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Aim: Investigate oncologist and patient preferences for the first-line treatment of advanced urothelial carcinoma. Materials & methods: A discrete-choice experiment was used to elicit treatment attribute preferences, including patient treatment experience (number and duration of treatments and grade 3/4 treatment-related adverse events), overall survival and treatment administration frequency. Results: The study included 151 eligible medical oncologists and 150 patients with urothelial carcinoma. Both physicians and patients appeared to prefer treatment attributes related to overall survival, treatment-related adverse events and the number and duration of the medications in a regimen over frequency of administration. Overall survival had the most influence in driving oncologists' treatment preferences, followed by the patient’s treatment experience. Patients found the treatment experience the most important attribute when considering options, followed by overall survival. Conclusion: Patient preferences were based on treatment experience, while oncologists preferred treatments that prolong overall survival. These results help to direct clinical conversations, treatment recommendations and clinical guideline development.

BACKGROUND In 2022, it was estimated that more than 80,000 new cases of bladder cancer (BC) were diagnosed in the United States, 12% of which were locally advanced or metastatic BC (advanced BC). These forms of cancer are aggressive and have a poor prognosis, with a 5-year survival rate of 7.7% for metastatic BC. Despite recent therapeutic advances for advanced BC, little is known about patient and caregiver perceptions of different systemic treatments. To further explore this topic, social media can be used to collect the perceptions of patients and caregivers when they discuss their experiences on forums and online communities. OBJECTIVE The aim of this study was to assess patient and caregiver perceptions of chemotherapy and immunotherapy for treating advanced BC from social media–posted data. METHODS Public posts on social media in the United States between January 2015 and April 2021 from patients with advanced BC and their caregivers were collected. The posts included in this analysis were geolocalized to the United States; collected from publicly available domains and sites, including social media sites such as Twitter and forums such as patient association forums; and were written in English. Posts mentioning any line of chemotherapy or immunotherapy were qualitatively analyzed by two researchers to classify perceptions of treatments (positive, negative, mixed, or without perception). RESULTS A total of 80 posts by 69 patients and 142 posts by 127 caregivers mentioning chemotherapy, and 42 posts by 31 patients and 35 posts by 32 caregivers mentioning immunotherapy were included for analysis. These posts were retrieved from 39 public social media sites. Among patients with advanced BC and their caregivers, treatment perceptions of chemotherapy were more negative (36%) than positive (7%). Most of the patients’ posts (71%) mentioned chemotherapy factually without expressing a perception of the treatment. The caregivers’ perceptions of treatment were negative in 44%, mixed in 8%, and positive in 7% of posts. In combined patient and caregiver posts, immunotherapy was perceived positively in 47% of posts and negatively in 22% of posts. Caregivers also posted more negative perceptions (37%) of immunotherapy than patients (9%). Negative perceptions of both chemotherapy and immunotherapy were mainly due to side effects and perceived lack of effectiveness. CONCLUSIONS Despite chemotherapy being standard first-line therapy for advanced BC, negative perceptions were identified on social media, particularly among caregivers. Addressing these negative perceptions of treatment may improve treatment adoption. Strengthening support for patients receiving chemotherapy and their caregivers to help them manage side effects and understand the role of chemotherapy in the treatment of advanced BC would potentially enable a more positive experience.

Background\ud \ud Health state utility values (‘utilities’) are an integral part of health technology assessment. Though traditionally categorised by disease status in oncology (i.e. progression), several recent assessments have adopted values calculated according to the time that measures were recorded before death. We conducted a simulation study to understand the limitations of each approach, with a focus on mismatches between the way utilities are generated, and analysed.\ud \ud \ud \ud Methods\ud \ud Survival times were simulated based on published literature, with permutations of three utility generation mechanisms (UGMs) and utility analysis methods (UAMs): (1) progression based, (2) time-to-death based, and (3) a ‘combination approach’. For each analysis quality-adjusted life-years (QALYs) were estimated. Goodness of fit was assessed via percentage mean error (%ME) and mean absolute error (%MAE). Scenario analyses were performed varying individual parameters, with complex scenarios mimicking published studies. The statistical code is provided for transparency and to aid future work in the area.\ud \ud \ud \ud Results\ud \ud %ME and %MAE were lowest when the correct analysis form was specified (i.e. UGM and UAM aligned). Underestimates were produced when a time-to-death element was present in the UGM but not included in the UAM, while the ‘combined’ UAM produced overestimates irrespective of the UGM. Scenario analysis demonstrated the importance of the volume of available data beyond the initial time period, for example follow-up.\ud \ud \ud \ud Conclusions\ud \ud We show that the use of an incorrectly or over-specified UAM can result in substantial bias in the estimation of utilities. We present a flowchart to highlight the issues that may be faced.\ud \ud \ud \ud Key Points for Decision Makers\ud \ud A mismatch between the data structure and analysis method results in biased and inaccurate estimates of utility values.\ud \ud Unexpectedly, analysing utilities as a combination of progression- and TTD-based values performed poorly, even if utilities were generated within a corresponding framework. Over-specification of analyses should therefore be avoided.\ud \ud The volume of data available has a marked impact on the accuracy of estimates; this especially means the duration of follow-up and number of long-term survivors.

BACKGROUND Locally advanced or metastatic bladder cancer (aBC) has a very poor prognosis. However, few studies have assessed the unmet needs and burden of aBC from the patient and the caregiver perspective. OBJECTIVE To identify the main discussion themes and the unmet needs of patients with aBC and their caregivers through analysis of social media posts. METHODS Social media posts were collected between January 2015 and April 2021 from US geolocalized sites using specific keywords for aBC. The verbatim posts were analyzed to identify main discussion themes using biterm topic modeling. Difficulties or unmet needs were further explored using qualitative research methods by 2 independent annotators until saturation of concepts. RESULTS A total of 688 posts from 262 patients and 1214 posts from 679 caregivers discussing aBC were identified. Analysis of 340 randomly selected patient posts and 423 randomly selected caregiver posts uncovered 33 unique unmet need categories among patients and 36 among caregivers. The main unmet patient needs were related to challenges regarding adverse events (29.5%) and the psychological impact of aBC (21.1%). Other patient unmet needs identified were prognosis or diagnosis errors (9.5%) and the need for better management of aBC symptoms (9.5%). The main unmet caregiver needs were related to the psychological impacts of aBC (26%), the need for support groups and to share experiences between peers (15.8%), and the fear and management of patient adverse events (12.4%). CONCLUSIONS Social media posts from patients with aBC and their caregivers highlighted the emotional burden of cancer for both patients and caregivers. Additional studies on patients with aBC and their caregivers are required to quantitatively explore the impact of aBC on quality of life.

