Development and testing of an alternative responder definition for EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI).

OBJECTIVES: Dryness, fatigue and joint/muscle pain are typically assessed in Sjögren's trials using European Alliance of Associations for Rheumatology Sjögren's Syndrome Patient Reported Index (ESSPRI). A Patient Acceptable Symptom State of <5 and a Minimal Clinically Important Improvement (MCII)/responder definition (RD) of ≥1 point or 15% on ESSPRI have previously been defined. This study explored alternative RDs to better discriminate between active treatment and placebo in trials. METHODS: Anchor-based and distribution-based methods were used to derive RD thresholds in blinded phase IIb trial data (N=190) and confirm these in blinded data pooled from three early phase II trials (N=126). The populations consisted of individuals with moderate-to-severe systemic primary Sjögren's. Anchors were prioritised by ESSPRI correlations and used in similar conditions. Triangulated estimates were discussed with experts (N=3). The revised RD was compared with the original using unblinded data to assess placebo and treatment responder rates. RESULTS: Patients were predominantly female (>90%), white (90%), with mean age of 50 years. Receiver operating characteristic estimates supported an MCII threshold of 1.5-1.6 in the phase II data, whereas correlation-weighted mean change estimates supported a low/minimal symptom severity threshold of ≥2. A low/minimal symptom severity of ≤3 showed the greatest sensitivity/specificity balance. Analyses in the pooled data supported these thresholds (MCII: 1.5-2.1; low/minimal symptom severity: 2.7-3.7). Unblinded analyses confirmed the revised RD reduced placebo rates. CONCLUSIONS: Completing a trial with an improvement of ≥1.5 points compared with baseline and an ESSPRI score of ≤3 points is a relevant RD for moderate-to-severe systemic Sjögren's and reduces placebo rates.

Economic Burden Associated With Nasal Polyposis Recurrence Among Commercially Insured Patients in the United States.

OBJECTIVE: To compare health care resource utilization (HRU) and costs among commercially insured patients with nasal polyposis (NP) with and without recurrence after endoscopic sinus surgery (ESS). STUDY DESIGN: Retrospective matched cohort study. SETTING: Adults with initial ESS or an NP excision after a new NP diagnosis were identified in Optum's Clinformatics Data Mart Database (October 1, 2014-December 31, 2019). METHODS: The index date was the date of NP recurrence, identified with a claims-based algorithm for the recurrent cohort, or a random date for the nonrecurrent cohort. Patients in both cohorts were matched 1:1 on baseline characteristics (12 months preindex) via propensity scores and exact matching factors. Annual HRU and costs (2019 US$) were compared between the matched cohorts at 12 months postindex. RESULTS: NP recurrence was identified among 3343 of 16,693 patients with initial ESS; after matching, each cohort comprised 1574 patients (median age, 54 years; 40% female) with similar baseline health care costs (recurrent, $34,420; nonrecurrent, $33,737). At 12 months postindex, the recurrent cohort had higher HRU, including 36% and 51% more outpatient and emergency department visits, respectively (all P < .01). Mean health care costs were $9676 higher in the recurrent cohort ($24,039) relative to the nonrecurrent cohort ($14,363, P < .01). The mean cost difference between cohorts was driven by $8211 in additional outpatient costs, as well as $6062 in additional NP-related outpatient costs, in the recurrent cohort (all P < .01). CONCLUSION: NP recurrence is associated with a substantial economic burden, which appears to be driven by outpatient services.

Qualitative Research with Patients and Physicians to Assess Content Validity and Meaningful Change on ESSDAI and ESSPRI in Sjögren's.

