Cost-effectiveness of avelumab first-line maintenance therapy for adult patients with locally advanced or metastatic urothelial carcinoma in France.

BACKGROUND: This study evaluated the cost-effectiveness of avelumab first-line (1L) maintenance therapy plus best supportive care (BSC) versus BSC alone for adults with locally advanced or metastatic urothelial carcinoma (la/mUC) that had not progressed following platinum-based chemotherapy in France. METHODS: A three-state partitioned survival model was developed to assess the lifetime costs and effects of avelumab plus BSC versus BSC alone. Data from the phase 3 JAVELIN Bladder 100 trial (NCT02603432) were used to inform estimates of clinical and utility values considering a 10-year time horizon and a weekly cycle length. Cost data were estimated from a collective perspective and included treatment acquisition, administration, follow-up, adverse event-related hospitalization, transport, post-progression, and end-of-life costs. Health outcomes were measured in quality-adjusted life-years (QALYs) and life-years gained. Costs and clinical outcomes were discounted at 2.5% per annum. Incremental cost-effectiveness ratios (ICERs) were used to compare cost-effectiveness and willingness to pay in France. Uncertainty was assessed using a range of sensitivity analyses. RESULTS: Avelumab plus BSC was associated with a gain of 2.49 QALYs and total discounted costs of €136,917; BSC alone was associated with 1.82 QALYs and €39,751. Although avelumab plus BSC was associated with increased acquisition costs compared with BSC alone, offsets of -€20,424 and -€351 were observed for post-progression and end-of-life costs, respectively. The base case analysis ICER was €145,626/QALY. Sensitivity analyses were consistent with the reference case and showed that efficacy parameters (overall survival, time to treatment discontinuation), post-progression time on immunotherapy, and post-progression costs had the largest impact on the ICER. CONCLUSIONS: This analysis demonstrated that avelumab plus BSC is associated with a favorable cost-effectiveness profile for patients with la/mUC who are eligible for 1L maintenance therapy in France.

Treatment patterns and clinical outcomes in metastatic urothelial carcinoma: a German retrospective real-world analysis.

Aim: This study assessed real-world treatment in patients with metastatic urothelial carcinoma (mUC) in Germany. Materials & methods: Patients diagnosed with mUC from 2015 to 2019 were identified in two claims databases: AOK PLUS and GWQ. Results: 3226 patients with mUC were analyzed; 1286 (39.9%) received systemic treatment within 12 months of diagnosis (platinum-based chemotherapy: 64.2%). Factors associated with receiving treatment were: younger age, male sex, less comorbidity and recent diagnosis. In AOK PLUS and GWQ populations, unadjusted median overall survival (interquartile range) from diagnosis in treated patients was 13.7 (6.8-32.9) and 13.8 (7.1-41.7) months, and in untreated patients was 3.0 (1.2-10.8) and 3.6 (1.2-18.8) months, respectively. Conclusion: A significant proportion of patients with mUC in Germany receive no systemic treatment.

What is this article about? This article reports the results from a study in Germany between 2015 and 2019 that investigated how advanced bladder cancer that has spread to other organs was treated and how long people lived after diagnosis. The study looked at systemic therapies, which means treatments that affect the entire body. What were the results? Only 40% of people diagnosed with advanced bladder cancer received systemic treatment within the first 12 months. Of those who did receive systemic treatment, the majority received combination therapy that included a chemotherapy drug containing platinum (64%). Systemic treatment was more likely to be given to people who were younger, less sick, male, or more recently diagnosed. After 12 months, 56% of treated people were still alive, compared with 26% of people without treatment. On average, people who received systemic treatment lived for about 14 months, while people without systemic treatment lived for only 3 to 4 months. What do the results of the study mean? Many people with advanced bladder cancer in Germany do not receive systemic treatment. People who receive treatment are likely to live longer than those who do not receive treatment.

Healthcare resource utilization and associated costs in patients with metastatic urothelial carcinoma: a real-world analysis using German claims data.