Gurjyot K Doshi,1 Abhijeet Bhanegaonkar,2 Mairead Kearney,3 Murtuza Bharmal,2 Paul Cislo,4 Ruth Kim,4 Marley Boyd,5 Kathleen M Aguilar,5 Hemant Phatak2 1Texas Oncology, Houston, TX, USA; 2EMD Serono Research & Development Institute, Inc., Rockland, MA, USA; an affiliate of Merck KGaA, Darmstadt, Germany; 3Merck KGaA, Darmstadt, Germany; 4Pfizer Inc., New York, NY, USA; 5Data, Evidence and Insights, McKesson Life Sciences, The US Oncology Network, The Woodlands, TX, USACorrespondence: Abhijeet BhanegaonkarDirector, US Health Economics and Outcomes Research – Oncology, North America Medical Affairs, EMD Serono, Inc., One Technology Place, Rockland, MA 02370, USATel +1 781-681-2483Email abhijeet.bhanegaonkar@emdserono.comPurpose: Clinical trial evidence has affirmed the role for immuno-oncology (IO) treatment for locally advanced or metastatic urothelial carcinoma (la/mUC). This Study informing treatment Pathway dEcision in bladder cAnceR (SPEAR-Bladder) aimed to provide insight into the optimal sequencing of IO treatments among la/mUC patients treated in the US Oncology Network.Patients and Methods: This was a retrospective analysis of adult patients with la/mUC who initiated first-line chemotherapy followed by either IO therapy (C-IO subgroup) or chemotherapy (C-C subgroup) between 01/01/2015 and 04/30/2017 and included a potential follow-up period through 06/30/2017. Data were sourced from iKnowMed electronic health records. Patient and treatment characteristics were assessed descriptively, with Kaplan–Meier methods used to evaluate time-to-event outcomes, including overall survival (OS).Results: A total of 117 patients were included in this analysis (median age 69 years, 74.4% male, 88.0% Caucasian): 79 and 38 patients were in the C-IO and C-C subgroups, respectively. The median OS was 19.2 months among patients who received the C-IO sequence and 11.9 months among those who received the C-C treatment sequence.Conclusion: These results suggest that patients who received the C-IO treatment sequence had notable improvement in OS compared with those who received the C-C sequence. In light of the rapidly evolving therapeutic landscape, further investigation will be required to determine how best to select the optimal therapeutic regimen and sequencing for patients with la/mUC.Keywords: urothelial carcinoma, SPEAR-Bladder, real-world clinical outcomes, treatment sequencing, retrospective, community oncology setting

Background and Objective Avelumab is approved for the treatment of metastatic Merkel cell carcinoma, a rare aggressive skin cancer with a poor prognosis. The aim of this qualitative study embedded in a clinical trial was to explore patient experiences while receiving avelumab. Methods All treatment-naïve patients with metastatic Merkel cell carcinoma entering part B of the phase II, open-label, international, JAVELIN Merkel 200 trial (NCT02155647) were invited to participate in optional semi-structured phone interviews before avelumab administration (baseline) and at weeks 13 and 25. Interviews were conducted by trained professionals, audio-recorded, transcribed and analysed. Key concepts identified at baseline were assessed during follow-up interviews. Results Twenty-nine patients completed the baseline interview; 19 had at least one follow-up interview. Baseline interviews described the patients’ challenging journeys before being correctly diagnosed with Merkel cell carcinoma, the negative psychological burden of living with a symptomless disease and the hope for avelumab to be a successful therapy. During the trial, most patients reported an increased or continued sense of hope and willingness to fight metastatic Merkel cell carcinoma. Patients who self-reported disease improvement (n = 12) also reported stability or improvement in physical well-being and ability to do daily activities, having more energy, worrying less and being optimistic. Six patients who reported their condition as stable (n = 4) or worsened (n = 3) reported a worsening of physical well-being. Nine patients reported fatigue/tiredness on the day of and after receiving avelumab. Baseline and longitudinal experiences were similar across countries. Conclusions This study suggests that patients experience perceptible benefits in physical and psychological well-being following treatment success with first-line avelumab in metastatic Merkel cell carcinoma.

BackgroundMerkel cell carcinoma (MCC) is a rare, aggressive cutaneous neuroendocrine neoplasm with annual incidence rates ranging from 0.13 to 1.6 cases per 100,000 per year.1 Chemotherapy for metastatic MCC (mMCC) has high objective response rates (ORRs), but responses are not durable and overall survival (OS) is poor. In March 2017, avelumab (anti–PD-L1) was approved for the treatment of mMCC and has demonstrated meaningful survival benefit and durable response.2 This study sought to investigate real-world clinical outcomes of avelumab-treated patients with advanced (stage IIIB/IV) MCC in academic medical centers in the United States (US).MethodsA retrospective chart review study of patients with advanced MCC who initiated avelumab between March 1, 2017, and July 31, 2019 was conducted at 6 US academic medical centers across the 4 US census regions. Eligible patients were followed through December 30, 2020. Descriptive analyses were conducted to assess demographics, clinical characteristics, and outcomes. Kaplan-Meier curves were constructed to illustrate real-world duration of response (rwDOR), real-world progression free survival (rwPFS), OS, and time-to-treatment discontinuation.ResultsNinety patients with advanced MCC were treated with avelumab, with a median follow-up of 15.0 months (95% CI, 13.1–17.8). Median age was 68 years; the majority were male (58%) and White (93%). During the time of avelumab initiation, 74 patients had stage IV MCC and 16 patients had stage IIIB MCC. Primary tumor was located most commonly on the lower limb (38%), with metastasis primarily to lymph nodes (67%) and lung (52%); 52% of patients had visceral metastases. Approximately 42% and 26% of patients had an Eastern Cooperative Oncology Group (ECOG) performance status of 2 and 3, respectively. Seventy-three patients (81%) received avelumab as first-line treatment of advanced MCC, whereas 17 (19%) received avelumab as second-line or later. Median duration of avelumab treatment was 13.5 months (95% CI, 6.4–30.6); 58% discontinued by the end of follow-up. Patients with avelumab treatment (n=90) had a rwORR of 73% (95% CI, 64–83), median rwPFS of 24.4 months (95% CI, 8.3-not reached [NR]), and median OS of 30.7 months (95% CI, 11.2-NR). Other clinical outcomes by line of avelumab treatment and stage at avelumab initiation are reported in table 1.ConclusionsThis real-world study of patients with advanced MCC treated with avelumab demonstrates high response rate with durable responses and prolonged survival. The study findings are consistent with the efficacy results demonstrated in pivotal clinical trials2 and other recent observational studies.3 4AcknowledgementsThe authors would like to acknowledge all physicians at the respective sites who participated in the data collection process for the study.ReferencesMüller-Richter UDA, Gesierich A, Kübler AC, Hartmann S, Brands RC. Merkel cell carcinoma of the head and neck: recommendations for diagnostics and treatment. Ann Surg Oncol 2017;24:3430–3437.D'Angelo SP, Bhatia S, Brohl AS, et al. Avelumab in patients with previously treated metastatic Merkel cell carcinoma: long-term data and biomarker analyses from the single-arm phase 2 JAVELIN Merkel 200 trial. J Immunother Cancer 2020;8:e000674.Cowey CL, Liu FX, Kim R, et al. Real-world clinical outcomes with first-line avelumab in locally advanced/metastatic Merkel cell carcinoma in the USA: SPEAR-Merkel. Future Oncol 2021;17:2339–2350.Levy S, Aarts MJB, Eskens FALM, et al. Avelumab for advanced Merkel cell carcinoma in the Netherlands: a real-world cohort. J Immunother Cancer 2020;8:e001076.Ethics ApprovalThe study was approved by New England Institutional Review Board.Abstract 628 Table 1Clinical outcomes among avelumab-treated patients with advanced MCC by line-of-treatment and stage at avelumab initiation

