.3-11.0) months, respectively. The median (12-month) OS was 7 months (34%) for all pts and ranged from 3.5 (17%) in the untreated to 25.3 (88%) months in 3R+ pts. Conclusions: About half of Medicare mTNBC pts do not receive chemotherapy in the real world. Paclitaxel and capecitabine were the most commonly used single agents and taxane-based combination therapy was the most commonly used combination. Citation Format: Aly A, Shah R, Hill K, Waldeck AR, Botteman M. United States real-world drug utilization patterns and associated overall survival in Medicare patients with newly-diagnosed metastatic triple negative breast cancer using surveillance, epidemiology, and end results-Medicare data [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P6-08-05.

Background: Chemotherapy-induced nausea and vomiting (CINV) are among the most common and debilitating side-effects patients experience during chemotherapy, and are associated with consider...

AIMS: Medicare patients with metastatic or surgically unresectable urothelial carcinoma (mUC) often receive platinum-based chemotherapy as first line of therapy (LOT) but invariably progress, requiring additional LOTs and healthcare resource use (HCRU). To better understand the evolving mUC treatment landscape, we estimated the economic burden of chemotherapy-based mUC treatments among US Medicare patients. METHODS: Newly diagnosed Medicare patients with mUC were identified from the Surveillance, Epidemiology, and End Results (SEER)-Medicare database. Patients were followed from diagnosis to death, disenrollment, or end of study to characterize LOTs (first [LOT1], second [LOT2], and third+ [LOT3+]). Kaplan-Meier methods were used to estimate overall survival (OS) by LOT. HCRU and mean costs were reported over the follow-up period, LOT duration, or maximum LOT received. RESULTS: Among 1,873 eligible patients with mUC (median age, 77 years; median follow-up, 7.5 months), 1,035 (55%) received no chemotherapy. Among chemotherapy-treated patients, 61% had LOT1 only, 25% had LOT1 and LOT2 only, and 14% had ≥3 LOTs. Median OS was 8.1 months, range 4.3 (untreated) to 29.8 (LOT3+) months. HCRU frequency increased with additional LOTs. Mean cumulative per-patient cost was $82,912 for all patients, increasing with additional LOTs (untreated, $57,207; LOT1, $99,213; LOT2, $125,190; LOT3+, $163,884). Mean per-patient per-month cost was $18,827 for all patients, decreasing with increasing number of LOTs received (untreated, $27,211; LOT1, $9,601; LOT2, $7,325; LOT3+, $6,017). LIMITATIONS: Potential for treatment misclassification when using the algorithm defining LOTs and non-generalizability of results to younger patients. CONCLUSIONS: Over 50% of Medicare patients with mUC received no chemotherapy. Among chemotherapy-treated patients, most received only one LOT. Additional LOTs led to higher mean costs and HCRU, but as patients were followed longer, monthly costs decreased. As treatments evolve to include immuno-oncology agents, these findings provide a clinically relevant economic benchmark for mUC treatment across different traditional LOTs.

This study assessed the net health benefits of treatment with nivolumab versus everolimus among patients with advanced renal cell carcinoma by assessing the quality (ie, patient preferences) and quantity of survival (ie, time spent with significant toxicities, in progression, or before progression and without significant toxicities). Nivolumab resulted in a 3.3-month quality-adjusted survival gain versus everolimus that was statistically significant and clearly clinically meaningful. Background: This analysis compared quality-adjusted time without symptoms of disease progression or toxicity (Q-TWiST) between nivolumab and everolimus among previously treated patients with advanced renal cell carcinoma enrolled in the phase III CheckMate 025 trial (NCT01668784). Materials and Methods: At 45-month follow-up, overall survival (OS) was partitioned into 3 health states: TWiST, time with grade ≥ 3 toxicity (TOX), and time after progression (REL). Mean Q-TWiST was determined by multiplying each state’s duration with its utility (TWiST, 1.0; TOX, 0.5; REL, 0.5). Relative Q-TWiST gains (calculated as Q-TWiST difference divided by everolimus OS) of ≥ 10% were predefined as clinically important. Immuno-oncology-specific sensitivity analyses considered 4 alternative progression definitions: Tumor size increase ≥ 25% from nadir; treatment discontinuation; ≥ 2-point reduction from baseline in Functional Assessment of Cancer Therapy-Kidney Symptom Index Disease-Related Symptoms scores; and a composite definition. A scenario incorporating grade ≥ 2 toxicities was tested. Results: Compared with everolimus, nivolumab was associated with a significant Q-TWiST improvement of 3.3 months (P < .001). In all sensitivity analyses, nivolumab was associated with Q-TWiST gains (relative gain %) ranging from 3.3 months (14.4%) to 4.8 months (20.9%). Conclusions: Nivolumab is associated with a statistically significant and clinically meaningful gain in quality-adjusted OS versus everolimus among previously treated patients with advanced renal cell carcinoma.