AIMS: This retrospective claims data study characterized real-world treatment patterns, healthcare resource utilization (HCRU), and costs in patients with metastatic urothelial carcinoma (mUC) in Germany. MATERIALS AND METHODS: Continuously insured adults with incident mUC diagnosis (=index; ICD-10: C65-C68/C77-C79) in 2015-2019 were identified from two German claims databases. Patients who received first-line (1 L) treatment within 12 months of index were divided into three mutually exclusive sub-cohorts: platinum-based chemotherapy (PB-CT), non-PB-CT, and immunotherapy (IO). Patient characteristics were assessed during a 24-month baseline period; treatments, HCRU, and costs (of the health insurance fund) per patient-year (ppy) were described during 12-month follow-up. RESULTS: We identified 3,226 patients with mUC (mean age, 73.8 years; male, 70.8%; mean Elixhauser Comorbidity Index, 17.6); 1,286 (39.9%) received 1 L treatment within 12 months of index. Of these, 825 (64.2%) received PB-CT, 322 (25.0%) non-PB-CT, and 139 (10.8%) IO. On average, treated patients had 5.1 hospitalizations ppy. Most UC-related hospitalizations ppy were observed in the PB-CT cohort (5.8), followed by the non-PB-CT (4.2) and IO (2.3) cohorts. Mean UC-related hospitalization costs ppy were €22,218 in the treated cohort, €24,294 in PB-CT, €19,079 in IO, and €18,530 in non-PB-CT cohorts. Cancer-related prescription costs ppy averaged €6,323 in treated patients, and €25,955 in IO, €4,318 in non-PB-CT, and €4,270 in PB-CT cohorts. LIMITATIONS: We recognized limitations in our study's sample selection due to unavailable mUC disease status data. We addressed this through an upstream feasibility study conducted in consultation with clinical experts to determine a suitable proxy. Proxies were also used to delineate treatment lines, switches, and discontinuations due to data absence. Furthermore, due to data restrictions, collective dataset analysis was not possible, prompting a meta-analysis for pooled results. CONCLUSIONS: The study shows that mUC is associated with significant HCRU and costs across different types of 1 L systemic therapy.

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.

Treatment patterns in metastatic bladder cancer in Japan: results of the CancerMPact® survey 2020.

Aim: To assess physician-reported treatment of metastatic bladder cancer in Japan. Methods: 76 physicians completed the CancerMPact® survey in July 2020, considering patients treated within 6 months. Results: Physicians treated a mean of 38.1 patients per month. Of cisplatin-eligible and -ineligible patients, 97.6 and 89.3%, respectively, received first-line platinum-based therapy, most commonly cisplatin plus gemcitabine (72.9%) and carboplatin plus gemcitabine (59.7%). 1.6 and 5.6% received first-line immune checkpoint inhibitors, respectively. 48.4 and 45.0%, respectively, progressed and received second-line therapy, most commonly with pembrolizumab (61.7%). Conclusion: In 2020, most patients with metastatic bladder cancer in Japan received first-line platinum-based chemotherapy; however, >50% received no subsequent treatment, highlighting the need for new treatment regimens to improve outcomes and maximize first-line treatment benefits.

In 2020, researchers surveyed 76 Japanese doctors who specialized in bladder and urinary system disorders about how they treated people with bladder cancer. Cisplatin, a type of chemotherapy drug, was the most common first treatment. For people who were unable to receive cisplatin, doctors often prescribed a similar chemotherapy drug called carboplatin. Just under half of the people received a second treatment for their cancer. New treatments are now available for bladder cancer, including the immunotherapy drug avelumab, which is given to people whose cancer stops growing or shrinks with their first chemotherapy treatment. More research is needed to better understand how bladder cancer is treated in Japan, including how new treatments are used.

Cost-effectiveness analysis for avelumab first-line maintenance treatment of advanced urothelial carcinoma in Scotland.