INTRODUCTION: European Alliance of Associations for Rheumatology (EULAR) Sjögren's Syndrome Disease Activity Index (ESSDAI) is a clinician-reported outcome (ClinRO) instrument, assessing Sjögren's disease activity from the physician perspective. EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI) is a patient-reported outcome (PRO) instrument, assessing patient-defined Sjögren's symptom severity. Both instruments are commonly used as clinical trial endpoints and have been psychometrically validated. However, qualitative evidence supporting content validity and what constitutes a meaningful change is limited. Qualitative evidence supporting Physician/Patient Global Assessment of disease activity and symptom severity (PhGA/PaGA) items used within anchor-based analyses for ESSDAI/ESSPRI is also lacking. METHODS: Qualitative, semi-structured, telephone/video interviews were conducted with patients with Sjögren's (n = 12) and physicians who specialise in Sjögren's (n = 10). Interviews explored: appropriateness of ESSDAI domain weights and meaningful improvements on domain/total scores from the physician perspective, appropriateness of ESSPRI's 2-week recall period from the patient/physician perspective, patients' perspectives on meaningful improvements in ESSPRI total scores, and patients'/physicians' interpretation of PhGA/PaGA items. RESULTS: Most ESSDAI domain weights were considered clinically appropriate. Generally, a one-category improvement in domain-level scores and a 3-point improvement in total ESSDAI scores were considered clinically meaningful. Most patients/physicians considered ESSPRI's 2-week recall period appropriate, and patients considered a 1-to-2-point ESSPRI total score improvement meaningful. PhGA/PaGA items developed for use as ESSDAI/ESSPRI anchors were consistently interpreted. CONCLUSIONS: The findings support use of ESSDAI and ESSPRI as Sjögren's clinical trials endpoints, as well as in clinical practice and other research settings. Qualitative data exploring meaningful change supports existing minimal clinically important improvement (MCII) thresholds.

European Alliance of Associations for Rheumatology (EULAR) Sjögren's Syndrome Disease Activity Index (ESSDAI) is an assessment used by physicians to measure how active Sjögren's is in individuals with the condition. EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI) is a questionnaire completed by individuals with Sjögren's to assess the severity of their symptoms. It is important to show that ESSDAI and ESSPRI are considered appropriate by physicians and individuals with Sjögren's, respectively, and that ESSPRI is well understood by individuals with Sjögren's completing the questionnaire. Therefore, interviews were conducted with physicians who specialise in Sjögren's to explore the appropriateness of ESSDAI, the level of improvement on the assessment that would be important to individuals with Sjögren's, and the appropriateness of the ESSPRI recall period (i.e. whether it is acceptable to ask individuals to remember their symptoms over the past 2 weeks). Interviews were also conducted with individuals with Sjögren's to explore their understanding and relevance of ESSPRI (including the 2-week recall period) and the level of improvement on the questionnaire that would be important to them. Most physicians and patients considered ESSDAI and ESSPRI appropriate, supporting their use in a range of settings including Sjögren's clinical trials, clinical practice and other research settings. Most physicians reported that a 3-point improvement in ESSDAI total score would be meaningful to individuals with Sjögren's. Individuals with Sjögren's reported that a 1-to-2-point improvement in ESSPRI total score would be meaningful.

Content Validity of Sjögren's Syndrome Symptom Diary and Functional Assessment of Chronic Illness Therapy-Fatigue in Patients with Sjögren's.

INTRODUCTION: Sjögren's Syndrome Symptom Diary (SSSD) and Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) are patient-reported outcome (PRO) instruments assessing Sjögren's symptoms. Original SSSD items have demonstrated content validity, however qualitative evidence supporting the updated 'tiredness' item and two new supplementary items is lacking. Although well established and validated in other rheumatic diseases, there is no qualitative evidence supporting content validity of FACIT-F in Sjögren's. This study addressed these evidence gaps to support use of SSSD and FACIT-F as clinical trial endpoints, in clinical practice and in other research settings. METHODS: Qualitative, semi-structured telephone interviews were conducted with patients with Sjögren's (n = 12) and expert Sjögren's physicians (n = 10). Patient interviews explored content validity (e.g., understanding and relevance) of the new and updated SSSD items, perceptions of item and total score meaningful change on SSSD, and understanding and relevance of FACIT-F items. Physician interviews explored opinions on various SSSD scoring approaches. RESULTS: The new and updated SSSD items and FACIT-F demonstrated good content validity. Most patients considered a two-point improvement on most SSSD items meaningful, as well as a one- or two-point total score improvement. Most physicians reported tracking changes in patient responses to individual items as the most appropriate SSSD scoring approach. CONCLUSIONS: SSSD and FACIT-F are content valid in a Sjögren's population, meeting an important criterion to support their use as clinical trial endpoints, but also their use in clinical practice and other research settings. Qualitative data exploring meaningful change will be valuable in supporting psychometrically derived responder definitions.