To compare the quality-adjusted survival of nivolumab plus ipilimumab combination and nivolumab alone versus ipilimumab alone among treatment-naive patients with advanced melanoma based on a minimum 36-month follow-up from the CheckMate 067 trial. Overall survival was partitioned into time without symptoms of progression or toxicity (TWiST), time with treatment-related grade ≥ 3 adverse events after randomization but before progression (TOX), and time from progression until end of follow-up or death (REL). Mean quality-adjusted TWiST (Q-TWiST) was calculated by multiplying the mean time spent in each health state by a utility of 1.0 for TWiST and 0.5 for TOX and REL. Sensitivity analyses included varying utilities of TOX and REL; Q-TWiST gains at different follow-up times were calculated using EQ-5D-3L utilities from the trial. Relative Q-TWiST gain of ≥ 10% was considered clinically important. Compared with ipilimumab-treated patients, those who received nivolumab + ipilimumab combination had significantly longer TWiST and TOX but shorter REL; nivolumab-treated patients had significantly longer TWiST, shorter REL, and shorter but statistically nonsignificant TOX. Mean Q-TWiST was highest for nivolumab + ipilimumab (23.5 months; 95% CI 21.9–25.2), followed by nivolumab (21.8 months; 95% CI 20.2–23.4) and ipilimumab (15.3 months; 95% CI 13.9–16.6). Relative Q-TWiST gains were favorable and clinically important for nivolumab + ipilimumab combination (+ 36.81%) and nivolumab alone (+ 29.18%) versus ipilimumab alone. Relative gains increased with follow-up from 3 to 40 months for all comparisons. These gains remained consistent in magnitude and direction in the different sensitivity analyses. Nivolumab + ipilimumab combination and nivolumab alone resulted in a statistically significant and clinically important improvement in quality-adjusted survival compared with ipilimumab alone.

