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Direct costs associated with adverse events of systemic therapies for advanced melanoma: Systematic literature review.

ABSTRACT: Treatments for advanced melanoma are associated with different adverse events (AEs), which may be costly to manage. This study aimed to evaluate direct costs associated with managing treatment-related AEs for advanced melanoma through a systematic literature review.Systematic searches were conducted of the PubMed, Embase, Cochrane, BIOSIS, and EconLit medical literature databases to identify studies providing estimates of direct costs and health care resource utilization for the management of AEs of melanoma treatments, published between January 1, 2007, and February 23, 2017. Gray literature searches also were conducted. Studies reporting direct costs for patients with advanced melanoma that were published in English between 2007 and 2017 were eligible. Studies were systematically screened in 2 phases by 2 independent reviewers. Study design details and data on direct costs by country were extracted.Seven studies evaluating the cost of AEs in patients with advanced melanoma were included; most estimated the costs for grade 3 or 4 events. In a United States study, monthly AE costs constituted 36.9% of overall health care costs for dacarbazine, 30.3% for paclitaxel, 9.2% for temozolomide, 6.4% for vemurafenib, and 4.0% for ipilimumab. A multicountry study found the greatest cost per event to be for grade 3 or 4 AEs associated with ipilimumab, including colitis (A$1471 [Australia]-&OV0556;3313 [France]) and diarrhea (£2836 [United Kingdom]), and chemotherapy (neutropenia/leukopenia in Germany [&OV0556;1744] and Italy [&OV0556;804]). Across studies, cost drivers for the most expensive AEs to manage were requiring hospitalization or use of expensive outpatient medications and/or procedures (eg, erythropoietin and blood transfusions for anemia). Some currently available therapies were not available during the research period, and their associated AEs are not reflected. Results may not be comparable across countries. For some studies, resource-use estimates reflect practice patterns from a limited number of centers, limiting generalizability.Costs for managing each type of AE associated with the treatment of advanced melanoma are substantial. Effective treatments with improved safety profiles may help reduce total AE management costs.

SUBMITTER: Copley-Merriman C

PROVIDER: S-EPMC6081130 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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Direct costs associated with adverse events of systemic therapies for advanced melanoma: Systematic literature review.

Copley-Merriman Catherine C Stevinson Kendall K Liu Frank Xiaoqing FX Wang Jingshu J Mauskopf Josephine J Zimovetz Evelina A EA Chmielowski Bartosz B

Medicine 20180801 31

<h4>Background</h4>Treatments for advanced melanoma are associated with different adverse events (AEs), which may be costly to manage. This study aimed to evaluate direct costs associated with managing treatment-related AEs for advanced melanoma through a systematic literature review.<h4>Methods</h4>Systematic searches were conducted of the PubMed, Embase, Cochrane, BIOSIS, and EconLit medical literature databases to identify studies providing estimates of direct costs and health care resource u ...[more]

PMID: 30075584

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Project description:INTRODUCTION:Objective response rates (ORR) appear to be higher in melanoma patients who develop immune-related adverse events (irAEs), but whether there is a similar association between irAEs and survival remains unknown. MATERIALS AND METHODS:Patients with advanced melanoma treated with single-agent pembrolizumab or nivolumab in the province of Alberta from June 2014 to May 2017 were identified through the provincial pharmacy database. Chart review identified and categorized all irAEs that occurred while on anti-programmed cell death protein 1 (PD-1) checkpoint inhibitors. The primary objective was to compare overall survival (OS) with patients who developed any irAEs versus those who did not. Secondary outcomes included progression-free survival (PFS) and ORR. RESULTS:Among 186 patients, any-grade and grade ?3 irAEs occurred in 88 (47%) and 27 (15%) patients, respectively; one patient died of pneumonitis. In a landmark analysis excluding patients who died within the first 12?weeks, the median follow-up was 24 months, 20 months in patients without any irAEs and 26 months in patients with irAEs (p = .006). Median OS was 39 versus 23 months (hazard ratio [HR], 0.46; p = .001) for any irAE and no irAE, respectively, and median OS not reached versus 29 months for grade ?3 irAEs and no grade ?3 irAEs, respectively. In multivariate analysis, elevated lactate dehydrogenase correlated with reduced OS (HR, 2.34; p = .001), whereas each additional cycle of treatment received (HR, 0.94; p <?.001) and development of grade ?3 irAEs (HR, 0.29, p = .024) were significantly associated with longer OS. CONCLUSION:Anti-PD-1-associated grade ?3 irAEs in patients with advanced melanoma is associated with better patient outcomes, including overall survival. IMPLICATIONS FOR PRACTICE:Previous prospective randomized clinical trials demonstrate improved response rates in patients with melanoma who develop select adverse events. The current population-based real-world study in advanced melanoma reports an association with anti-programmed cell death protein 1 (PD-1)-induced grade ?3 immune-related adverse events (irAEs) and better patient outcomes, including overall survival. These results suggest that irAEs may be a manifestation of a patient's ability to mount a systemic immune response from PD-1-directed therapies, which may be associated with therapeutic benefit. The finding of irAEs coinciding with clinical benefit from these therapies supposes that these events are, by and large, unavoidable, and the critical management of irAEs remains essential for optimizing patient outcomes.