Aim: There is a need to evaluate current treatments for stages I–III of Merkel cell carcinoma (MCC). Materials & methods: A systematic literature review was conducted to understand how patients with stage I–III MCC are treated and assess efficacy, safety, health-related quality of life and economic impact of current therapies. Embase was searched using the following inclusion criteria: publications from 2014 to 2019, in English, with adult patients (≥18 years) with early-stage MCC (i.e., stages I–III) and any interventions/comparators. Publications were excluded if they included only patients with stage IV MCC, had no distinction between early and advanced or metastatic MCC or had no extractable data. Results: A total of 18 retrospective studies were included. Few studies had evidence that surgery plus adjuvant radiotherapy significantly increased survival versus surgery alone in early MCC. Limited safety data were reported in three studies. None of the studies reported data on health-related quality of life or economic impact of treatment in patients with early-stage MCC. Conclusion: Although surgery plus adjuvant radiotherapy was a common treatment, no clear standard of care exists for stages I–III MCC and treatment outcomes need to be improved. All studies were retrospective with a high variability in sample sizes; hence, findings should be interpreted with caution.

Introduction: The treatment landscape in locally advanced/unresectable or metastatic urothelial carcinoma (aUC) has evolved with the use of immune checkpoint inhibitors (ICIs) in the first line (1L) and platinum-refractory settings and with the recent approval of avelumab as 1L maintenance therapy for patients achieving disease control with platinum-containing regimens. Oncology provider perspectives and decision-making processes regarding aUC management, especially with the integration of recently approved strategies, such as maintenance therapy, have not been well-described. Patients and Methods: Qualitative interview study with US oncologists and oncology nurses in academic and community settings in August 2020. Interviews explored decision-making around aUC 1L treatment eligibility determinants and selection, programmed cell death 1 ligand 1 (PD-L1) testing practices, and use of maintenance therapy. Thematic analysis was used to identify drivers of 1L treatment decisions. Results: Eighteen oncologists (women, 11%; >15 years in practice, 55%; academic, 39%) and 18 oncology nurses (women, 94%; >15 years in practice, 34%; academic, 50%) participated. Providers preferred platinum-based regimens in 1L setting and reserved 1L ICI monotherapy for frail patients. Providers preferred chemotherapy followed by switch maintenance ICI, as opposed to concurrent combination chemotherapy and ICI, followed by ICI as continuation maintenance. Decision-making was driven by need to adhere to treatment decision-making guidelines, characteristics of the patient, treatment efficacy and patient preference. Conclusion: Providers adhered to guidelines and level I evidence in decision-making in the aUC 1L setting. Future studies should further evaluate barriers to the adoption of standard-of-care strategies and factors impacting decision-making in the real-world setting. Microabstract Treatment decision-making processes for advanced urothelial carcinoma (aUC) are not well defined; therefore, we conducted a qualitative interview study with US oncologists and oncology nurses. Providers preferred platinum-based first-line (1L) chemotherapy regimens followed by switch-maintenance immune checkpoint inhibitor (ICI) among those without disease progression (reserving 1L ICI monotherapy for frail patients). Overall, providers adhered to guidelines for decision-making in the 1L aUC setting.

Thitima Kongnakorn,1 Murtuza Bharmal,2 Mairead Kearney,3 Hemant Phatak,4 Agnes Benedict,5 Abhijeet Bhanegaonkar,4 Matthew Galsky6 1Evidence Synthesis, Modeling and Communication, Evidera, London, UK; 2Global Evidence and Value Development, EMD Serono, Inc. (A business of Merck KGaA, Darmstadt, Germany), Rockland, MA, USA; 3Global Evidence and Value Development, Merck KGaA, Darmstadt, Germany; 4US Health Economics and Outcomes Research, EMD Serono, Inc. (A business of Merck KGaA, Darmstadt, Germany), Rockland, MA, USA; 5Evidence Synthesis, Modeling and Communication, Evidera, Budapest, Hungary; 6Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USACorrespondence: Murtuza BharmalGlobal Evidence and Value Development, EMD Serono, Inc. (A business of Merck KGaA, Darmstadt, Germany), Rockland, MA, USAEmail murtuza.bharmal@emdserono.comObjective: To estimate the budget impact of introducing avelumab as a second-line (2L) treatment option for patients with locally advanced or metastatic urothelial cancer (mUC) from the perspective of a US third-party payer (commercial and Medicare).Methods: A budget impact model (BIM) with a three-year time horizon was developed for avelumab. Efficacy and safety data were sourced from published literature and US package inserts. The analysis was conducted in collaboration with a specialist oncologist who validated clinical assumptions. Costs were based on the number of eligible patients, time-to-treatment failure, overall survival, adverse events (AEs), and projected market shares of various treatments.Results: In a hypothetical commercial health plan of 30,000,000 members, 884 patients were estimated to be eligible for 2L treatment over a three-year time period. Without avelumab, the total cost for treating patients with mUC was estimated to be US$70,268,035. The introduction of avelumab increased total costs by $73,438 (0.10% increase). In a hypothetical Medicare health plan of 30,000,000 beneficiaries, a total of 4,705 patients were estimated to be eligible for 2L treatment. Without avelumab, the total cost for treating patients with mUC was estimated to be $292,923,098 from a Medicare perspective; however, with avelumab, there was an increase of $719,324 (0.25% increase) in total costs. Results of the sensitivity analyses demonstrated a cost-neutral impact across all tested scenarios from both perspectives.Conclusion: The BIM estimated that avelumab would have a cost-neutral impact within a US commercial and a Medicare health plan. Overall, avelumab can be an affordable and valuable treatment option for patients with locally advanced or mUC in the 2L setting. These findings demonstrate a consistently favorable budget impact in both populations. Further studies should be conducted to more comprehensively assess the clinical and economic implications of adding avelumab to the treatment armamentarium of 2L mUC.Keywords: urothelial carcinoma, budget impact model, cost analysis, economic analysis, immuno-oncology, chemotherapy