Aim: The cost-effectiveness of avelumab first-line maintenance treatment for locally advanced or metastatic urothelial carcinoma in Scotland was assessed. Materials & methods: A partitioned survival model was developed comparing avelumab plus best supportive care (BSC) versus BSC alone, incorporating JAVELIN Bladder 100 trial data, costs from national databases and published literature and clinical expert validation of assumptions. Incremental cost-effectiveness ratio (ICER) was estimated using lifetime costs and quality-adjusted life-years (QALY). Results: Avelumab plus BSC had incremental costs of £9446 and a QALY gain of 0.63, leading to a base-case (deterministic) ICER of £15,046 per QALY gained, supported by robust sensitivity analyses. Conclusion: Avelumab first-line maintenance is likely to be a cost-effective treatment for locally advanced or metastatic urothelial carcinoma in Scotland.

What is this article about? This study looked at the costs of avelumab when given as maintenance treatment for people in Scotland with advanced urothelial carcinoma, compared with the longer survival and other benefits that it provides. How was this done? Researchers estimated the costs and treatment benefits expected with avelumab using data from a clinical trial called JAVELIN Bladder 100, national databases, data from previously published studies and expert opinions. What were the results? Costs associated with using avelumab maintenance treatment for people with advanced urothelial carcinoma in Scotland were considered to be acceptable based on the benefits it provides. What do the results of the study mean? These results support the use of avelumab first-line maintenance as a standard treatment for people with advanced urothelial carcinoma in Scotland.

Physician reported treatment patterns and outcomes in metastatic bladder cancer in the USA: the CancerMPact® Survey 2020.

Aim: This study assessed physician-reported treatment patterns for metastatic bladder cancer. Materials & methods: A total of 106 USA-based physicians were surveyed in 2020 using the CancerMPact® online survey. Results: Among cisplatin-eligible patients, 86.1% received first-line (1L) platinum-containing chemotherapy, most commonly cisplatin plus gemcitabine, and 9.8% received immune checkpoint inhibitor monotherapy. Among cisplatin-ineligible patients, 46.5% received 1L platinum-containing chemotherapy, most commonly carboplatin plus gemcitabine and 46.2% received 1L immune checkpoint inhibitor therapy. Approximately 44% of patients who received 1L treatment received second-line (2L) therapy after progression. Conclusion: Platinum-containing chemotherapy was the most widely reported 1L treatment approach. A high proportion of patients received no 2L therapy. Validation in an updated dataset is warranted following the practice-changing approvals of avelumab 1L maintenance and additional 2L options.

In 2020, researchers surveyed 106 US doctors about how they treated people with advanced bladder cancer. Cisplatin, a chemotherapy drug, was the most common first treatment that was given to patients with advanced bladder cancer. For people who were unable to receive cisplatin, doctors preferred to prescribe a similar chemotherapy drug called carboplatin or an immunotherapy drug. Immunotherapies help the body's immune system to fight cancer cells. Most people treated by the surveyed doctors did not receive a second treatment if their cancer got worse. New treatments are now available for bladder cancer, such as the immunotherapy, avelumab. Avelumab is given after chemotherapy to try and stop the cancer from getting worse or coming back. More research is needed to further understand how bladder cancer is treated.

Real-World Analysis of Treatment Patterns and Platinum-Based Treatment Eligibility of Patients With Metastatic Urothelial Cancer in 5 European Countries.