Introduction: R/R FLT3-ITD AML is an aggressive hematologic malignancy with a generally poor prognosis and high relapse rate even after allogeneic hematopoietic stem cell transplantation (HSCT). QuANTUM-R (NCT02039726), a large, global, phase 3, randomized, controlled trial, showed that single-agent quizartinib significantly prolonged overall survival (OS) vs salvage chemotherapy (SC) in patients with R/R FLT3-ITD AML after first-line treatment with or without HSCT (Cortes et al, Lancet Oncol 2019). To evaluate both quality and quantity of life for patients with R/R FLT3-ITD AML, we conducted a Q-TWiST analysis of QuANTUM-R data to compare survival between patients receiving quizartinib and SC adjusted for quality of life (QOL). Methods: The primary analysis cohort was the intent-to-treat (ITT) QuANTUM-R population, which included 367 patients (245 patients receiving quizartinib; 122 patients receiving SC). The secondary analysis cohort was the per-protocol analysis set (PPS), which excluded patients randomized but not treated and patients with major protocol violations who would affect assessment of efficacy endpoints (231 patients receiving quizartinib; 88 patients receiving SC). Each patient's OS was partitioned into 3 health states: time with any grade 3/4 treatment-emergent adverse events (TEAEs) before relapse (TOX), time without relapse or grade 3/4 toxicity (TWiST), and time after relapse (REL). Q-TWiST was assessed at 104 weeks (approximate median follow-up of QuANTUM-R) as the mean time spent in each state weighted by its respective QOL, represented by health utility (u; 0.0-1.0). Q-TWiST was calculated as follows: Q-TWiST = u(TWiST) × TWiST + u(TOX) × TOX + u(REL) × REL for which u(TWiST), u(TOX), and u(REL) represent the utilities applied to the restricted mean time in TWiST, TOX, and REL, respectively. Relative Q-TWiST gain (ie, Q-TWIST gain divided by mean OS of salvage chemotherapy) of ≥ 15% was considered clinically important, based on published minimally important difference norms (Revicki et al, Qual Life Res 2006). The base case that assessed the Q-TWiST difference between quizartinib and SC for the ITT population included any grade 3/4 TEAEs and set utilities at commonly assumed values: u(REL) = u(TOX) = 0.5, relative to u(TWiST) = 1.0. A sensitivity analysis was conducted for which u(TOX) and u(REL) were varied from 0.0 to 1.0. The following additional scenarios analyses were conducted: (1) including only treatment-related (TR) grade 3/4 TEAEs, (2) assessing Q-TWiST difference between quizartinib and SC for the PPS cohort, and (3) including only TR grade 3/4 TEAEs for the PPS cohort. 95% CIs were estimated via nonparametric bootstrap. Results: For the ITT population, quizartinib was associated with a mean OS gain of 8.5 weeks vs SC at 104 weeks from randomization (Table). In base case, the mean (95% CI) Q-TWiST gain at 104 weeks for quizartinib vs SC was 6.7 weeks (1.7-12.3; relative gain, 20.3%), which was statistically significant and clinically meaningful (Table). For the sensitivity analysis for which u(TOX) and u(REL) were varied from 0.0 to 1.0, Q-TWiST gains for quizartinib ranged from 5.0 (u[REL] = u[TOX] = 0.0) to 8.5 weeks (u[REL] = u[TOX] = 1.0). The relative Q-TWiST gains for quizartinib vs SC remained clinically important, irrespective of the values for u(TOX) and u(REL) and ranged from 15.2% to 25.5% (Figure). In the scenario analyses (Table), (1) when only TR grade 3/4 TEAEs were included, the Q-TWiST gain for quizartinib was 7.4 weeks (2.2-13.0; relative gain, 22.5%), (2) in the PPS cohort, the mean (95 % CI) Q-TWiST gain for quizartinib was 6.9 weeks (0.8-13.5; relative gain, 20.7%), and (3) when including only TR grade 3/4 TEAEs in the PPS, the Q-TWiST gain for quizartinib was 7.5 weeks (1.5-14.2; relative gain, 22.5%). Conclusions: Quizartinib significantly prolonged quality-adjusted survival vs SC in patients with R/R FLT3-ITD AML after disease control, safety, and QOL were accounted for, providing evidence of meaningful clinical benefit in a patient population with few treatment options. To put these results in perspective, the relative Q-TWiST gains for quizartinib reported herein are larger than nearly 90% of the relative Q-TWiST gains reported in a recent systematic review of 81 Q-TWiST comparisons across 13 cancers (Solem et al, Exp Rev Pharmacoecon Outcomes Res 2018). Disclosures Cortes: Astellas Pharma: Consultancy, Honoraria, Research Funding; Jazz Pharmaceuticals: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Takeda: Consultancy, Research Funding; Pfizer: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding; Daiichi Sankyo: Consultancy, Honoraria, Research Funding; Merus: Consultancy, Honoraria, Research Funding; Immunogen: Consultancy, Honoraria, Research Funding; Forma Therapeutics: Consultancy, Honoraria, Research Funding; Biopath Holdings: Consultancy, Honoraria; BiolineRx: Consultancy; Sun Pharma: Research Funding. Ganguly:Daiichi Sankyo: Research Funding; Kite Pharma: Honoraria, Other: Advisory Board; Janssen: Honoraria, Other: Advisory Board; Seattle Genetics: Speakers Bureau. Khaled:Omeros: Consultancy; Alexion: Consultancy, Speakers Bureau; Daiichi Sankyo: Other: Travel support. Krämer:Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Daiichi-Sankyo: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bayer: Research Funding; BMS: Research Funding. Levis:Daiichi Sankyo Inc: Consultancy, Honoraria; Agios: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Menarini: Consultancy, Honoraria; Novartis: Consultancy, Research Funding; Astellas: Consultancy, Research Funding; FUJIFILM: Consultancy, Research Funding. Martinelli:Janssen: Consultancy, Other: trial grant; Celgene: Consultancy, Honoraria, Other: trial grant; Abbvie: Consultancy, Honoraria, Other: trial grant; Pfizer: Consultancy, Other: trial grant; Roche: Consultancy, Other: trial grant; Incyte: Consultancy, Other: trial grant; Daiichi Sankyo: Consultancy, Honoraria; Amgen: Consultancy, Other: trial grant; Novartis: Consultancy, Other: trial grant; Ariad: Consultancy, Other: trial grant. Perl:Bayer: Research Funding; BioMed Valley Discoveries: Research Funding; FujiFilm: Research Funding; Novartis: Honoraria, Other: Advisory board, Non-financial support included travel costs for advisory board meetings as well as a medical writing company that assisted with manuscript preparation/submission and slide deck assembly for academic meeting presentations of the data., Research Funding; Jazz: Consultancy, Honoraria, Other: Non-financial support included travel costs for advisory board meetings.; AbbVie: Consultancy, Honoraria, Other: Non-financial support included travel costs for advisory board meetings.; Actinium Pharmaceuticals: Consultancy, Honoraria, Other: Clinical Advisory Board member, Research Funding; Agios: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Non-financial support included travel costs for advisory board meetings.; Daiichi Sankyo: Consultancy, Honoraria, Other, Research Funding; Arog: Consultancy, Other: Non-financial support included travel costs for advisory board meetings.; Astellas: Consultancy, Honoraria, Other: Non-financial support included travel costs for advisory board meetings as well as a medical writing company that assisted with manuscript preparation/submission and slide deck assembly for academic meeting presentations of trial data., Research Funding; NewLink Genetics: Consultancy, Honoraria, Other: Non-financial support included travel costs for advisory board meetings.; Takeda: Consultancy, Honoraria, Other: Non-financial support included travel costs for advisory board meetings.. Russell:Astellas: Consultancy, Honoraria, Speakers Bureau; Jazz: Consultancy, Honoraria, Speakers Bureau; DSI: Consultancy, Honoraria, Speakers Bureau; Pfizer Inc: Consultancy, Honoraria, Speakers Bureau. Botteman:Pharmerit International: Employment, Equity Ownership; Alnylam Pharmaceuticals: Consultancy; Daiichi Sankyo: Consultancy, Research Funding. Shah:Merck: Research Funding; Bayer: Research Funding; Pfizer: Research Funding. Luo:Pharmerit International: Employment. Shun:Daiichi Sankyo: Employment. Ray:Daiichi Sankyo: Employment, Equity Ownership.