Sjögren's Syndrome Symptom Diary (SSSD) and Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) are questionnaires completed by individuals with Sjögren's to assess the severity of their symptoms. It is important to show that these questionnaires are well understood and relevant to the individuals who complete them. Therefore, interviews were conducted with individuals with Sjögren's to explore their understanding and relevance of new and updated SSSD questions. Similarly, the interviews explored whether the FACIT-F questionnaire was well understood and relevant to individuals with Sjögren's, as this has not been explored before. Interviews were also conducted with expert Sjögren's physicians to explore the best approach to scoring SSSD (e.g., calculating a total score or looking at scores on individual items). The new and updated SSSD questions and the FACIT-F questionnaire were well understood and considered relevant by most individuals with Sjögren's. This suggests these questionnaires are appropriate for use in Sjögren's clinical trials, clinical practice, and other research settings. Most individuals with Sjögren's considered an improvement of two points on individual SSSD questions to be important, as well as a one- or two-point improvement in their total SSSD score. Most physicians agreed on the best approach to scoring SSSD.

Clinical and economic analysis of patients with acute myeloid leukemia by FLT3 status and midostaurin use at a Comprehensive Cancer Center.

INTRODUCTION: Identification of cytogenetic and molecular abnormalities has become vital for the appropriate treatment of acute myeloid leukemia (AML). One of the most common molecular alterations in AML is the constitutive activation by internal tandem duplication of FMS-like tyrosine kinase 3 (FLT3). METHODS: This observational, retrospective, cohort study at the Huntsman Cancer Institute (HCI) had two time periods: 1) a historical pre-midostaurin time period which consisted of the FLT3 mutated (FLT3m) and FLT3 wild type (FLT3wt) cohorts from January 1, 2007, to December 31, 2016, and 2) a post-midostaurin cohort which consisted of the FLT3 mutated midostaurin-user cohort (early mido) from May 01, 2017 to December 31, 2018. RESULTS: In total, 39 patients were included in the FLT3m cohort, 61 in the FLT3wt cohort, and seven in the early mido cohort. FLT3m patients spent fewer days in the hospital during the first consolidation regimen and received fewer consolidation cycles compared to FLT3wt patients. Overall survival (OS) was similar between FLT3m and FLT3wt patients. For patients without hematopoietic stem cell transplant, OS was significantly shorter for FLT3m patients compared to FLT3wt patients. Mean AML related inpatient charges and physician charges for FLT3m patients were significantly higher than FLT3wt patients. CONCLUSION: The FLT3 mutation is historically associated with a shorter time to transplant and increased total health care charges. More information is needed to evaluate the real-world treatment strategies for FLT3-mutated patients in the presence of FLT3 inhibitors and the impact of these treatment strategies on clinical and economic outcomes.

Budget Impact of Dabrafenib and Trametinib in Combination as Adjuvant Treatment of BRAF V600E/K Mutation-Positive Melanoma from a U.S. Commercial Payer Perspective.