Background Response rates are primary endpoints in many oncology trials; however, correlation with overall survival (OS) is not uniform across cancer types, treatments, or lines of therapy. This study explored the association between objective response (OR) and OS in patients with chemotherapy-refractory metastatic Merkel cell carcinoma who received avelumab (anti-PD-L1). Methods Eighty-eight patients enrolled in JAVELIN Merkel 200 (part A; NCT02155647) received i.v. avelumab 10 mg/kg every 2 weeks until confirmed progression, unacceptable toxicity, or withdrawal. Using conditional landmark analyses, we compared OS in patients with and without confirmed OR (RECIST v1.1). We applied a Cox model that included OR as a time-varying covariate and adjusted for age, visceral disease, and number of previous therapies. Results Twenty-nine patients had confirmed OR; 20 by study week 7 and 7 more between study weeks 7 and 13. Survival probabilities 18 months after treatment initiation were 90% [95% confidence interval (CI) 65.6–97.4] in patients with OR at week 7 and 26.2% (95% CI 15.7–37.8) in patients without OR but who were alive at week 7. Median OS was not reached in patients with OR and was 8.8 months (95% CI 6.4–12.9) in patients without. Similar results were observed for the week 13 landmark. The adjusted Cox model showed OR was associated with a 95% risk reduction of death [hazard ratio 0.052 (95% CI 0.018–0.152)] compared with a nonresponse. Conclusions Patients with OR by 7 or 13 weeks had significantly longer OS than patients without, confirming that early OR is an endpoint of major importance.

Background\ud \ud Metastatic Merkel cell carcinoma (mMCC) is a rare and aggressive skin cancer. Until recently, there were no licensed treatment options for patients with mMCC, and prognosis was poor. A cost-effectiveness analysis was conducted for avelumab, a newly available treatment option for mMCC, versus standard care (SC), from a UK National Health Service perspective.\ud \ud \ud Methods\ud \ud A partitioned survival model was developed to assess the lifetime costs and effects of avelumab versus SC. Data from the JAVELIN Merkel 200 trial (NCT02155647) were used to inform estimates of quality-adjusted life-years (QALYs). Unit costs and associated frequencies of use were informed by published literature and clinical expert opinion. Results were presented as incremental cost-effectiveness ratios (ICERs, i.e. the cost per QALY gained) for treatment-experienced (TE) and treatment-naïve (TN) patients. Uncertainty was explored through a range of sensitivity analyses.\ud \ud \ud Results\ud \ud Discounting costs and QALYs at 3.5% per annum, avelumab was associated with ICERs of £35,274 (TE)/£39,178 (TN) per QALY gained. Probabilistic sensitivity analysis results demonstrated that avelumab was associated with an 88.3% (TE)/69.3% (TN) probability of being cost effective at a willingness-to-pay threshold for end-of-life treatments of £50,000 per QALY gained. Results were most sensitive to alternative survival extrapolations and dosing assumptions.\ud \ud \ud Conclusions\ud \ud The analysis results suggest that avelumab is likely to be a cost-effective treatment option for UK mMCC patients. The results for TN patients are subject to some uncertainty, and a confirmatory analysis will be conducted with more mature data.

Aim: To evaluate changes in health-related quality of life (HRQoL) in a Phase II trial (NCT02155647) of treatment-naive patients with metastatic Merkel cell carcinoma treated with avelumab (15-month follow-up). Materials & methods: Mixed-effect Models for Repeated Measures were applied to HRQoL data (FACT-M; EQ-5D-5L) to assess changes over time. Clinically derived progression-free survival was compared with HRQoL deterioration-free survival. Results: Overall, we saw relative stability in HRQoL among 116 included patients, with nonprogression associated with statistically and clinically meaningful better HRQoL compared with progressive disease. Deterioration-free survival rates (49–72% at 6 months, 40–58% at 12 months) were consistently higher/better compared with progression-free survival rates (41/31% at 6/12 months). Conclusion: These findings show unique longitudinal HRQoL data for treatment-naive metastatic Merkel cell carcinoma patients treated with avelumab. Clinical trial registration: NCT02155647 ( ClinicalTrials.gov ).

Objectives For valid and reliable assessment of patients’ Health-Related Quality of Life (HRQoL), it is crucial to use psychometrically robust instruments. In the context of rare diseases such as Merkel cell carcinoma (MCC), validated disease-specific instruments are often not available. The Functional Assessment of Cancer Therapy – Melanoma (FACT-M) was originally developed for use in melanoma. Its psychometric performance for use in MCC and minimal important difference (MID) thresholds have been previously reported based on a cohort of metastatic MCC patients who had disease progression following one or more prior line of chemotherapy (NCT02155647 Part A; n = 70). Since then, new data from the phase II JAVELIN Merkel 200 trial among treatment-naïve patients are available (NCT02155647 Part B; n = 102). This study aims to increase accuracy and precision of previously established psychometric properties and MID thresholds of FACT-M in metastatic MCC patients. Methods Published qualitative research suggests that patients with metastatic MCC had similar experiences and described similar concepts associated with their disease independent of whether they were treatment naïve or had prior treatment. Therefore, it was deemed appropriate to pool FACT-M data from Part A (previously treated) and Part B (treatment-naïve) cohorts for this study. Construct validity was assessed by evaluating item-factor correlations (convergent validity) and known-groups validity using ECOG performance status 0 versus 1. Concurrent validity was assessed using EQ-5D items. Internal consistency reliability was assessed using Cronbach’s α. Anchor- and distribution-based approaches were used to derive MID thresholds. Results Overall, psychometric tests based on various validity (convergent, known-groups, concurrent) and reliability (Cronbach α) analyses confirmed previous findings in that FACT-M performs well in MCC patients. MID thresholds derived from this study are largely in line with previously established thresholds with some minor adjustments. Conclusions In the context of rare diseases, which often have limited data available for psychometric testing, a reasonably large MCC patient sample was available for this study, enhancing accuracy and precision of previously established FACT-M psychometric properties and MID thresholds with only small deviations for use in metastatic MCC patients. Results suggest that the FACT-M is suitable for Merkel cell carcinoma regardless of patients’ treatment status. Trial registration This study is a pre-planned post-hoc analysis conducted on data collected in Part A and Part B of the JAVELIN Merkel 200 trial. This trial was registered on 2 June 2014 with ClinicalTrials.gov as NCT02155647.

In this Publication Perspective, authors Murtuza Bharmaland and Venediktos Kapetanakis discuss their paper "Assessment-schedule matching in unanchored indirect treatment comparisons of progression-free survival in cancer studies" published in PharmacoEconomics.