Introduction: The treatment landscape for hemophilia A has evolved since the introduction of extended half-life (EHL) factor/non-factor VIII products, which allows for treatment personalization as per individual need, such as a less frequent infusion schedule and increased protection. Many different treatment attributes (e.g. safety, efficacy, and treatment burden) can influence patients' and caregivers' decisions in their choice of treatment. We used a discrete choice experiment (DCE) to elicit preferences from hemophilia A patients and caregivers for the treatment attributes of new EHL/non-factor products. Methods: Adult patients and caregivers providing care for a young patient ( Results: 113 patients (mean age: 35.5 years) and 96 caregivers (mean age of the child they cared for: 10.3 years) were included in the analysis. Among them, 88 patients (77.9%) self-reported having severe hemophilia while 81 (84.4%) caregivers reported that the child (6 years vs. Conclusions: Besides safety, other attributes of products such as bleed protection and reducing dosing frequency had an important influence on hemophilia A patients' and caregivers' treatment choices in the DCE survey. The importance that patients and caregivers placed on these attributes also depended on the extent of bleed protection improvement or dosing reduction. Adult patients and caregivers making treatment decisions for their young patients may value dosing and safety of treatments differently. With more treatment options becoming available for people with hemophilia, it is important that patients and caregivers are well-informed about the comprehensive benefit-risk profile of different products to make the most optimal decisions to improve their current treatment and outcomes. Figure Disclosures Joshi: Pharmerit International: Employment. Ng:Pharmerit International: Employment. Botteman:Alnylam Pharmaceuticals: Consultancy; Pharmerit International: Employment, Equity Ownership; Daiichi Sankyo: Consultancy, Research Funding. Li:Bioverativ, a Sanofi Company: Employment. Shah:Pharmerit International: Employment. Jain:Sanofi Genzyme: Employment, Equity Ownership. Lyn:Sanofi Genzyme: Employment. Su:Sanofi Genzyme: Employment, Equity Ownership.

Hereditary transthyretin (TTR) amyloidosis with polyneuropathy (hATTR-PN) is a rare, autosomal dominant amyloidosis characterized primarily by progressive ascending sensorimotor neuropathy often associated with autonomic involvement. hATTR-PN is caused by a mutation in the TTR gene leading to protein misfolding and amyloid accumulation in peripheral nerves and vital organs. The latest global prevalence estimates point to 10,000 cases worldwide, with an upper end of about 40,000. Tafamidis has been approved in over 40 countries for delaying neurologic disease progression in early-stage hATTR-PN. Multiple observational studies have examined clinical outcomes in hATTR-PN patients treated with tafamidis in the routine clinical setting. Integrative data analysis (IDA) is a technique for optimally constructing synthetic treatment and control cohorts from multiple independent studies, which allows meta-analysis of patient-level data. Herein, we provide a proof of concept for the application of IDA to real-world and natural history hATTR-PN data. IDA permits increased understanding of outcomes in tafamidis-treated and untreated persons with hATTR-PN by optimally pooling all available information. Summary statistics corresponding to the Neuropathy Impairment Score-Lower Limb (NIS-LL) from five published studies were pooled, converted to change from baseline means and variances, and analyzed using IDA. IDA-based synthetic cohorts were generated by averaging across studies stratified on treatment versus control cohort. Trends in change from baseline in each study and the corresponding synthetic cohorts were plotted. Patient-level data were simulated from the synthetic cohort trends in a Monte Carlo simulation to highlight the ability to contrast synthetic cohort trends using the mixed model for repeated measures (MMRM). The average sample size among the five studies was 71 (37–128) patients. The average NIS-LL trends indicated that tafamidis-treated patients experienced slower progression in neuropathy compared to untreated patients. Synthetic cohort trends reflected the trends observed in the contributing studies, while simultaneously shrinking the width of corresponding confidence bands. Monte Carlo simulation results demonstrated precise recovery of the synthetic cohort and time-dependent simulated NIS-LL means by the MMRM. This proof of concept demonstrates the utility of IDA-based synthetic cohorts for increased precision in characterizing and testing hypotheses about treatment outcomes and prognosis in hATTR-PN. Pfizer. Plain language summary available for this article. Hereditary transthyretin (TTR) amyloidosis with polyneuropathy (hATTR-PN) is a rare inherited disease. It is caused by genetic mutations that change the structure of TTR proteins, causing an abnormal buildup of amyloid protein deposits (amyloidosis) in your body’s nerves and organs. This damages your nerves and organs and causes weakness, numbness, and pain. The drug tafamidis stabilizes TTR proteins and slows the disease’s progression. Tafamidis has been approved in over 40 countries based on clinical trial results. However, researchers and doctors are still studying how it works for patients in the real world. Over the past few years, researchers have published multiple real-world studies about tafamidis, but it is difficult to get a full, uniform picture of how well tafamidis works, because the studies are too different. hATTR-PN is a rare disease, so the number of patients per study is small; small sample sizes can make it more difficult to tell true effects from statistical noise, whereas large samples can be more precise. Integrative data analysis (IDA) is a technique that allows researchers to combine the results of multiple studies into a large pool of data and analyze the larger data set (or “synthetic cohort”) instead. This makes optimal use of each study’s information and creates a fuller picture of the treatment’s real-world results. This manuscript is a “proof of concept” to demonstrate how the IDA statistical method can be used to build synthetic cohorts from real-world hATTR-PN data, improving our understanding of hATTR-PN patients’ outcomes.

