Real-world evidence in the reassessment of oncology therapies: payer perceptions from five countries.

Aim: This study explored the perceived value of real-world evidence (RWE) in the reassessment of oncology therapies by collecting the perspectives of health technology assessment/payer decision-makers.Materials & methods: A web-based survey was conducted using the Market Access Transformation Rapid Payer Response online portal. 30 participants from France, Germany, Spain, the UK and the USA were recruited based on their expertise.Results: Participants agreed that the most common uses of RWE are to confirm efficacy and safety results from randomized controlled trials and to reevaluate the projected utilization of an oncology therapy. We found variability in other reported uses of RWE.Conclusion: The organizations developing RWE should ensure that their plans recognize the heterogeneity in payer perceptions.

A survey from the Market Access Transformation RPR portal queried decision-makers from five countries about the value of real-world evidence in oncology therapy reassessment. Participants agreed that RWE can confirm efficacy/safety and reevaluate utilization, but other uses varied.

Preferences for first-line treatment of advanced urothelial carcinoma among US practicing oncologists and patients.

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.

Different treatments are available for people with urothelial cancer that has spread to other parts of the body. Researchers wanted to find out what specialist cancer doctors and people with urothelial cancer think is important when choosing the first treatment. To do this, researchers asked 150 cancer specialists and 150 people with urothelial cancer to complete an internet questionnaire. It included questions about side effects, if treatment could help people live longer, and how often people would need to be treated. Researchers found that cancer specialists think that helping people live longer is the most important. However, people with advanced urothelial cancer think that having fewer severe side effects is the most important.

How Assessment-Schedule Matching Limits Bias When Comparing Progression-Free Survival in Single-Arm Studies: An Application in Second-Line Urothelial Carcinoma Treatments.

OBJECTIVES: Population-adjusted comparisons of progression-free survival (PFS) from single-arm trials of cancer treatments can be derived using matching-adjusted indirect comparisons (MAICs); however, results are still susceptible to bias, particularly if the trials had different tumor assessment schedules. This study aims to assess the effects of assessment-schedule matching (ASM) on the relative effectiveness on the PFS of avelumab versus approved comparator immunotherapies or chemotherapy after population matching in the second-line (2L) setting for metastatic urothelial carcinoma. METHODS: The MAIC used patient-level data for avelumab from the JAVELIN Solid Tumor trial (NCT01772004). PFS was compared with published curves for other treatments to obtain population-adjusted hazard ratios (HRs). The MAIC was repeated after conducting ASM for differences in tumor assessment scheduled first at 6 weeks for avelumab and durvalumab and at 8 or 9 weeks for other treatments. RESULTS: MAIC adjustment alone altered the HR estimates up to 23%, whereas MAIC plus ASM resulted in up to 32.7% reductions from naive comparisons. Even in cases in which MAIC had little effect, ASM brought an additional change of 11.1% to 15.4%. Overall, the HR range of avelumab versus other treatments changed from 0.83 to 1.25 for naive comparisons to 0.76 to 0.99 after ASM plus MAIC, numerically favoring avelumab. CONCLUSIONS: Small variations in assessment schedules can introduce bias in unanchored indirect treatment comparisons of interval-censored time-to-event outcomes. In this study, adjusted PFS was comparable across second-line urothelial carcinoma treatment options, numerically favoring avelumab versus immunotherapies and chemotherapy agents. Correcting this bias is especially important when HRs are applied in cost-effectiveness models to transition patients between states.

Systematic literature review of current treatments for stage I-III Merkel cell carcinoma.

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.

Evaluation of survival extrapolation in immuno-oncology using multiple pre-planned data cuts: learnings to aid in model selection.

BACKGROUND: Due to limited duration of follow up in clinical trials of cancer treatments, estimates of lifetime survival benefits are typically derived using statistical extrapolation methods. To justify the method used, a range of approaches have been proposed including statistical goodness-of-fit tests and comparing estimates against a previous data cut (i.e. interim data collected). In this study, we extend these approaches by presenting a range of extrapolations fitted to four pre-planned data cuts from the JAVELIN Merkel 200 (JM200) trial. By comparing different estimates of survival and goodness-of-fit as JM200 data mature, we undertook an iterative process of fitting and re-fitting survival models to retrospectively identify early indications of likely long-term survival. METHODS: Standard and spline-based parametric models were fitted to overall survival data from each JM200 data cut. Goodness-of-fit was determined using an assessment of the estimated hazard function, information theory-based methods and objective comparisons of estimation accuracy. Best-fitting extrapolations were compared to establish which one provided the most accurate estimation, and how statistical goodness-of-fit differed. RESULTS: Spline-based models provided the closest fit to the final JM200 data cut, though all extrapolation methods based on the earliest data cut underestimated the 'true' long-term survival (difference in restricted mean survival time [RMST] at 36 months: - 1.1 to - 0.5 months). Goodness-of-fit scores illustrated that an increasingly flexible model was favored as data matured. Given an early data cut, a more flexible model better aligned with clinical expectations could be reasonably justified using a range of metrics, including RMST and goodness-of-fit scores (which were typically within a 2-point range of the statistically 'best-fitting' model). CONCLUSIONS: Survival estimates from the spline-based models are more aligned with clinical expectation and provided a better fit to the JM200 data, despite not exhibiting the definitively 'best' statistical goodness-of-fit. Longer-term data are required to further validate extrapolations, though this study illustrates the importance of clinical plausibility when selecting the most appropriate model. In addition, hazard-based plots and goodness-of-fit tests from multiple data cuts present useful approaches to identify when a more flexible model may be advantageous. TRIAL REGISTRATION: JAVELIN Merkel 200 was registered with ClinicalTrials.gov as NCT02155647 on June 4, 2014.