Background\ud The timing of efficacy-related clinical events recorded at scheduled study visits in clinical trials are interval censored, with the interval duration pre-determined by the study protocol. Events may happen any time during that interval but can only be detected during a planned or unplanned visit. Disease progression in oncology is a notable example where the time to an event is affected by the schedule of visits within a study. This can become a source of bias when studies with varying assessment schedules are used in unanchored comparisons using methods such as matching-adjusted indirect comparisons.\ud \ud Objective\ud We illustrate assessment-time bias (ATB) in a simulation study based on data from a recent study in second-line treatment for locally advanced or metastatic urothelial carcinoma, and present a method to adjust for differences in assessment schedule when comparing progression-free survival (PFS) against a competing treatment.\ud \ud Methods\ud A multi-state model for death and progression was used to generate simulated death and progression times, from which PFS times were derived. PFS data were also generated for a hypothetical comparator treatment by applying a constant hazard ratio (HR) to the baseline treatment. Simulated PFS times for the two treatments were then aligned to different assessment schedules so that progression events were only observed at set visit times, and the data were analysed to assess the bias and standard error of estimates of HRs between two treatments with and without assessment-schedule matching (ASM).\ud \ud Results\ud ATB is highly affected by the rate of the event at the first assessment time; in our examples, the bias ranged from 3 to 11% as the event rate increased. The proposed method relies on individual-level data from a study and attempts to adjust the timing of progression events to the comparator’s schedule by shifting them forward or backward without altering the patients’ actual follow-up time. The method removed the bias almost completely in all scenarios without affecting the precision of estimates of comparative effectiveness.\ud \ud Conclusions\ud Considering the increasing use of unanchored comparative analyses for novel cancer treatments based on single-arm studies, the proposed method offers a relatively simple means of improving the accuracy of relative benefits of treatments on progression times.

Background Merkel cell carcinoma (MCC) is a rare and aggressive skin cancer with limited treatment options at advanced stages. There is a paucity of data available regarding the impact of MCC and its management on patients’ lives. This study aimed to address this gap by interviewing patients with metastatic MCC entering a trial of an immunotherapy (avelumab). Methods In a single-arm, open-label, international, phase 2 trial in patients with stage IV, chemotherapy-refractory, histologically confirmed MCC, patients were invited to participate in semi-structured phone interviews. These were conducted before avelumab administration. Interview transcripts were analysed qualitatively to identify concepts important to patients relating to their experience of metastatic MCC and its management. Results Nineteen patients were interviewed. Most reported MCC to be painless and asymptomatic. They reported being often misdiagnosed and described a long process before receiving the correct diagnosis. They also reported a feeling of “shock” after being informed of the severity and seriousness of their cancer. Overall, patients did not report impaired physical and cognitive capacities or impact on daily lives, either before or after diagnosis. However, patients and their relatives reported feelings of “worry” and “fear” about the unknown outcome of the disease. Chemotherapy and radiotherapy negatively affected patients physically and psychologically in their everyday lives. Conclusions MCC disease was not perceived by the interviewed patients to result in severe functional limitations or to severely impact everyday activities, but was associated with substantial negative psychological impact. In contrast, chemotherapy and radiotherapy for MCC are highly debilitating and disrupt patients’ lives. ClinicalTrials.gov identifier NCT02155647.

// Jurgen C. Becker 1, 2, 15 , Eva Lorenz 3, 14 , Selma Ugurel 2 , Thomas K. Eigentler 4 , Felix Kiecker 5 , Claudia Pfohler 6 , Ivonne Kellner 7 , Friedegund Meier 8, 16 , Katharina Kahler 9 , Peter Mohr 10 , Carola Berking 11 , Gabriele Haas 2 , Christoph Helwig 12 , Dina Oksen 12 , Dirk Schadendorf 2 , Lisa Mahnke 13 and Murtuza Bharmal 12 1 Translational Skin Cancer Research (TSCR), German Cancer Research Center (DFKZ) Partner Site Essen/Dusseldorf, Essen University Hospital, 45147, Essen, Germany 2 Department of Dermatology, University Hospital of Essen, 45122 Essen, Germany 3 IMS HEALTH GmbH and Co OHG, 60598, Frankfurt am Main, Germany 4 Department of Dermatology, University Hospital of Tubingen, 72076 Tubingen, Germany 5 Charite Universitatsmedizin Berlin, Department of Dermatology, 10117 Berlin, Germany 6 Saarland University Medical School, Department of Dermatology, 66421 Homburg/Saar, Germany 7 Helios-Klinik, Department of Dermatology, 99089 Erfurt, Germany 8 Skin Cancer Center, University Cancer Centre, and National Center for Tumor Diseases Dresden, 01307 Dresden, Germany 9 Universitatsklinikum, Department of Dermatology, 24105 Kiel, Germany 10 Elbe-Kliniken, Skin Cancer Center, 21614 Buxtehude, Germany 11 University Hospital Munich (LMU), Department of Dermatology and Allergy, 80337 Munich, Germany 12 Merck KGaA, 64293 Darmstadt, Germany 13 EMD Serono, Inc., Billerica, MA, 01821, USA 14 Present address: Institute for Medical Statistics, Epidemiology and Informatics, University Medical Center Mainz, 55131 Mainz, Germany 15 Department of Dermatology, University Hospital of Wurzburg, 97080, Wurzburg, Germany 16 Department of Dermatology, University Hospital Carl Gustav Carus at the TU Dresden, 01307 Dresden, Germany Correspondence to: Jurgen C. Becker, email: j.becker@dkfz.de Keywords: Merkel cell carcinoma, skin cancer, retrospective study, chemotherapy, observational study Received: April 25, 2017 Accepted: June 27, 2017 Published: July 13, 2017 ABSTRACT Background and aims: Merkel cell carcinoma (MCC) is a rare, aggressive skin cancer; few treatments exist for patients with advanced disease. Once tumors metastasize to distant sites, patients generally receive chemotherapy, but response duration and progression-free survival (PFS) are typically short. Few studies have assessed the efficacy of second-line chemotherapy for metastatic MCC. Here, we studied outcomes in patients who received ≥ 2 lines of chemotherapy for metastatic MCC. Materials and Methods: Patients in an MCC-specific registry diagnosed with stage IV MCC between November 1, 2004, and September 15, 2015, and treated with second-line or later chemotherapy were analyzed retrospectively. Patient records, including baseline characteristics, immunocompetent status, and responses to prior chemotherapy, were evaluated. Patients meeting eligibility criteria were followed through December 31, 2015. Results: Of 29 patients with metastatic MCC and immunocompetent status who had received ≥ 2 lines of chemotherapy, 3 achieved a partial response, for an objective response rate (ORR) of 10.3% (95% CI, 2.2–27.4). In the overall population including patients with immunocompetent and immunocompromised status ( n = 34), the ORR was 8.8% (95% CI, 1.9–23.7). The median duration of response was 1.9 months (range, 1.3–2.1 months; 95% CI, 1.3–2.1). In the immunocompetent population, median PFS and overall survival were 3.0 months (95% CI, 2.5–6.0) and 5.3 months (95% CI, 4.3–6.0), respectively. Conclusions: The low response rates and limited durability confirm previous reports of the ineffectiveness of second-line or later chemotherapy in patients with metastatic MCC and provide a benchmark for assessing clinical benefit of new treatments.