INTRODUCTION: The global treatment landscape for metastatic urothelial cancer (mUC) is evolving, with the recent approval of several new therapeutics. To enable informed treatment decisions, a need exists to understand both treatment patterns and how physicians determine platinum-based treatment eligibility status. This study investigated physicians' current approaches to first-line (1L) chemotherapy, treatment patterns, and assessment of platinum-based treatment eligibility of patients with mUC in real-world clinical practice. PATIENTS AND METHODS: Data were derived from the Adelphi mUC Disease Specific Programme™, a large, independent, multinational, cross-sectional survey of physicians and their consulting patients with mUC presenting in a real-world clinical setting, conducted in France, Germany, Italy, Spain, and the United Kingdom between November 2020 and April 2021. Physicians completed record forms for their next 8 consecutively consulting patients (≤3 1L, ≤2 second-line, and ≤3 third-line) with a physician-confirmed diagnosis of mUC, reporting data on demographics, clinical characteristics, eligibility for platinum-based chemotherapy, and treatments received. RESULTS: Overall, 232 physicians provided data for 1922 patients. Renal function impairment (72%), Eastern Cooperative Oncology Group performance status (59%), and age (38%) were the most commonly reported criteria physicians used to determine eligibility for platinum-based chemotherapy. At 1L, 82% of patients received platinum-based chemotherapy (cisplatin, 51%; carboplatin, 31%) and 10% received immune checkpoint inhibitor (ICI) therapy. At second-line, 12% received platinum-based chemotherapy, 63% ICI therapy, and 21% non-platinum-based chemotherapy. At third-line, 4% received platinum-based chemotherapy, 41% best supportive care only, and 36% other non-platinum-based chemotherapy. CONCLUSIONS: The results of this real-world study indicate that in accordance with European guidelines, the majority of patients with mUC received standard-of-care 1L platinum-based chemotherapy and use of ICIs was limited. Future research should assess how physicians' perceptions toward determining platinum eligibility status evolve with newer guideline recommendations and the introduction of new therapy options for mUC.

Nationwide Study of Real-World Treatment Patterns and Clinical Outcomes in Patients with Metastatic Urothelial Carcinoma in Hungary.

INTRODUCTION: Data describing real-world treatment patterns in patients with metastatic urothelial carcinoma (mUC) in Central-Eastern Europe are scarce, and data from Hungary have not been published. This retrospective, nationwide, real-world study investigated patient characteristics, treatment patterns, comorbidities, and clinical outcomes in patients with mUC in Hungary. METHODS: Adults diagnosed with mUC from January 2016 through June 2021 were identified using the National Health Insurance Fund Administration database. Overall survival (OS) was estimated using the Kaplan-Meier method. RESULTS: In total, 2523 patients with mUC were identified. Median follow-up was 7.1 months. Overall, 50% of patients received an identified systemic anticancer treatment; within this subgroup, first-line treatment was platinum-based chemotherapy (PBC) in 86%, non-PBC in 8%, and immune checkpoint inhibitor (ICI) in 6%. The proportion of patients receiving treatment increased from 41% in 2016 to 59% in 2020, driven by increased use of first-line PBC or first-line ICI treatment. Comorbidities were more common in patients receiving first-line ICI treatment vs PBC or non-PBC and in patients receiving carboplatin + gemcitabine vs cisplatin + gemcitabine. Overall, only 24% received a second-line treatment. Unadjusted median OS from the start of first-line treatment in the PBC, non-PBC, and ICI subgroups was 12.8, 7.5, and 6.3 months, respectively. Median OS from date of diagnosis in untreated patients was 7.8 months. OS comparisons adjusted for differences in baseline characteristics between subgroups could not be performed. CONCLUSION: To our knowledge, this is the first study to assess treatment patterns in patients with mUC in clinical practice in Hungary, using the national health insurance database. Rates of first- and second-line treatment were consistent with those observed in other countries. Avelumab first-line maintenance treatment became available for reimbursement in Hungary in late 2022, after the study period. Given the evolving landscape of reimbursed treatments in Hungary, further analyses are warranted.

Undertreatment in patients with advanced urothelial cancer: systematic literature review and meta-analysis.