BACKGROUND: Before the approval of dabrafenib and trametinib in combination, there were no approved therapies in the adjuvant setting that target the RAS/RAF/MEK/ERK pathway. OBJECTIVE: To evaluate the budget impact of dabrafenib and trametinib in combination for adjuvant treatment of patients with BRAF V600 mutation-positive resected Stage IIIA, IIIB, or IIIC melanoma from a U.S. commercial payer perspective using data from the COMBI-AD trial, as well as other sources. METHODS: The budget impact of dabrafenib and trametinib in combination for patients with BRAF V600E/K mutation-positive, resected Stage IIIA, IIIB, or IIIC melanoma was evaluated from the perspective of a hypothetical population of 1 million members with demographic characteristics consistent with those of a commercially insured U.S. insurance plan (i.e., adults aged less than 65 years) using an economic model developed in Microsoft Excel. The model compared melanoma-related health care costs over a 3-year projection period under 2 scenarios: (1) a reference scenario in which dabrafenib and trametinib are assumed to be unavailable for adjuvant therapy and (2) a new scenario in which the combination is assumed to be available. Treatments potentially displaced by dabrafenib and trametinib were assumed to include observation, high-dose interferon alpha-2b, ipilimumab, and nivolumab. Costs considered in the model include those of adjuvant therapies and treatment of locoregional and distant recurrences. The numbers of patients eligible for treatment with dabrafenib and trametinib were based on data from cancer registries, published sources, and assumptions. Treatment mixes under the reference and new scenarios were based on market research data, clinical expert opinion, and assumptions. Probabilities of recurrence and death were based on data from the COMBI-AD trial and an indirect treatment comparison. Medication costs were based on wholesale acquisition cost prices. Costs of distant recurrence were from a health insurance claims study. RESULTS: In a hypothetical population of 1 million commercially insured members, 48 patients were estimated to become eligible for treatment with dabrafenib and trametinib in combination over the 3-year projection period; in the new scenario, 10 patients were projected to receive such treatment. Cumulative costs of melanoma-related care were estimated to be $6.3 million in the reference scenario and $6.9 million in the new scenario. The budget impact of dabrafenib and trametinib in combination was an increase of $549 thousand overall and 1.5 cents per member per month. CONCLUSIONS: For a hypothetical U.S. commercial health plan of 1 million members, the budget impact of dabrafenib and trametinib in combination as adjuvant treatment for melanoma is likely to be relatively modest and within the range of published estimates for oncology therapies. These results may assist payers in making coverage decisions regarding the use of adjuvant dabrafenib and trametinib in melanoma. DISCLOSURES: Funding for this research was provided to Policy Analysis Inc. (PAI) by Novartis Pharmaceuticals. Stellato, Moynahan, and Delea are employed by PAI. Ndife, Koruth, Mishra, and Gunda are employed by Novartis. Ghate was employed by Novartis at the time of this study and is shareholder in Novartis, Provectus Biopharmaceuticals, and Mannkind Corporation. Gerbasi was employed by PAI at the time of this study and is currently an employee, and stockholder, of Sage Therapeutics. Delea reports grant funding from Merck and research funding from Amgen, Novartis, Sanofi, Seattle Genetics, Takeda, Jazz, EMD Serono, and 21st Century Oncology, unrelated to this work.

Cost-effectiveness of dabrafenib and trametinib in combination as adjuvant treatment of BRAF V600E/K mutation-positive melanoma from a US healthcare payer perspective.

Objective: The COMBI-AD trial demonstrated the efficacy and safety of dabrafenib and trametinib in combination vs placebo as adjuvant treatment of patients with BRAF V600E/K mutation-positive resected Stage IIIA (lymph node metastasis >1 mm), IIIB, or IIIC melanoma. This analysis evaluated the cost-effectiveness of dabrafenib and trametinib vs observation from a US healthcare payer perspective.Methods: This evaluation employed a non-homogeneous, semi-Markov, cohort model with health states for relapse-free survival (RFS), post-locoregional recurrence (LR), post-distant recurrence (DR) receiving first-line treatment, and post-DR receiving second-line treatment. A 50-year modeling time horizon was used. Transition probabilities were estimated based on individual patient data (IPD) from the COMBI-AD trial. Health-state utilities were estimated using EuroQol (EQ-5D) index values from COMBI-AD and published sources. Direct medical costs associated with treatment of melanoma were considered, including costs of BRAF mutation testing, medication and administration costs for adjuvant and metastatic treatments, costs of treating recurrence, and costs of adverse events. Costs and quality-adjusted life-years (QALYs) were discounted at 3.0% annually.Results: Compared with observation, adjuvant dabrafenib and trametinib was estimated to result in a gain of 2.15 QALYs at an incremental cost of $74,518. The incremental cost-effectiveness ratio (ICER) was estimated to be $34,689 per QALY. In deterministic sensitivity analyses, the ICER was sensitive to the cost of dabrafenib and trametinib and the distribution used for projecting RFS beyond the end of follow-up in the COMBI-AD trial. At a cost-effectiveness threshold of $100,000 per QALY, the probability that dabrafenib and trametinib is cost-effective was estimated to be 92%.Conclusions: Given generally-accepted cost-effectiveness threshold values in the US, dabrafenib plus trametinib is likely to be a cost-effective adjuvant therapy for patients with BRAF mutation positive melanoma. These results may be useful for policy-makers in their deliberations regarding reimbursement and access to this treatment.

Targeted agents or immuno-oncology therapies as first-line therapy for BRAF-mutated metastatic melanoma: a real-world study.