407 Background: Avelumab first-line (1L) maintenance therapy for patients (pts) with advanced/mUC that has not progressed with platinum-containing chemotherapy was recently approved in the US based on improved overall survival seen in the JAVELIN Bladder 100 trial. However, provider perspectives regarding 1L maintenance therapy in mUC have not been reported. Methods: We performed a qualitative interview study with US oncologists and oncology nurses treating pts with mUC in academic and community practices. Telephone interviews were conducted in August 2020 using a semi-structured discussion guide to explore decision-making processes about treatment for pts with mUC and perspectives about ICI maintenance therapy in the 1L setting. The latter was defined as either 1) ICI for pts who achieve disease control with platinum-containing chemotherapy (Regimen A) or 2) ICI + chemotherapy followed by ICI (Regimen B). Thematic analysis identified key determinants and clinical considerations associated with ICI maintenance therapy in mUC. Results: Results for 18 oncologists (mean age 51.3 yrs [SD 9]; 11% female; 55% with >15 yrs in practice; 39% academic) and 18 oncology nurses (mean age 43.8 yrs [SD 11.1]; 94% female; 34% with >15 yrs in practice; 50% academic) are reported. Cisplatin- and carboplatin-based chemotherapy regimens were the most commonly administered 1L treatments, with ICI monotherapy reserved only for frail (i.e., comorbid and/or elderly) pts. All oncologists recommended 4-6 cycles of 1L chemotherapy. Providers reported different perspectives about the maintenance approaches. Those who expressed a preference for Regimen A (oncologists, 66.6%; nurses, 71.4%) cited potentially less toxicity as a key factor driving their choice. Providers who preferred Regimen B cited the perceived potential for deeper and more durable responses based on previous experience with this maintenance approach in other tumors as a driver of their choice. For Regimen A, providers universally did not recommend a treatment break between chemotherapy and ICI maintenance because of concerns about progression. Frequency of administration was not cited as a driver of treatment decisions for either maintenance approach; instead, providers prioritized survival and tolerability. Responses were generally consistent between oncologists and nurses. Conclusions: Overall, providers adhered to new guidelines for 1L treatment of mUC (NCCN and ESMO) and expressed receptivity toward Regimen A. Although few providers had experience with this new regimen, most preferred it vs ICI + chemotherapy followed by ICI in 1L mUC. Our findings highlight the need to increase provider awareness of Regimen A, i.e., avelumab maintenance in pts with response or stable disease with 1L chemotherapy as a standard of care in advanced/mUC, which has Level I evidence.

573 Background: Population-adjusted comparisons of PFS from single-arm trials of cancer treatments can be derived using matching-adjusted indirect comparison (MAIC); however, results are still susceptible to bias, particularly if the trials had different tumor assessment schedules (favoring longer intervals). This is shown with an MAIC of avelumab vs atezolizumab, nivolumab, durvalumab, pembrolizumab or chemotherapy in 2L UC. Methods: The MAIC used patient-level data for avelumab from the JAVELIN Solid Tumor trial (NCT01772004) and compared PFS with published curves for other treatments to obtain population-adjusted hazard ratios (HRs). The first assessment was scheduled at 6 weeks for avelumab and durvalumab and at 8 or 9 weeks for the others. The MAIC was repeated after aligning the first assessment time for avelumab to each comparator’s schedule with the Assessment Schedule Matching (ASM) method. Results: Naïve analyses (Table) suggest similar PFS for avelumab vs comparators. MAIC based on population adjustment (PA) altered the HR of avelumab vs atezolizumab and nivolumab (23.0% and 9.2% reductions in HR, respectively) but had little effect in other comparisons. ASM adjustment led to further changes in HR (13.2-32.7% reductions from naïve) favoring avelumab in MAICs where schedules differed. Of note, assessment schedule differences fully accounted for differences in PFS between avelumab and pembrolizumab. Conclusions: Indirect comparisons of PFS from single-arm trials must include adjustment for differences in both population characteristics and tumor assessment schedules. In this 2L UC MAIC, adjustment reversed some naïve comparisons, revealing more favorable PFS with avelumab up to 30%. Clinical trial information: NCT01772004. [Table: see text]

Currently, there are 4 EQ-5D-5L scoring algorithms available for the United Kingdom that can be used to derive a utility score.To perform a psychometric validation of the EQ-5D utility score in patients with metastatic Merkel cell carcinoma (mMCC) and to compare 4 EQ-5D-5L value sets currently available for the United Kingdom.Data collected in the phase 2 trial JAVELIN Merkel 200 were analyzed, in which 88 patients with mMCC were treated with avelumab. Utility scores were calculated using the EQ-5D-5L valuation set by Devlin et al and 3 further algorithms that are based on EQ-5D-3L valuations. Criterion validity was assessed by Pearson correlations between utility and other HRQoL scales. Responsiveness was assessed by correlating change in utility scores with change in HRQoL scales and percentage change in tumor size. Effect sizes for change from baseline in utility were calculated in subgroups of patients with improving and deteriorating health based on clinically relevant changes in various external anchors.Devlin utilities were up to 0.10 points higher than utilities calculated from EQ-5D-3L valuations. Large correlations (0.45-0.72; P.01) between utility and the EuroQol Visual Analogue Scale and FACT-G total, physical, and functional scores were found for all 4 algorithms. Large correlations between these measures were also found for change from baseline scores. In patients with health improvements, effect sizes were larger for the 3 EQ-5D-3L-based algorithms, whereas the Devlin utilities had larger effect sizes for health deteriorations, probably because of different levels of baseline utility.The English National Institute for Health and Care Excellence currently recommends use of the 3L valuation sets. Our analyses show that all 4 scoring algorithms have good and similar psychometric properties in patients with mMCC.

To examine the characteristics of patients with newly-diagnosed Merkel cell carcinoma (MCC), analyze their treatment patterns and comorbidities after diagnosis, and evaluate the economic burden on the MCC patient population in the US.This observational, non-interventional cohort study identified patients with MCC that were newly-diagnosed between January 1, 2010 through December 31, 2014, and whose data were either in the MarketScan Commercial Claims and Encounters (CCAE) or Medicare Supplemental and Coordination of Benefits databases. Standard descriptive statistics were used to describe patient demographics, clinical characteristics, treatment regimens, and healthcare resource use (HRU) and cost.Following MCC diagnosis, most patients in the study population (n = 2,177) received only surgery (34.5%) or surgery and radiotherapy without chemotherapy (22.0%), while 14.5% of patients received none of these treatments; 27.5% of patients received at least one line of chemotherapy as part of their treatment. Mean total healthcare costs per patient per year (PPPY), as well as mean inpatient, outpatient, and pharmacy costs, were significantly greater for patients who received chemotherapy compared with those who received other or no treatments. Higher HRU and mean costs were associated with increasing patient comorbidity burden, ranging from $62,401 PPPY in Deyo Charlson Comorbidity Index level 1 to $109,690 in level ≥3.The study used claims databases that were limited to patients who are covered by large employer-sponsored insurance and/or Medicare and did not provide information regarding the rationale for treatment choice or resource use.The choice of treatment is a major factor in determining healthcare costs associated with MCC, with the highest costs in patients receiving chemotherapy. Patients with MCC often exhibit comorbidities, and both HRU and healthcare costs increase significantly with each comorbidity level.