Background: This analysis compared the quality-adjusted survival and clinical outcomes of albumin-bound paclitaxel+carboplatin (nab-PC) vs solvent-based paclitaxel+carboplatin (sb-PC) as first-line therapy in advanced non-small-cell lung cancer (NSCLC) in older patients. Methods: Using age-based subgroup data from a randomised Phase-3 clinical trial, nab-PC and sb-PC were compared with respect to overall response rate (ORR), overall survival (OS), progression-free survival (PFS), quality of life (QoL), safety/toxicity, and quality-adjusted time without symptoms or toxicity (Q-TWiST) with ages ⩾60 and ⩾70 years as cut points. Results: Among patients aged ⩾60 years (N=546), nab-PC (N=265) significantly increased ORR and prolonged OS, despite a non-significant improvement in PFS, vs sb-PC (N=281). Nab-PC improved QoL and was associated with less neuropathy, arthralgia, and myalgia but resulted in more anaemia and thrombocytopenia. Nab-PC yielded significant Q-TWiST benefits (11.1 vs 9.8 months; 95% CI of gain: 0.2–2.6), with a relative Q-TWiST gain of 10.8% (ranging from 6.4% to 15.1% in threshold analysis). In the ⩾70 years age group, nab-PC showed similar, but non-significant, ORR, PFS, and Q-TWiST benefits and significantly improved OS and QoL. Conclusion: Nab-PC as first-line therapy in older patients with advanced NSCLC increased ORR, OS, and QoL and resulted in quality-adjusted survival gains compared with standard sb-PC.

Background: To describe healthcare costs, excluding ipilimumab drug costs, in patients with advanced melanoma receiving ipilimumab in the US community practice setting. Methods: This was a retrospective chart review of unresectable stage III/IV melanoma patients who received first-line ipilimumab monotherapy between 04/2011 and 09/2012. Healthcare resource utilization included inpatient, emergency, specialist and hospice visits, laboratory tests, radiation, surgeries, and nursing home stays. Publicly available US unit costs were applied to each resource type to estimate costs, which were analyzed by time periods: during ipilimumab treatment, post-ipilimumab treatment (post-regimen), and within 90 days prior to death (pre-death). Generalized linear mixed models were used to explore cost predictors during the treatment period, on a per-dose-interval basis, defined as the time between ipilimumab doses. Results: Data were abstracted from 273 patient charts at 34 sites. Excluding ipilimumab drug costs, total monthly costs during the treatment regimen, post-regimen, and pre-death periods were $690, $2151, and $5123, respectively. Total healthcare costs were 27 times higher during dose intervals with a grade 3/4 adverse event compared with intervals without a grade 3/4 adverse event. Eastern Cooperative Oncology Group performance status ≥ 2 (vs 0) was also associated with significantly higher cost per dose interval. Conclusions: In this population, monthly costs exclusive of drug were significantly lower during the treatment period than in subsequent periods. Unfavorable ECOG PS was associated with significant increases in cost per dose interval. Grade 3/4 adverse events were associated with a marked increase in healthcare costs, but occurred in a small proportion of dose intervals.

Transthyretin hereditary (familial) amyloid polyneuropathy (TTR-FAP) was first identified in Portugal in 1952 [1]. In 1984, the first report of a causative mutation – substitution of methionine for...

ObjectiveTo estimate, from a Filipino societal perspective, the cost-effectiveness of preventing atopic dermatitis (AD) via early nutritional intervention with 100% whey-based partially hydrolyzed formula (PHF-W) versus standard cow’s milk formula (SF) in healthy, urban infants with atopic heredity who are not exclusively breast-fed.MethodsA Markov model was used to simulate over 6 years the incidence of AD, days with AD symptoms, quality-adjusted life-years (QALYs), and AD-related direct and indirect (i.e., parents’/caregivers’ productivity loss) costs incurred by hypothetical cohorts of healthy, at-risk infants fed with either PHF-W or SF as AD prevention for ≤ 17 weeks. Efficacy estimates of PHF-W versus SF in preventing AD were literature-based. The resources used to manage AD (by severity, age, and treatment modality) were estimated using clinical pathways derived from clinical expert opinion. Local costs were applied to resource use. Results were presented as point estimates and as 95 percent credible intervals (CIs, i.e., range of values around the point estimate that include 95% of model simulations) generated via multivariate probabilistic sensitivity analysis using Monte-Carlo simulation techniques. All costs are reported in Philippines pesos (₱, where ₱1000 = US $22.24). All reported outcomes were discounted at a rate of 3.5% per year.ResultsBased on the 6-year simulation, compared with SF, PHF-W was predicted to result in a 14-percentage point reduction (i.e., 39% vs. 25%) (95% CI 0.09–0.19) in the incidence of AD and a gain of 0.03 (i.e., 5.46 vs. 5.43) (95% CI 0.01–0.07) QALYs/patient. PHF-W’s higher feeding formula cost (+₱1,304/patient) (95% CI −₱3,090 to ₱5,779) were offset by reductions in AD-related costs (−₱11,959/patient; i.e., ₱27,228 vs. ₱15,269) (95% CI −₱14,685 to −₱7,284), including, in particular, the costs of pharmacotherapy, formula used as treatment, and visits to physicians. As a result, PHF-W became a net cost-saving strategy within 38 weeks. Overall, PHF-W resulted in net savings of −₱10,654 (−US $237) (CI −₱4,240 [−US $94] to −₱14,544 [−US $323]) (i.e., ₱27,228 [US $606] vs. ₱16,574 [US $369]). Sensitivity analysis confirmed the robustness of results; the most influential variable was the first-year risk reduction in AD.ConclusionsBased on the present modeling exercise, compared with SF, PHF-W appears to substantially reduce the risk of AD and its associated direct and indirect medical costs in healthy, at-risk urban Filipino infants over a 6-year period.