Aim: Targeted therapy (TT) and immuno-oncology (IO) drugs are approved for patients with BRAF mutant metastatic melanoma (MM). We compared real-world outcomes for first-line (1L) TT versus 1L IO to evaluate optimal sequencing. Materials & methods: Physicians-identified BRAF mutant MM patients initiating 1L TT or IO therapies and extracted treatment, disease and clinical outcomes including disease response which were compared between TT and IO and individual regimens. Results: 440 MM patients (TT = 283, IO = 157) were identified. A higher proportion of TT patients had liver metastases (46.3 vs 35.0%) and abnormal lactate dehydrogenase (61.1 vs 42.7%). IO-treated had a RECIST-determined response rate of 45.9 versus 60.1% for TT and time on treatment of 7.2 versus 11.4 months, respectively. There was no survival difference between cohorts. Conclusion: Despite higher risk patients, 1L TT resulted in higher response rate and longer treatment duration suggesting a preferred 1L sequence.

Patient preferences for treatment of metastatic melanoma.

AIM: To investigate patient preferences for clinical attributes of first-line metastatic melanoma treatments. MATERIALS & METHODS: A discrete-choice experiment and best-worst scaling exercise were used to assess relative preferences for treatment attributes. RESULTS: The 200 survey respondents had distinct preferences. Avoiding a 30% risk of colitis or hormone gland problems and avoiding severe fever were more important to respondents than avoiding a 20% risk of extreme sun sensitivity (p < 0.05). Patients preferred taking pills to receiving intravenous infusions in a clinic. When attributes were combined, approximately 85% of respondents preferred a risk profile similar to targeted therapy over a profile similar to immunotherapy, holding efficacy constant. CONCLUSION: Taking patient preferences into account can help patients get the full benefit from metastatic melanoma therapies.

Tyrosine kinase inhibitor therapy treatment and discontinuation in patients with chronic myeloid leukemia in chronic phase in the United States: a clinical practice perspective.

Tyrosine kinase inhibitor (TKI) therapy discontinuation practice in patients with chronic myeloid leukemia chronic phase (CML-CP) was assessed in real-world practice prior to the release of recommendations on discontinuation. Data were collected from US oncologists/hematologists (through web-based physician survey and patient chart review) on TKI therapy discontinuation practice including monitoring, adequate response for discontinuation, relapse, and symptoms following discontinuation. From the physician survey, 34% of oncologists/hematologists attempted discontinuation, with two-thirds doing so outside of a trial. From the chart review, TKI therapy was discontinued in 3.4% of patients after they achieved an adequate response with the intention to remain CML-therapy-free until disease relapse. Among these patients, 21% relapsed and 17% had symptoms following discontinuation. There was a lack of consensus on the definition of adequate response suggesting that discontinuation was attempted without clear guidelines and under suboptimal conditions underscoring the need for physician education regarding guidelines for TKI therapy discontinuation.

Cost Effectiveness of Midostaurin in the Treatment of Newly Diagnosed FLT3-Mutated Acute Myeloid Leukemia in the United States.

OBJECTIVES: The aim of this study was to assess the cost effectiveness of midostaurin + cytarabine + daunorubicin (midostaurin arm) versus placebo + cytarabine + daunorubicin (placebo arm) in the treatment of adult patients with newly diagnosed FLT3-mutated acute myeloid leukemia (AML) who are eligible for standard cytarabine + daunorubicin chemotherapy, from a US third-party payer perspective. METHODS: A lifetime partitioned survival model with four health states (active disease, complete remission [CR], relapse, and death) was constructed. Efficacy inputs (time to CR or death, time to relapse or death, and overall survival) were estimated using data from the RATIFY trial (NCT00651261). Costs (inflated to 2016 US dollars) included treatment, drug monitoring, stem cell transplantation (SCT), adverse events costs, and medical costs associated with health states. Incremental costs per quality-adjusted life-year (QALY) and life-year (LY) gained were estimated. Deterministic (DSA) and probabilistic sensitivity analyses (and PSA) were performed to assess model robustness. RESULTS: In the base case, patients in the midostaurin arm incurred higher total direct costs over a lifetime compared with the placebo arm ($4,043,470 vs. $3,959,741), resulting in an incremental cost of $83,729; however, the midostaurin arm had better effectiveness, with 1.59 more LYs and 1.37 more QALYs. These led to a base-case incremental cost-effectiveness ratio (ICER) of $52,596 per LY, or $61,167 per QALY. Results were robust in the DSA. In the PSA, the probability of the midostaurin arm being cost-effective compared with the placebo arm was 65.9%, at a willingness to pay of $150,000/QALY. CONCLUSIONS: This analysis suggests that midostaurin is a cost-effective treatment for adult patients with newly diagnosed FLT3-mutated AML, from a US third-party payer perspective.