Update on the psychometric properties and minimal important difference (MID) thresholds of the FACT-M questionnaire for use in treatment-naïve and previously treated patients with metastatic Merkel cell carcinoma.

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.

Health-related quality of life trajectory of treatment-naive patients with Merkel cell carcinoma receiving avelumab.

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).

Early objective response to avelumab treatment is associated with improved overall survival in patients with metastatic Merkel cell carcinoma.

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.

Psychometric Properties of EQ-5D-5L Scoring Algorithms for the United Kingdom in Metastatic Merkel Cell Carcinoma.

BACKGROUND: Currently, there are 4 EQ-5D-5L scoring algorithms available for the United Kingdom that can be used to derive a utility score. OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Correction to: Psychometric properties of the FACT-M questionnaire in patients with Merkel cell carcinoma.

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Nonprogression with avelumab treatment associated with gains in quality of life in metastatic Merkel cell carcinoma.

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.

Using Response Evaluation Criteria in Solid Tumors in real-world evidence cancer research.

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.

Psychometric properties of the FACT-M questionnaire in patients with Merkel cell carcinoma.

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 .

Real-world treatment outcomes in patients with metastatic Merkel cell carcinoma treated with chemotherapy in the USA.

AIM: This retrospective study of patients in the USA with metastatic Merkel cell carcinoma (mMCC) aimed to assess patient responses to second-line and later (2L+) and first-line (1L) chemotherapy. PATIENTS & METHODS: Out of 686 patients with MCC identified in The US Oncology Network, 20 and 67 patients with mMCC qualified for the 2L+ and 1L study, respectively; the primary analysis population was restricted to immunocompetent patients. RESULTS: In the 2L+ primary analysis population, objective response rate (ORR) was 28.6%, median duration of response (DOR) was 1.7 months and median progression-free survival was 2.2 months. In the 1L primary analysis population, ORR was 29.4%, median DOR was 6.7 months and median progression-free survival was 4.6 months. CONCLUSION: The low ORR and brief DOR underscore the need for novel therapies.

Systematic literature review of efficacy, safety and tolerability outcomes of chemotherapy regimens in patients with metastatic Merkel cell carcinoma.

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.

Understanding Clinician Preferences for Treatment Attributes in Oncology: A Discrete Choice Experiment of Oncologists' and Urologists' Preferences for First-Line Treatment of Locally Advanced/Unresectable Metastatic Urothelial Carcinoma in Five European Countries.

INTRODUCTION: Prior discrete choice experiments (DCE) in oncology found that, on average, clinicians rank survival as the most important treatment attribute. We investigate heterogeneity in clinician preferences within the context of first-line treatment for advanced urothelial carcinoma in Spain, France, Italy, Germany, and the UK. METHODS: The online DCE included 12 treatment choice tasks, each comparing two hypothetical therapy profiles defined by treatment attributes: grade 3/4 treatment-related adverse events (TRAEs), induction and maintenance administration schedules, progression-free survival, and overall survival (OS). We used a random parameters logit model to estimate attribute relative importance (RI) (0-100%) and generate preference shares for four treatment profiles. Results were stratified by country. Preference heterogeneity was evaluated by latent class analysis. RESULTS: In August and September 2022, 498 clinicians (343 oncologists and 155 urologists) completed the DCE. OS had the strongest influence on clinicians' preferences [RI = 62%; range, 51.6% (Germany) to 63.7% (Spain)] followed by frequency of grade 3/4 TRAEs (RI = 27%). Among treatment profiles, the chemotherapy plus immune checkpoint inhibitor maintenance therapy profile had the largest preference share [51%; range, 38% (Italy) to 56% (UK)]. Four latent classes of clinicians were identified (N = 469), with different treatment profile preferences: survival class (30.1%), trade-off class (22.4%), no strong preference class (40.9%), and aggressive treatment class (6.6%). OS was not the most important attribute for 30.0% of clinicians. CONCLUSION: While average sample results were consistent with those of prior DCEs, this study found heterogeneity in clinician preferences within and across countries, highlighting the diversity in clinician decision making in oncology.