Aim: To assess patient experience with chemotherapy and avelumab in metastatic Merkel cell carcinoma (mMCC). Methods: In the JAVELIN Merkel 200 trial, chemotherapy-refractory mMCC patients could participate in optional qualitative interviews at baseline documenting recollection of previous chemotherapy experience, and at weeks 13/25 documenting current experience with avelumab. Functional Assessment of Cancer Therapy subscale for melanoma questionnaire (FACT-M) was administered in parallel. Results: In our sample, chemotherapy was associated with an unpleasant experience. On selected FACT-M items addressing chemotherapy-impacted concepts, most patients receiving avelumab were improved or stable; few worsened. In addition, a few patients spontaneously reported experiencing less toxicity with avelumab than experienced during previous chemotherapy. Conclusion: This approach merging qualitative and quantitative data suggests that mMCC patients report a better experience with avelumab than with chemotherapy.

Aim: Real-world evidence of charted treatment responses to cancer drug therapy was compared with medical record derived radiographic measurements of target lesions per Response Evaluation Criteria in Solid Tumors (RECIST). Materials & methods: 15 physicians treating 59 metastatic Merkel cell cancer (mMCC) patients contributed patient-level data. A comparison of medical record reported best response with radiographic measurements per RECIST of pre- and post-treatment target lesions. Results: RECIST response rates were significantly lower compared with medical record reported with a concordance of 43.2% (95% CI: 28.0–58.4%). Conclusion: Subjective assessment of tumor response collected via traditional chart abstraction may overestimate benefit and limit the potential role of real-world evidence in value-based care research. The use of target lesion measurements presents an attractive alternative that better aligns with trial results.

Background Demonstrating treatment benefits within clinical trials in the context of rare diseases is often methodologically and practically challenging. Mixed methods research offers an approach to overcome these challenges by combining quantitative and qualitative data, thus providing a better understanding of the research question. A convergent mixed methods design in the context of Merkel cell carcinoma, a rare skin cancer, was used during the JAVELIN Merkel 200 trial (NCT02155647). Methods Nine patients receiving avelumab in the JAVELIN Merkel 200 trial were interviewed at baseline prior to receiving study treatment, and at 13 weeks and 25 weeks after first avelumab administration. Key concepts of interest identified from the baseline interviews were physical functioning, fatigue/energy, and pain. Patient perceptions of the overall change in their cancer-related health status since starting study treatment were also recorded. During qualitative analysis, at each time-point, each concept of interest was assigned a category describing the trend in change (e.g. newly emerged, no change/stable, improved, worsened, ceased/disappeared). In parallel, patients’ tumour status was determined by the clinical overall response status as per the clinical trial protocol. Results A high concordance between patient-reported qualitative data and assessed tumour response was observed. All eight patients who clinically improved had perceived a subjective improvement in their disease since the beginning of the study; the single patient whose disease worsened had a perceived deterioration. Patient perceived benefit in physical functioning, fatigue/energy and pain was subsequent to the measured change in clinical status as assessed by tumour response. This suggests that patient-reported assessment should be examined over the long term in order to optimally capture meaningful treatment effect. Conclusion Embedding qualitative research in clinical trials to complement the quantitative data is an innovative approach to characterise meaningful treatment effect. This application of mixed methods research has the potential to overcome the hurdles associated with clinical outcomes assessment in rare diseases.

Aim: To assess the association between tumor response and health-related quality of life (HRQoL) in patients with metastatic Merkel cell carcinoma treated with the anti-PD-L1 avelumab. Materials & methods: Phase II single-arm trial (NCT02155647) data of 88 patients were analyzed. Correlations between percentage reduction in tumor size and change from baseline in Functional Assessment of Cancer Therapy – General (FACT-G), FACT – Melanoma (FACT-M) and EuroQol-5 Dimension scores were calculated. HRQoL and utility by tumor response (per the Response Evaluation Criteria In Solid Tumors version 1.1) was estimated. Results: Tumor shrinkage correlated positively with patients’ change from baseline in the FACT-M total (0.364 [95% CI: 0.050–0.607]) and subscale scores. Differences in HRQoL and utility between nonprogressive disease and progressive disease were clinically relevant. Conclusion: In patients with metastatic Merkel cell carcinoma, nonprogression during treatment with avelumab correlated with gains in HRQoL.

Background No validated disease-specific questionnaires exist to capture health-related quality of life (HRQoL) in patients with Merkel cell carcinoma (MCC). The Functional Assessment of Cancer Therapy – Melanoma (FACT-M) is validated in patients with melanoma, which shares many similarities with MCC. This paper reports the psychometric properties of the FACT-M in the metastatic MCC population. Methods Data were collected as part of a single-arm, open-label, multicenter trial involving patients with metastatic MCC who had failed at least one previous line of chemotherapy. FACT-M and EQ-5D were administered at baseline, Week 7, Week 13, and Week 25. An optional interview was administered at the same time points. MCC-specific FACT-M scores were derived following a combined quantitative and qualitative approach. Reliability and construct validity of original and additional MCC-specific FACT-M scores were assessed at baseline. Capacity to detect change in tumor size was assessed from baseline to Week 7. Minimally important differences (MIDs) were computed using distribution and anchor-based methods. Results Baseline assessments were available in 70 patients (mean age: 70 years; 74.3% male); 19 patients were interviewed at baseline. Additional MCC-specific scores were as follows: Physical Function score (six items), Psychological Impact score (six items), and MCC summary score (12 items). FACT-M original and additional MCC-specific scores both demonstrated acceptable psychometric properties: high reliability (Cronbach’s alpha: 0.81–0.96), good convergent validity (correlations above 0.4 observed for 88% of items of the Melanoma surgery scale, 75% of items of the Melanoma scale, and 100% of items of the other FACT-M domains). Some evidence of floor/ceiling effects and poor discriminant ability was found. Higher scores (better HRQoL) on all FACT-M domains were observed in patients with better functioning (assessed by ECOG performance score), supporting clinical validity. Despite the small sample for responsiveness analysis (n = 37), the majority of FACT-M scores showed sensitivity to changes in tumor size at Week 7 with small to moderate effect sizes. MIDs were consistent with previously reported values in the literature for FACT-M domains. Conclusions FACT-M is suitable to capture HRQoL in patients with metastatic MCC, thus making it a potential candidate for assessing HRQoL in MCC trials. Trial registration This study is a post-hoc analysis conducted on data collected in Part A of the JAVELIN Merkel 200 trial. This trial was registered on 2 June 2014 with ClinicalTrials.gov as NCT02155647.