Aim: To assess rates of no systemic treatment (NST), attrition across lines of therapy, and factors influencing treatment selection in patients with locally advanced or metastatic urothelial cancer (la/mUC). Methods: Systematic literature review to identify real-world studies reporting NST or attrition rates in la/mUC from 2017-2022 (including data reported since 2015). Results: Of 2439 publications screened, 29 reported NST rates, ranging from 40-74% in eight European-based studies, 14-60% in 12 US-based studies, and 9-63% in nine studies in other locations (meta-analysis estimate, 39%). Factors associated with NST or no second-line therapy included older age, female sex, poor performance status, poor renal function and distant metastases. Conclusion: A substantial proportion of patients with la/mUC do not receive guideline-recommended treatment.

People with advanced bladder cancer have a short survival. Bladder cancer is called advanced when it has spread outside of the urinary tract. Several drug treatments are available for people with advanced bladder cancer. However, sometimes people do not receive any drug treatment. We looked at published studies to see how many people with advanced bladder cancer did not receive any drug treatment and the reasons why. We also looked at how long people lived with or without drug treatment. We found that many people with advanced bladder cancer did not receive drug treatment. The number of people who received no drug treatment varied in studies from different countries. People who were older, were female, had poor health or kidney problems, or had cancer that had spread to other parts of the body were less likely to receive drug treatment. People who did not receive drug treatment lived for an average of 2 to 7 months, compared with 9 to 35 months for people who received drug treatment. More studies are needed to investigate the reasons why drug treatment is sometimes not used in people with advanced bladder cancer who could receive treatment, so that more people can benefit from available treatments.

A cost-effectiveness analysis of avelumab plus best supportive care versus best supportive care alone as first-line maintenance treatment for patients with locally advanced or metastatic urothelial carcinoma in Taiwan.

BACKGROUND: Patients with locally advanced or metastatic urothelial carcinoma have limited treatment options and a poor prognosis. The JAVELIN Bladder 100 trial showed that avelumab as first-line maintenance plus best supportive care significantly prolonged overall survival and progression-free survival versus best supportive care alone in patients with locally advanced or metastatic urothelial carcinoma that had not progressed with first-line platinum-containing chemotherapy. AIMS: We assessed whether avelumab plus best supportive care is a cost-effective treatment option versus best supportive care alone in this patient group in Taiwan. METHODS AND RESULTS: A partitioned survival model was used to estimate the costs and effects of avelumab plus best supportive care versus best supportive care alone over a 20-year time horizon from the perspective of Taiwan's National Health Insurance Administration. Patient-level data from JAVELIN Bladder 100 on efficacy, safety, utility, and time on treatment were analyzed to provide parameters for the model. Log-normal and Weibull distributions were used for overall survival and progression-free survival, respectively. Costs of healthcare resources, drug acquisition, adverse events, and progression were identified through publicly available data sources and clinician interviews. The model estimated total costs, life years, and quality-adjusted life years. In the modeled base case, avelumab plus best supportive care increased survival versus best supportive care alone by 0.79 life years (2.93 vs. 2.14) and 0.61 quality-adjusted life years (2.15 vs. 1.54). The incremental cost-effectiveness ratio for avelumab plus best supportive care versus best supportive care alone was NT$1 827 680. Most (78%) of the probabilistic sensitivity analyses fell below three times the gross domestic product per capita. Scenario analysis indicated that life year and quality-adjusted life year gains were most sensitive to alternative survival extrapolations for both avelumab plus best supportive care and best supportive care alone. CONCLUSION: Avelumab first-line maintenance therapy combined with best supportive care was determined as a cost-effective treatment strategy for patients in Taiwan diagnosed with locally advanced or metastatic urothelial carcinoma that had not progressed with platinum-containing chemotherapy.

Evaluating Real-World Characteristics of Patients With Advanced Urothelial Carcinoma Eligible for Avelumab Maintenance Therapy: A Multicountry Retrospective Medical Chart Review.