SUMMARY Objective: To estimate the relative efficacy of pharmacological therapies for the treatment of postherpetic neuralgia (PHN), multiple sclerosis (MS)-related pain, posttraumatic pain, central poststroke pain (CPSP) and human immunodeficiency virus (HIV)-related neuropathic pain (NeP). Methods: This systematic review (through June 2011) identified randomised, controlled trials of treatments for these conditions. Bayesian mixed treatment comparison (MTC) methods were used to determine the relative efficacy and safety among the treatments within each pain condition. Results: Fifty studies were identified: 33 PHN, 2 MS-related pain, 3 CPSP, 3 posttraumatic pain and 9 HIV-related NeP. Data from 28 PHN studies including 21 interventions and 4317 patients were included into the PHN MTC. Of treatments studied in ≥ 50 patients, opioids had the greatest mean pain reduction of 1.70 vs. placebo on an 11-point numeric rating scale. Pregabalin ≥ 300 mg/ day was most effective for ≥ 30% and ≥ 50% pain reduction [relative risk (RR) vs. placebo = 2.44 and 2.13, respectively]. Data identified for MS-related pain, CPSP, posttraumatic pain and HIV-related NeP were sparse; only 7 of 17 studies had ≥ 50 patients. Adverse events (AEs) and discontinuations for most treatments were not significantly greater than placebo except in PHN, where 8 of 12 treatments had higher risks of AEs compared with placebo and tricyclic antidepressants and opioids had higher risk of discontinuation compared with placebo. Conclusions: Guideline-recommended treatments for PHN were more effective than placebo on the pain NRS and for ≥ 30% and ≥ 50% pain reduction. Although guidelines exist for the management of less common NeP conditions, little published evidence supports them. These results highlight the need for additional evaluations and more complete reporting of outcomes to help guide physicians’ treatment selections. Review criteria How did you gather, select and analyse the information you considered in your review? A search of six literature databases was conducted using prespecified search terms to identify randomised, controlled clinical trials of treatments for specific NeP conditions. Studies meeting prespecified inclusion criteria (minimum trial duration, NeP condition of interest, pharmacological treatment, etc.) were included in the study/analysis.

Catheter-related bloodstream infections (BSIs) are a serious problem leading to increased morbidity, longer hospital stay, and hence, additional costs. This study evaluated the risk of BSI and the cost of parenteral nutrition (PN) in Germany.A retrospective observational chart review of patients hospitalized from October 2009 to April 2011 and receiving PN via ready-to-use three-chamber bag (MCB), single bottle (SB) or hospital compounded admixture (CPN) was conducted across Germany. Propensity score-adjusted models were used to evaluate the association between the type of PN, BSI (Cox Proportional Hazards) and hospitalization cost (generalized linear models) within a subgroup receiving all three macronutrients (lipids, amino acids, glucose).Of the 1995 patient records reviewed (MCB=816; CPN=584; SB=595), 1457 patients received all three macronutrients. After adjustment, SB was associated with an increased hazard of BSI, vs MCB without additions (hazard ratio (HR) (95% confidence interval (CI))=2.53 (1.66-3.86)) in the total cohort. Adding supplements to MCB on the ward also increased the BSI risk in both total and subgroup analyses. In patients receiving all three macronutrients, adjusted total costs were MCB (no additions): \[euro]6,572 (95% CI: \[euro]6,896-6263); CPN: \[euro]6,869 (\[euro]7,283-6479); SB: \[euro]6,872 (\[euro]7,242-6521); MCB (ward additions): \[euro]7,402 (\[euro]7,878-6955); P0.001; P0.001.Use of MCB does not appear to increase treatment costs, possibly by reducing the risk of infection. This study identified several PN preparation methods associated with a significantly increased hazard for BSI; definitive CPN findings are limited by our inability to distinguish automated from manual pharmacy compounding.

Economic evaluation conducted in terms of cost per quality-adjusted life-year (QALY) provides information that decision makers find useful in many parts of the world. Ideally, clinical studies designed to assess the effectiveness of health technologies would include outcome measures that are directly linked to health utility to calculate QALYs. Often this does not happen, and even when it does, clinical studies may be insufficient for a cost-utility assessment. Mapping can solve this problem. It uses an additional data set to estimate the relationship between outcomes measured in clinical studies and health utility. This bridges the evidence gap between available evidence on the effect of a health technology in one metric and the requirement for decision makers to express it in a different one (QALYs). In 2014, ISPOR established a Good Practices for Outcome Research Task Force for mapping studies. This task force report provides recommendations to analysts undertaking mapping studies, those that use the results in cost-utility analysis, and those that need to critically review such studies. The recommendations cover all areas of mapping practice: the selection of data sets for the mapping estimation, model selection and performance assessment, reporting standards, and the use of results including the appropriate reflection of variability and uncertainty. This report is unique because it takes an international perspective, is comprehensive in its coverage of the aspects of mapping practice, and reflects the current state of the art. Keywords: economic evaluation, health utility, mapping, quality of life.