Project description:In Japan, medical costs are increasing annually, and the increase in national medical costs, particularly in the direct cost of managing adverse drug events, is high. An in-depth understanding of these costs is important for their reduction. This study aimed to calculate the direct cost of managing adverse drug events in all ages, including older adults, and that of avoidable adverse drug events in older adults. We conducted a retrospective survey on patients aged 1 year or older who visited Gifu Municipal Hospital in Japan. We investigated and calculated the direct cost of managing adverse drug events and that of avoidable adverse drug events based on the Beers Criteria Japanese version (BCJ) and "Guidelines for medical treatment and its safety in the elderly 2015" (GMTSE-2015) in inpatients and outpatients. Among 6,504 patients, 11.1% visited the hospital or were hospitalized due to adverse drug events. The direct costs per patient with adverse drug events were 21,281 and 22,590 yen (166 and 176 euros as on September 13, 2021) for outpatients, and 853,175 and 874,582 yen (6,648 and 6,815 euros) for inpatients of all ages and older adults, respectively. The direct costs of avoidable adverse drug events per patient using drugs listed in the BCJ and GMTSE-2015 for older adults were 3,212 and 3,341 yen (25 and 26 euros) for outpatients, and 55,548 and 80,246 yen (433 and 625 euros) for inpatients, respectively. In sum, considering both inpatients and outpatients in the whole country, the direct costs of managing adverse drug events were 804.53 billion and 597.19 billion yen (6,269 million and 4,653 million euros) per year for all ages and older ages, respectively. The direct cost of avoidable adverse drug events in older adults was 83.43-258.44 billion yen (650-2,013 million euros) per year. We found that, in Japan, high medical costs are often caused by managing adverse drug events, and that the costs of avoidable adverse drug events in older adults based on the BCJ and GMTSE-2015 account for a substantial proportion of the medical cost. Therefore, by using the BCJ and GMTSE-2015, avoiding adverse drug events and reducing medical costs may be possible.

Project description:ImportanceSince 2011, immune checkpoint inhibitors (ICIs) have been effective treatment options for advanced melanoma. Little is known about how risks of immune-related adverse events (irAEs) vary by ICIs.ObjectiveTo compare the risk of irAEs across different treatment regimens for advanced melanoma using network meta-analysis.Data sourcesPubMed/MEDLINE, Embase, Web of Science, and Scopus were searched for all randomized clinical trial (RCT) articles published from January 1, 2010, through June 30, 2019.Study selectionStudies included phases 2 and 3 RCTs in the treatment of advanced melanoma that compared ICIs (ipilimumab, nivolumab, and pembrolizumab) with chemotherapy drugs (eg, dacarbazine, carboplatin, and paclitaxel) or different ICI regimens.Data extraction and synthesisDifferent treatment regimens were compared using bayesian network meta-analysis with Markov chain Monte Carlo simulation with noninformative prior distribution and random-effects generalized linear models.Main outcomes and measuresPrimary outcomes were the cumulative incidence of any irAEs (regardless of severity) and severe irAEs (grades 3-5). Based on the pooled odds ratios (ORs) and 95% credible intervals (95% CrI), the probability of being associated with the lowest irAE risks was estimated for each treatment regimen.ResultsNine RCTs with 8 different treatment regimens for advanced melanoma and involving a total of 5051 patients were included. Overall, the 3 ICI treatment regimens associated with the lowest risk of any or severe irAEs were pembrolizumab, 2 mg/kg, every 3 weeks; nivolumab, 3 mg/kg, every 2 weeks; and pembrolizumab, 10 mg/kg, every 3 weeks. Compared with ipilimumab, 10 mg/kg, every 3 weeks, only nivolumab, 3 mg/kg, every 2 weeks, was associated with a decreased risk for any irAEs (OR, 0.34; 95% CrI, 0.13-0.94). A decreased risk for severe irAEs was observed for ipilimumab, 3 mg/kg, every 3 weeks (OR,?0.35; 95% CrI,?0.14-0.74); pembrolizumab, 10 mg/kg, every 2 weeks (OR,?0.22; 95% CrI,?0.05-0.95) and 10 mg/kg every 3 weeks (OR,?0.20; 95% CrI,?0.06-0.68); and nivolumab, 3 mg/kg, every 2 weeks (OR,?0.20; 95% CrI,?0.07-0.48) compared with ipilimumab, 10 mg/kg, every 3 weeks. An increased risk for severe irAEs was associated with nivolumab, 1 mg/kg, every 3 weeks combined with ipilimumab, 3 mg/kg, every 3 weeks compared with other ICI regimens (ORs ranging from?4.09 [95% CrI, 1.73-10.99] to 7.40 [95% CrI, 1.12-49.29]) except ipilimumab, 10 mg/kg, every 3 weeks.Conclusions and relevanceThese findings suggest that for patients with advanced melanoma at high risk of irAEs, pembrolizumab, 2 mg/kg, every 3 weeks, nivolumab, 3 mg/kg, every 2 weeks, and pembrolizumab, 10 mg/kg, every 3 weeks may be the preferred treatment regimens (with respect to irAE risks) among the ICI regimens reported, whereas ipilimumab, 10 mg/kg, every 3 weeks alone and nivolumab, 1 mg/kg, every 3 weeks combined with ipilimumab, 3 mg/kg, every 3 weeks should be used with caution. A network analysis may be valuable for clinical decision-making when evidence from head-to-head comparisons is lacking.

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Direct costs associated with adverse events of systemic therapies for advanced melanoma: Systematic literature review.

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Direct costs associated with adverse events of systemic therapies for advanced melanoma: Systematic literature review.

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