INTRODUCTION: Urothelial carcinoma (UC) is a malignancy of the urothelium that encompasses the renal pelvis, bladder, and urethra. Current treatment guidelines for advanced (ie, locally advanced or metastatic) UC recommend using avelumab maintenance therapy in patients with nonprogressive disease following first-line platinum-based chemotherapy. This study aimed to assess the representativeness of the patient population in the JAVELIN Bladder 100 (JB-100) trial, which examined the efficacy and safety of avelumab first-line maintenance, vs. real-world patients with advanced UC that had not progressed with first-line platinum-based chemotherapy treated between 2015 and 2018 by reviewing demographic and clinical characteristics. PATIENTS AND METHODS: A medical chart review (MCR) study collected demographics and treatment characteristics for patients with advanced UC in the United States, the United Kingdom, and France. Data were analyzed descriptively for review with data collected from patients enrolled in JB-100. RESULTS: Clinical characteristics were consistent between JB-100 and the MCR. Most patients were male, received 4 to 6 cycles of platinum-based chemotherapy, and had an Eastern Cooperative Oncology Group performance status of 0 or 1. All patients in the MCR had either stable disease or a response with platinum-based chemotherapy (∼75% achieved a complete or partial response). Fewer than half (42.5%) of all patients in the MCR received subsequent therapy. CONCLUSION: Patient demographics, clinical characteristics, and treatment patterns from a MCR of patients with advanced UC that had not progressed following first-line platinum-based chemotherapy appeared similar to data from patients enrolled in JB-100. Future studies should examine whether real-world outcomes are consistent with findings from JB-100. GOV IDENTIFIER: NCT02603432.

Real-world symptoms, disease burden, resource use and quality of life in US patients with advanced renal cell cancer.

Aim: To assess symptoms, healthcare resource utilization and health-related quality of life in advanced renal cell carcinoma (aRCC) clinical practice. Materials & methods: The USA point-in-time survey of physicians and patients was conducted between February and September 2019. Results: Data were available for 227 patients. Mean (standard deviation) number of symptoms was 3.4 (3.2); differences were observed across International Metastatic RCC Database Consortium risk categories (p < 0.001), with fewer symptoms in favorable-risk patients. Disease burden, measured by greater healthcare resource utilization and worse health-related quality of life, was high, particularly in International Metastatic RCC Database Consortium intermediate- or poor- versus favorable-risk patients. In total, 45 patients (21.6%) were hospitalized due to aRCC within a 6-month period, 35 (16.8%) had one hospitalization and ten (4.8%) experienced ≥2 hospitalizations due to aRCC. Mean (standard deviation) 19-Item Functional Assessment of Cancer Therapy Kidney Symptom Index score was 53.6 (13.2) for this population, significantly lower than the reference value (59.8; p < 0.001). Conclusion: A clear need exists for improved disease management in patients with aRCC.

Lay abstract Late-stage/advanced renal cell carcinoma (aRCC) is kidney cancer that has spread to other body parts. aRCC is expensive to treat and affects patients in many ways. New treatments have become available, including tyrosine kinase inhibitors and immuno-oncology therapies. The type of treatment recommended depends on the patient's International Metastatic RCC Database Consortium risk score. This is a way of classifying patients as having a good, intermediate or poor survival risk. We asked physicians questions about their patients such as their age, how long they had aRCC, their treatment and symptoms, and asked patients how aRCC affected their lives, including how often they visited doctors and hospitals. aRCC had the greatest effect on patients with poor-risk scores. Those patients had more symptoms and worse quality of life than patients with intermediate or good risk scores. Treatment also affected patients' lives, although not as much as risk score. Patients with aRCC need better treatment options to help improve their quality of life.

Treatment Sequencing Patterns in Patients with Metastatic Urothelial Cancer Treated in the Community Practice Setting in the United States: SPEAR-Bladder (Study informing treatment Pathway dEcision in bladder cAnceR).

PURPOSE: 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.

Real-world outcomes among US Merkel cell carcinoma patients initiating immune checkpoint inhibitors or chemotherapy.