Background The recent approval of second-generation androgen receptor inhibitors (ARis, eg, abiraterone, enzalutamide) is anticipated to change the non-metastatic castration resistant prostate cancer (nmCRPC) treatment landscape. Herein, we describe patient (pt) and physician characteristics and historical treatment patterns as a baseline to an evolving nmCRPC treatment landscape in Japan. Methods Descriptive analyses were conducted using 2015-2017 Ipsos Global Oncology Monitor Database. Results 1,114 nmCRPC pts (median age: 80 years; median BMI: 23.1 Kg/m2; ECOG score ≤ 1: 88.8%) were included. Almost all (98.7%) pts were treated by urologists, 40.8% were stage III at initial diagnosis, and 54.5% had Gleason score between 8-10. The two most common hormone sensitive treatments which pts received preceding CRPC diagnosis were bicalutamide/leuprolide combination (42.4%) and bicalutamide/goserelin combination (16.7%). The two most commonly prescribed treatments by 1st, 2nd, and 3rd nmCRPC regimen (R) were: 1R, bicalutamide/leuprolide combination (14.4%) and leuprolide (12.7%); 2R, bicalutamide/leuprolide combination (9.4%) and flutamide/leuprolide combination (7.7%); 3R, flutamide/leuprolide combination (8.4%) and estramustine/leuprolide combination (5.5%). The proportion of pts receiving abiraterone and enzalutamide were relatively low: 66 (5.9%) and 249 (22.4%) overall; 25 (2.2%) and 120 (10.8%) in 1R; 24 (4.1%) and 79 (13.5%) in 2R; and 17 (6.2%) and 52 (19.0%) in 3R. Most common treatment discontinuation reasons were treatment resistance, progression, and side effects. Conclusions These data represent real-world treatment patterns in nmCRPC and may be reflective of a reticence to introduce pharmacotherapy in a largely asymptomatic disease. Future studies should evaluate utilization patterns after more experience with second generation ARis has accumulated and explore any putative relationship between tolerable pharmacotherapy and extent of utilization.

196 Background: Second-generation androgen receptor inhibitors (SGARIs) have been recently approved for the management of nmCRPC based on documented improvements in metastasis-free survival. We used a discrete choice experiment (DCE) to examine how nmCRPC patients (pts) and caregivers perceive the benefits versus risks of SGARIs. Methods: nmCRPC pts and caregivers were invited to complete an online DCE survey of 14 treatment choice questions, each comparing 2 hypothetical medication profiles varying in terms of 5 safety attributes (frequency or severity of adverse events [AEs]: fatigue, skin rash, cognitive problems, serious falls, and serious fractures) and 2 efficacy attributes (duration of overall survival [OS] and time to pain progression). These attributes were selected based on in-depth qualitative interviews with pts, caregivers, and physicians. We used random parameters logit models to estimate preference weights and relative importance scores for each attribute. Results: 143 nmCRPC pts and 149 caregivers were included in the analysis. Both pts and caregivers viewed safety attributes in the following decreasing order of importance: fractures, falls, cognitive problems, fatigue, and rash. Compared to a reduction in rash severity from moderate to none, a similar reduction in cognitive problems severity was considered nearly as important by patients but twice as important by caregivers. On average, pts were willing to trade 5.8 and 4.0 months of OS to reduce the risks of serious fractures and falls, respectively, from 3% to 0%; the corresponding figures caregivers were willing to trade were 6.6 and 5.4 months of OS. Of note, 8.4% of pts and 14.8% of caregivers consistently chose the treatment profile with the lowest fall or fracture risk, regardless of the other attributes' values. Conclusions: nmCRPC pts and caregivers preferred treatments with lower AE burdens and were willing to trade substantial amounts of OS to avoid AEs. They viewed the reduction of fractures, falls, and cognitive problems as most important. In this relatively asymptomatic population, carefully balancing risks and benefits when selecting SGARI treatments is important to optimizing quality of survival.