Patient and Caregiver Perceptions of Advanced Bladder Cancer Systemic Treatments: Infodemiology Study Based on Social Media Data.

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.

Incremental dementia-related expenditures in a medicaid population.

OBJECTIVES: With the growing number of older adults, understanding expenditures associated with treating medical conditions that are more prevalent among older adults is increasingly important. The objectives of this research were to estimate incremental medical encounters and incremental Medicaid expenditures associated with dementia among Indiana Medicaid recipients 40 years or older in 2004. METHODS: A retrospective cohort design analyzing Indiana Medicaid administrative claims files was used. Individuals at least 40 years of age with Indiana Medicaid eligibility during 2004 were included. Patients with dementia were identified via diagnosis codes in claims files between July 2001 and December 2004. Adjusted annual incremental medical encounters and expenditures associated with dementia in 2004 were estimated using negative binomial regression and zero-inflated negative binomial regression models. RESULTS: A total of 18,950 individuals (13%) with dementia were identified from 145,684 who were 40 years or older. The unadjusted mean total annualized Medicaid expenditures for the cohort with dementia ($28,758) were significantly higher than the mean expenditures for the cohort without dementia ($14,609). After adjusting for covariates, Indiana Medicaid incurred annualized incremental expenditures of $9,829 per recipient with dementia. Much of the annual incremental expenditure associated with dementia was driven by the higher number of days in nursing homes and resulting nursing-home expenditures. Drug expenditures accounted for the second largest component of the incremental expenditures. On the basis of disease prevalence and per recipient annualized incremental expenditures, projected incremental annualized Indiana Medicaid spending associated with dementia for persons 40 or more years of age was $186 million. CONCLUSIONS: Dementia is associated with significant expenditures among Medicaid recipients. Disease management initiatives designed to reduce nursing-home use among recipients with dementia may have much potential to decrease Medicaid expenditures associated with dementia.

Management of Patients With Advanced Urothelial Carcinoma in an Evolving Treatment Landscape: A Qualitative Study of Provider Perspectives of First-Line Therapies.

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.

Real-world clinical outcomes with avelumab in patients with Merkel cell carcinoma treated in the USA: a multicenter chart review study.

BACKGROUND: Merkel cell carcinoma (MCC) is a rare, aggressive, cutaneous neuroendocrine neoplasm with annual incidence rates of 0.13-1.6 cases/100,000/year worldwide as of 2018. Chemotherapy for metastatic MCC (mMCC) has high objective response rates (ORRs), but responses are not durable and overall survival (OS) is poor. Avelumab (anti-programmed death-ligand 1) has demonstrated meaningful survival benefit and durable responses in clinical trials for mMCC. This study investigated real-world clinical outcomes in avelumab-treated patients with advanced (stage IIIB/IV) MCC in US academic medical centers. METHODS: We conducted a retrospective chart review of patients with advanced MCC who initiated avelumab between March 1, 2017, and July 31, 2019, at six US academic centers. Data were requested for eligible patients from index date through December 31, 2020. Descriptive analyses were conducted to assess demographic and clinical characteristics, real-world ORR (rwORR), real-world duration of response, real-world progression-free survival (rwPFS), and OS. RESULTS: Ninety patients with advanced MCC (82%, stage IV; 18%, stage IIIB) received avelumab. Median follow-up was 20.8 months (95% CI: 19.1 to 24.2). Median age was 68 years (range, 48-83), and the majority of patients were men (58%) and white (93%). The primary tumor was most commonly located on the lower limb (38%), with metastases mostly located in lymph nodes (68%), lung (52%), and viscera (52%). Approximately 42% and 26% of patients had an Eastern Cooperative Oncology Group performance status of 2 and 3, respectively. Seventy-three patients (81%) received avelumab as first-line treatment of advanced MCC, while 17 (19%) received avelumab as second-line or later treatment. The median duration of avelumab treatment was 13.5 months (95% CI: 6.4 to 30.6), with 42% of patients still receiving avelumab by the end of follow-up. Patients with avelumab treatment had an rwORR of 73% (95% CI: 64 to 83), median rwPFS of 24.4 months (95% CI: 8.31 to not estimable (NE)), and median OS of 30.7 months (95% CI: 11.2 to NE). CONCLUSIONS: This real-world study of patients with advanced MCC demonstrated that avelumab treatment resulted in a high response rate with durable responses and prolonged survival. The study findings validate the results demonstrated in prospective clinical trials and other observational studies.