Aim: Retrospectively assessed treatment patterns and clinical and economic outcomes in Merkel cell carcinoma (MCC) patients receiving recommended first-line regimens. Materials & methods: MCC patients newly treated with either immune checkpoint inhibitors (ICIs) or chemotherapies (CTs) were selected from the Veterans Health Administration database (2013-2018); 74 patients (ICIs: 20 and CTs: 54) were selected. Results: Median duration of therapy was 300 days for ICIs and 91 days for CTs. Time to next treatment was 245 and 184 days, respectively. Mean total (per patient per month) costs were $15,306 (ICIs) and $10,957 (CTs), of which 51% and 86%, respectively, were non-MCC therapy-related costs. Conclusion: Despite higher costs, utilization of ICIs in first-line MCC shows clinical advantages over CTs in the real world.

Treatment patterns, outcomes and clinical characteristics in advanced renal cell carcinoma: a real-world US study.

Aim: Assessing treatment patterns, outcomes and clinical characteristics in advanced renal cell carcinoma clinical practice. Materials & methods: A US cross-sectional physician survey conducted February-September 2019. Results: Surveyed physicians reported first-line treatment of 445 patients involving tyrosine kinase inhibitor monotherapy (51.0%), immuno-oncology (IO/IO combination) therapy (25.8%) or other regimens (23.1%). A total of 60.9% had physician-assessed IMDC risk. Of these 61.9, 50.9 and 27.6% of patients with favorable, intermediate and poor risk, respectively, received tyrosine kinase inhibitor monotherapy. A total of 16.7, 26.9 and 34.5% of patients with favorable, intermediate or poor risk received IO/IO combination therapy. Complete/partial responses (∼35% patients) remained comparable across first-line treatments. Conclusion: Guideline-recommended therapies are not widely prescribed. Many patients experienced poor clinical outcomes highlighting a need for more effective treatments.

Budget Impact Of Including Avelumab As A Second-Line Treatment For Locally Advanced Or Metastatic Urothelial Cancer In The United States: Commercial And Medicare Payer Perspectives.

OBJECTIVE: 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.

Assessment-Schedule Matching in Unanchored Indirect Treatment Comparisons of Progression-Free Survival in Cancer Studies.

BACKGROUND: 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. OBJECTIVE: 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. METHODS: 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). RESULTS: 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. CONCLUSIONS: 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.

Budget impact model of avelumab in patients with metastatic merkel cell carcinoma in the US.

Objective: To estimate the budget impact of avelumab as a treatment option for patients with treatment-naïve first-line (1L) and previously treated second-line or later (2L+) metastatic Merkel cell carcinoma (mMCC) in the US. Methods: A budget impact model was developed to evaluate the addition of avelumab for the treatment of mMCC patients using a hypothetical 30 million-member US health plan over a 3-year time horizon (2019-2021). The comparator treatments included in the analysis were pembrolizumab and nivolumab (other immuno-oncology agents); and the chemotherapies routinely used in the eligible mMCC population. Model inputs included market share uptake of avelumab and other comparators, duration of treatments, and costs (drugs, health care resource utilization, adverse events). The model was evaluated from a commercial payer perspective. Sensitivity analyses were conducted to test uncertainties arising from the input values used in the model. Results: In a hypothetical commercial health plan of 30 million members, 285 patients with mMCC were identified over 3 years; 43 patients received avelumab as a 1L treatment over 3 years. In a world without avelumab, the total health care costs of treating patients with mMCC over 3 years were estimated to be US$11,710,115 from a commercial health plan perspective. With avelumab, there were estimated savings of $2,643,173 considering the total costs related to the treatment of mMCC over 3 years (23% reduction in the budget). The incremental cost per member per month over 3 years was -$0.0025. Conclusion: The model results indicate that the adoption of avelumab as a treatment option for mMCC would likely result in minimal budget impact from a US health plan perspective. Patients with mMCC, a rare condition with a poor prognosis and high unmet need, may benefit greatly from recently approved immunotherapies.