e16556 Background: The castration-resistant nmPC treatment landscape has evolved following the recent approval of enzalutamide and abiraterone. Skin rash, fractures, and central nervous system (CNS) AEs have been reported among pts treated with these drugs as well as other antiandrogens (eg. bicalutamide). We assessed the rate and predictors of AEs among nmPC pts treated with abiraterone, enzalutamide, or bicalutamide (“study drugs”) in a real-world setting. Methods: nmPC pts initiating one of the study drugs ≥1 year after medical/surgical castration were identified in the MarketScan Commercial database (2012-17). We included pts who had all the following: a claim for a prostate-specific antigen test or an oncologist visit ≤6 months (mos) before study drug initiation (baseline period), no claim for hormonal therapies (except castration) nor metastasis before study drug, and ≥3-mos metastasis-free follow-up while on study drug. Kaplan Meier analyses were used to describe the rates and median time to onset for 18 CNS AEs (including, but not limited to, fatigue, cognitive impairment, or falls) or any AE (i.e., CNS AE, skin rash, or fracture). Baseline period AE predictors were identified using multivariate Cox-proportional hazards models. Results: 532 pts were included (bicalutamide: 89.7%, enzalutamide: 4.3%, abiraterone: 6.0%). The percentages of pts experiencing CNS AEs/any AE were 19%/22% at 3 mos, 28%/35% at 6 mos, and 43%/52% at 12 mos. Median time to AE onset since study drug initiation was 17.9 mos (CNS AE) and 11.0 mos (any AE) respectively. Significant predictors of having any AEs included baseline period AEs (hazard ratio [HR]: 3.07 [2.35-4.02]), Charlson comorbidity index (1 vs 0) (HR: 1.51 [1.04-1.19]), surgical castration (HR: 1.50 [1.07-2.08]), and older age (HR: 1.021 [1.002-1.040]). Similar predictors were found for CNS AE. Conclusions: nmPC pts treated with bicalutamide, enzalutamide or abiraterone experience high AE rates. Balancing the risks/benefits of treatment in this largely asymptomatic population is paramount to maintaining their quality of survival while optimizing survival outcomes.

e12562 Background: While no uniform standard of care exists for mTNBC, conventional chemotherapy remains the treatment mainstay. This retrospective analysis of U.S. commercial claims data was conducted to characterize real-world longitudinal chemotherapy treatment patterns and predictors of AEs in mTNBC. Methods: We assessed all pts with mTNBC aged 18-60 years starting first-line (1L) chemotherapy from 01/01/2011 to 12/31/2015 in the IMS LifeLink database, which does not report on investigational therapies. Longitudinal treatment patterns, treatment duration, and AEs were characterized by line-of-therapy (LOT). The primary and secondary endpoints were any AE and treatment duration. Multivariable logistic and Cox regression analyses were used to identify clinical risk factors for AEs and predictors of longer treatment duration, respectively. Results: 1,447 mTNBC pts receiving ≥1 LOT were identified (median [range] age, 51 [24-60] years), of which 54% received ≥2 and 8% ≥3 LOT. Combination therapy (combi-Tx) was used as 1L for 73%, second-line (2L) for 22%, and third-line (3L) for 32% of pts. The most common combi-Tx was cyclophosphamide/doxorubicin (1L: 40%; 2L: 5%), and carboplatin/gemcitabine in 3L (17%). The most common 1L and 2L monotherapies (mono-Tx) were taxanes (10% and 66%), and 3L capecitabine (13%). Median treatment duration for 1L to 3L was 56-58 days, and for combi- vs mono-Tx in 1L, 50 vs 71 days. The proportion of pts experiencing any AE was 34% during 1L, 38% during 2L, and 56% during 3L therapy. After adjusting for key confounders including Charlson comorbidity index, independent risk factors for AEs were later LOT, 3L vs 1L (OR = 3.20, 95%CI: 2.13-4.79), and younger age groups vs age 55-60 (OR = 1.94, 95%CI: 1.48-2.55). Additional analysis will assess independent predictors of treatment duration. Conclusions: This real-world study reveals considerable treatment heterogeneity and short treatment durations even with conventional combination chemotherapies. Among non-Medicare mTNBC pts, younger age is a risk factor for AEs possibly due to more aggressive therapies. More treatment options are needed for pts with mTNBC.

e16610 Background: Second-generation androgen receptor inhibitors (SGARIs) are now available for the management of nmCRPC based on improvements in metastasis-free survival. We used a discrete choice experiment (DCE) to explore how U.S. oncologists and urologists may balance different SGARIs’ risks (i.e., adverse events [AEs]) against survival, when treating an otherwise asymptomatic patient population. Methods: We invited oncologists and urologists treating nmCRPC patients via online panels to participate. The survey included 14 treatment choice questions, each comparing 2 hypothetical medication profiles, which varied in terms of 5 safety and 2 efficacy attributes. These attributes were selected via qualitative interviews and pre-testing with physicians, patients, and caregivers. We described safety attributes (fatigue, skin rash, cognitive problems, falls, and fractures) in terms of severity and frequency and efficacy attributes (overall survival [OS] and time to pain progression) in terms of duration of effect. We used a main-effects random parameters logit model to estimate preference weights and importance scores for each attribute. Results: 74 oncologists and 75 urologists completed the survey. Among safety attributes, physicians were most concerned with cognitive problems, fractures, and fatigue. Physicians placed 36% more importance on reducing cognitive problems from severe to none compared to improving OS by 12 months instead of 3 months. On average, physicians were willing to trade off 7.1 months of OS for a reduction in fatigue severity from severe to mild/moderate and 0.8 months of OS for a reduction in fatigue from mild/moderate to none. Physicians were willing to trade off approximately 4.2 and 5.0 months of OS for reduction in fracture risk from 8% to 5%, and 5% to 0%, respectively. Conclusions: As shown in this DCE, physicians making treatment decisions for largely asymptomatic nmCRPC patients, were willing to trade substantial amounts of survival to avoid AEs. These results emphasize the importance of carefully balancing the risk-benefit profiles of SGARI therapy when treating this patient population, to ultimately optimize the overall quality of the patients’ survival.