Stage III melanoma incidence and impact of transitioning to the 8th AJCC staging system: a US population-based study.

AIM: To estimate incidence of stage III melanoma using the American Joint Committee on Cancer (AJCC) staging, 7th and 8th edition. PATIENTS & METHODS: The SEER US cancer registry was analyzed (2010-2014). AJCC7 stages were recorded in the data; AJCC8 stages were inferred. RESULTS: Of 106,195 melanoma patients, 7669 and 7342 had stage III melanoma by AJCC7 and AJCC8, respectively (95% overlap). Nearly 30% of patients with AJCC7 stage III melanoma were reclassified in a higher stage III group by AJCC8 versus 7% in lower stage group. Regardless of the AJCC edition, incidence of stage III melanoma has increased from 2010 to 2014 both overall and within each stage III group. CONCLUSION: Providing appropriate management to this growing population of high-risk patients is a priority.

Patterns of treatment and BRAF testing with immune checkpoint inhibitors and targeted therapy in patients with metastatic melanoma presumed to be BRAF positive.

Patients with BRAF V600 (BRAF) mutated metastatic melanoma are eligible for therapy with both immune checkpoint inhibitors and targeted therapies, making treatment choice a complex decision. The present study aimed to describe patterns of treatment with immunotherapy and targeted therapy and BRAF testing in patients with metastatic melanoma presumed to have BRAF mutations (BRAF+) in the years following the approval of the newer generation of immune checkpoint inhibitors and targeted therapies (2014-2016). Two large US commercial claims databases [Truven Health Analytics MarketScan and IQVIA Real-World Data Adjudicated Claims - USA (IQVIA RWD Adjudicated Claims - USA)] were used. Patients were presumed BRAF+ if they received at least 2 lines of therapy of which at least 1 included targeted therapy. Sequence of lines of therapy and regimens used in first (1L), second (2L), and third (3L), as well as timing of BRAF testing by sequence of therapy were described. In the Truven sample (n=162), targeted therapy was used by 66% in 1L and by 54% in 2L, and 62% had a BRAF test; in the IQVIA RWD Adjudicated Claims - USA sample (n=247), targeted therapy was used by 62% in 1L and by 50% in 2L, and 68% had a BRAF test. Among those with a claim for a BRAF test prior to 1L, over two-thirds were initiated on targeted therapy. These findings suggest that the rate of BRAF testing remained low in the years following the approval of BRAF-targeted regimens for metastatic disease. Given the recently approved adjuvant treatment options for stage III melanoma, improving the rates of BRAF testing becomes increasingly important.

Postsurgical treatment landscape and economic burden of locoregional and distant recurrence in patients with operable nonmetastatic melanoma.

Surgery is the mainstay treatment for operable nonmetastatic melanoma, but recurrences are common and limit patients' survival. This study aimed to describe real-world patterns of treatment and recurrence in patients with melanoma and to quantify healthcare resource utilization (HRU) and costs associated with episodes of locoregional/distant recurrences. Adults with nonmetastatic melanoma who underwent melanoma lymph node surgery were identified from the Truven Health MarketScan database (1 January 2008 to 31 July 2017). Locoregional and distant recurrence(s) were identified on the basis of postsurgery recurrence indicators (i.e. initiation of new melanoma pharmacotherapy, new radiotherapy, or new surgery; secondary malignancy diagnoses). Of 6400 eligible patients, 219 (3.4%) initiated adjuvant therapy within 3 months of surgery, mostly with interferon α-2b (n=206/219, 94.1%). A total of 1191/6400 (18.6%) patients developed recurrence(s) over a median follow-up of 23.1 months (102/6400, 1.6% distant recurrences). Among the 219 patients initiated on adjuvant therapy, 73 (33.3%) experienced recurrences (distant recurrences: 13/219, 5.9%). The mean total all-cause healthcare cost was $2645 per patient per month (PPPM) during locoregional recurrence episodes and $12 940 PPPM during distant recurrence episodes. In the year after recurrence, HRU was particularly higher in patients with distant recurrence versus recurrence-free matched controls: by 9.2 inpatient admissions, 54.4 inpatient days, 8.8 emergency department admissions, and 185.9 outpatient visits (per 100 person-months), whereas all-cause healthcare costs were higher by $14 953 PPPM. It remains to be determined whether the new generation of adjuvant therapies, such as immune checkpoint inhibitors and targeted agents, will increase the use of adjuvant therapies, and reduce the risk of recurrences and associated HRU/cost.