Aim: Merkel cell carcinoma (MCC) is a rare neuroendocrine, cutaneous malignancy with poor prognosis once metastasized. The aim of this study was to conduct a systematic literature review to assess clinical outcomes associated with chemotherapy regimens in metastatic MCC. Materials & methods: Embase®, MEDLINE®, MEDLINE®-In-Process and CENTRAL were searched for studies published in January 2016. Results & conclusion: Overall, the literature on chemotherapy in patients with metastatic MCC is sparse, with most studies being case series/reports. Across all studies, response rates ranged from 20 to 61%, with higher response rates in first-line setting (53–61%) versus second-line setting (23–45%). Among responders, duration of response was short (≤8 months) in both first- and second-line settings. There is a need for novel agents that can induce durable responses in metastatic MCC.

Merkel cell carcinoma (MCC) is a rare skin cancer that is associated with Merkel cell polyomavirus infection in most cases. Incidence rates of MCC have increased in past decades. Risk factors for MCC include ultraviolet light exposure, immunosuppression and advanced age. MCC is an aggressive malignancy with frequent recurrences and a high mortality rate, although patient outcomes are generally more favourable if the patient is referred for treatment at an early stage. Although advances have been made recently in the MCC field, large gaps remain with regard to definitive biomarkers and prognostic indicators. Although MCC is chemosensitive, responses in advanced stages are mostly of short duration, and the associated clinical benefit on overall survival is unclear. Recent nonrandomised phase 2 clinical trials with antiePD-L1/PD-1 antibodies have demonstrated safety and efficacy; however, there are still no approved treatments for patients with metastatic MCC. Patients with advanced disease are encouraged to participate in clinical trials for treatment, indicating the largely unmet need for durable, safe treatment within this population. (C) 2016 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

90 Background: MCC is a rare, aggressive skin cancer with a poor prognosis. Avelumab is the only anti–PD-L1 monoclonal antibody approved for treatment of mMCC. This qualitative research embedded in a clinical trial aimed to explore pt experiences on treatment with avelumab. Methods: All treatment-naive pts with mMCC entering the registrational, open-label, multicenter trial to investigate the clinical activity and safety of avelumab were invited to participate in optional, semistructured, 30-min phone interviews at baseline (prior to study drug administration) and at weeks 13 and 25. Interviews were conducted by trained professionals, audio-recorded, transcribed, and analyzed using a qualitative software package, ATLAS.ti V7. Key concepts identified from the baseline interview for each pt were assessed during follow-up interviews. Results: A total of 29 pts (mean age, 71 y; 76% male) completed the baseline interview; 19 pts (6 in USA, 4 in France, 5 in Italy, 3 in Germany, 1 in Australia) had ≥1 follow-up interview. The baseline interviews revealed the negative psychological burden on pts living with a symptomless disease and the hope for avelumab to be a successful therapy. Over the course of the trial, most pts reported an increased or continued sense of hope and willingness to fight MCC. Pts who self-reported their disease to be improved (n=12) also reported being stable or experiencing improvements in their ability to do their daily activities and in their physical well-being and having more energy than before starting avelumab. They also reported worrying less and being optimistic. Six pts among the 7 who reported their condition as stable (n=4) or worsened (n=3) reported a worsening of their physical well-being. Nine pts reported fatigue/tiredness on the day of and the day after receiving the avelumab infusion. The reported baseline and longitudinal experiences were similar across pts from all countries. Conclusions: This qualitative study alongside a registrational trial showed that pts experienced perceptible benefits in their physical and psychological well-being following treatment success with avelumab in mMCC. Clinical trial information: NCT02155647 part B.

453 Background: With the introduction of immunotherapy (IO) for locally advanced or metastatic urothelial carcinoma (mUC), optimal treatment sequence should be considered. This study aimed to compare time to treatment failure (TTF) and overall survival (OS) among these patients (pts) treated with first-line (1L) systemic chemotherapy followed by second-line (2L) IO ( C-IO) vs 1L and 2L chemotherapy ( C-C) sequence within the US community oncology Network (USON). Methods: This was a retrospective study of adult locally advanced or mUC pts who initiated systemic therapy between 1/1/15 – 4/30/17 within USON and had a minimum of two-month follow-up. Descriptive analyses were performed, with Kaplan-Meier used for comparisons between pts who received C-IO vs C-C sequence. Pts considered for this analysis did not receive a third-line treatment. Regression analyses were performed to assess variables associated with TTF and OS. Results: 117 pts were included in the analysis ( C-IO n = 79, C-C n = 38). Median age (range) was 69 years (38, 90+), with 74.4% male. Baseline demographic and clinical characteristics were similar between the groups. The median (range) duration between start of 1L and start of 2L therapy was significantly longer among C-IO vs C-C pts (29.0 [4.1, 102.1] vs 20.0 [0.1, 63.1] weeks; P = 0.0047). Median TTF and OS were longer among C-IO vs C-C pts but the trends were not significant (Table). The duration between initial diagnosis and advanced disease status was associated with TTF (P = 0.0124) in univariate analysis. Conclusions: These results suggest that patients receiving C-IO demonstrated greater (>30 weeks) but statistically non-significant improvement in OS versus those receiving C-C. Considering these OS trends, future research should explore prognostic characteristics of IL chemotherapy treated pts who may benefit from an earlier switch to IO therapy. [Table: see text]

To assess prevalence, disease burden, and costs of primary Restless Legs Syndrome (RLS) in the US. In 2007, 61,792 (20%) of 313,000 subjects from a representative US panel completed an online "global opinions" survey identifying respondents reporting all four diagnostic features of RLS. 4,484 met all criteria. 1,400 were randomly selected to complete a questionnaire to exclude those with diagnoses indicating possible secondary RLS. Those that did not have diagnoses associated with secondary RLS were asked to complete the Cambridge-Hopkins RLS questionnaire to exclude RLS mimics. Prevalence was estimated for the following groups: (1) RLS symptomatic, (2) primary RLS, and (3) primary RLS sufferers (symptoms ≥2/wk with moderate-to-severe distress). The primary RLS completed a larger online survey including the IRLS, EuroQol, Work Productivity and Activity Impairment questionnaire, and questions about healthcare resource use. The validated diagnostic tools and exclusion of medical conditions likely to cause RLS provide a very conservative estimate of US census-weighted prevalence of 2.4% for primary RLS and 1.5% for primary RLS sufferers. About 33% of respondents had a physician diagnosis of RLS. Primary RLS sufferers had a mean productivity loss of 1 day/wk. All RLS-related costs increased with RLS symptom severity, with increasingly significant decrements in health status, sleep disturbance, and work productivity. Even this very conservative approach finds RLS in this cohort to be common, under-diagnosed, and carried a significant personal and social burden.