Burden of Infections Among Chronic Myeloid Leukemia Patients Receiving Dasatinib or Nilotinib: A Real-World Retrospective Healthcare Claims Study in the United States.

INTRODUCTION: Tyrosine kinase inhibitors (TKI) have been demonstrated to prolong survival in patients with chronic myeloid leukemia (CML). However, TKIs may be associated with an increased risk of infections. This study compared healthcare resource utilization (HRU) and costs among patients with CML receiving dasatinib or nilotinib, with a focus on infection-related economic outcomes. METHODS: Two large administrative databases were used to identify adult patients newly diagnosed with CML who initiated dasatinib or nilotinib as first- (1L) or second-line (2L) therapy and were classified into the following 1L (dasatinib 1L/nilotinib 1L cohorts) or 2L (dasatinib 2L/nilotinib 2L) cohorts based on the initiated 1L/2L TKI therapy. Infection-related HRU and healthcare costs were compared between cohorts, separately for 1L and 2L. RESULTS: Cohorts included 1156 patients in the dasatinib 1L and 677 patients in the nilotinib 1L cohorts, 322 patients in the dasatinib 2L, and 207 in the nilotinib 2L cohorts. In 1L and 2L, infection-related HRU was higher for dasatinib than nilotinib cohorts. Infection-related inpatient (IP) days constituted a larger proportion of all-cause IP days in the 1L/2L dasatinib than 1L/2L nilotinib cohorts (dasatinib 1L/2L: 53%/58%; nilotinib 1L/2L: 50%/46%). Compared to the nilotinib cohort, the dasatinib cohort had higher all-cause total costs per patient per year by US$17,901 in 1L and $28,625 in 2L. Of the total cost difference, infection-related were $6048 (34%) in 1L and $28,192 (99%) in 2L, largely driven by IP cost differences (1L/2L: 96%/98%). CONCLUSIONS: Dasatinib was associated with higher HRU and healthcare costs compared to nilotinib, particularly related to infections. FUNDING: Novartis Pharmaceutical Corporation.

Healthcare resource utilization in patients with metastatic melanoma receiving first-line therapy with dabrafenib + trametinib versus nivolumab or pembrolizumab monotherapy.

OBJECTIVE: To compare healthcare resource utilization (HRU) between patients with metastatic melanoma (MM) initiated on first-line (1L) combination therapy with the BRAF inhibitor dabrafenib and the MEK inhibitor trametinib (D + T; oral) and those initiated on 1 L monotherapy with the anti-PD1 monoclonal antibodies nivolumab or pembrolizumab (N/P; intravenous). METHODS: Patients with melanoma initiated on D + T or N/P from Q1/2014 to Q2/2016 (defined as 1 L treatment for MM) were identified in the Truven MarketScan database. Entropy balancing was used to reweight the N/P cohort in order to make it comparable to the D + T cohort with respect to the mean and variance of baseline covariates. HRU outcomes during 1 L therapy, reported per patient-year (PPY), were described and compared between the two cohorts post-weighting (i.e. independently of baseline covariates). RESULTS: Of the 445 patients included, 202 and 243 were initiated on D + T and N/P, respectively. After weighting, patients initiated on N/P had more outpatient visits for drug administration during 1 L therapy than those initiated on D + T (difference = 18.6 visits PPY [95% CI = 16.0-21.1]). Patients initiated on N/P also had more outpatient office visits for reasons other than drug administration (difference = 8.1 visits PPY [95% CI = 1.9-13.7]). No significant differences were observed for other HRU parameters (i.e. inpatient admissions, inpatient days, and emergency department visits during 1 L therapy). CONCLUSIONS: HRU during 1 L therapy was generally similar between patients initiated on D + T and N/P. Nonetheless, patients initiated on N/P had more outpatient visits, including more outpatient visits for reasons unrelated to drug administration.