Medication adherence among patients with advanced prostate cancer using oral therapies.

Aims: In light of the extended overall survival and improved quality of life provided by advanced prostate cancer (PC) oral therapies, this study aimed to describe treatment adherence to advanced PC oral therapies and evaluate associated patient characteristics and subsequent healthcare resource utilization (HRU). Patients & methods: Patients with advanced PC initiating apalutamide, enzalutamide or abiraterone acetate were identified from administrative data (October 1, 2014-September 30, 2019). Adherence and persistence at six months postinitiation were used to evaluate patient factors and HRU. Results: Aged ≥75 years, Black race, chemotherapy use and higher pharmacy paid amounts were associated with poor adherence/persistence, which translated to higher HRU. Conclusions: Strategies to increase adherence and persistence may improve patient outcomes and associated HRU.

Lay abstract This study included 27,262 patients with advanced prostate cancer who started taking one of three oral cancer medications (apalutamide, enzalutamide or abiraterone acetate) between October 2014 and September 2019. Patients who were black, aged 75 years or older, who had chemotherapy or who had higher prescription costs had the most difficulty following dosing guidelines or staying on treatment. Patients who did not follow dosing guidelines required more healthcare services. In light of the extended survival and improved quality of life that oral cancer medication for advanced prostate cancer provides, helping patients to take the correct medication dose, at the right time, and for the recommended length of time may improve their outcomes and reduce medical costs.

Cost-effectiveness analysis of enzalutamide for patients with chemotherapy-naïve metastatic castration-resistant prostate cancer in Japan.

BACKGROUND: We aimed to evaluate cost-effectiveness of enzalutamide in chemotherapy-naïve metastatic castration-resistant prostate cancer patients in Japan. METHODS: A Markov model was developed to capture time spent by patients in various health states: stable, progression and death. Abiraterone acetate and docetaxel were set as active comparators. Clinical outcomes were obtained from the PREVAIL, COU-AA-302 and TAX327 trials. Treatment sequence, concomitant drugs and therapies for adverse events were estimated from responses to a survey by 14 Japanese prostate cancer experts. The analytic perspective was public healthcare payer, with a 10-year time horizon. The incremental cost-effectiveness ratio was estimated from quality-adjusted life-years and Japanese public healthcare costs. Probabilistic sensitivity analysis was performed to assess the robustness of the findings. RESULTS: According to the survey, the most common treatment sequences were (i) enzalutamide â†’ docetaxel â†’ cabazitaxel (enzalutamide-first sequencing), (ii) abiraterone â†’ enzalutamide â†’ docetaxel (abiraterone-first sequencing) and (iii) docetaxel→ enzalutamide â†’ cabazitaxel (docetaxel-first sequencing). In the base-case analysis, enzalutamide-first sequencing saved 1.74 million Japanese Yen versus abiraterone-first sequencing, with a 0.129 quality-adjusted life-year gain (dominant). Enzalutamide-first sequencing had a cost increase of 4.44 million Japanese Yen over docetaxel-first sequencing, with a 0.371 quality-adjusted life-years gain. The incremental cost-effectiveness ratio of enzalutamide-first sequencing versus docetaxel-first sequencing was estimated as 11.94 million Japanese Yen/quality-adjusted life-years. Probabilistic sensitivity analyses demonstrated that, compared with abiraterone-first sequencing, enzalutamide-first sequencing had an 87.4% probability of being dominant. CONCLUSIONS: Results modeled herein suggest that the enzalutamide-first sequencing is more cost-effective than the abiraterone-first sequencing, but less cost-effective than docetaxel-first sequencing for chemotherapy-naïve patients with metastatic castration-resistant prostate cancer.

Budget impact analysis of darolutamide for treatment of nonmetastatic castration-resistant prostate cancer.

BACKGROUND: Darolutamide, a structurally distinct androgen receptor inhibitor approved for the treatment of men with nonmetastatic castration-resistant prostate cancer (nmCRPC), has been shown to increase metastasis-free survival among men with nmCRPC compared with placebo. This treatment has a novel chemical structure that may also have safety, tolerability, and efficacy advantages for men with nmCRPC. OBJECTIVE: To estimate the projected budget impact of including darolutamide on a U.S. payer formulary as a treatment option for men with nmCRPC. METHODS: A budget impact model was developed to evaluate darolutamide for nmCRPC for a hypothetical 1-million-member plan over a 5-year period. Costs (drug acquisition, drug administration, and treatment-related adverse events [AEs]) were estimated for 2 scenarios: with and without darolutamide treatment for nmCRPC. The budget impact of darolutamide was calculated as the difference in costs for these 2 scenarios. An analysis for high-risk nmCRPC also was conducted. The model included treatments recommended by the National Comprehensive Cancer Network (e.g., apalutamide and enzalutamide) and potential comparators that are used but are not specifically indicated for nmCRPC. All treatments were assumed to be administered in combination with a weighted average androgen deprivation therapy comparator (consisting of luteinizing hormone-releasing hormone [LHRH] agonists, LHRH antagonists, and first-generation antiandrogens). Market share estimates were derived from interviews with physicians treating men with nmCRPC. The model includes grade 3-4 AEs, and the rates were obtained from clinical trial data. Costs were taken from publicly available sources and varied in a one-way sensitivity analysis. RESULTS: For a plan with 1 million lives, there were approximately 90 incident cases of nmCRPC (46 high risk) each year, with 332 (109 high risk) treatment-eligible cases by year 5. Darolutamide's market share increased from 3.6% in year 1 to 18% in year 5. Given the utilization of other agents, introducing darolutamide along with other targeted therapies was predicted to increase the total budget by $158,640 ($0.0132 per member per month [PMPM]) in year 1, which decreased over time to a cost savings of $149,240 ($0.0124 PMPM) by year 5. The scenario with darolutamide showed reduced AE costs each year. Similar results were observed for the high-risk nmCRPC population. CONCLUSIONS: Adding darolutamide to a U.S. payer formulary for the treatment of nmCRPC can result in a manageable increase in the budget that is partly offset by AE costs in the first 4 years, followed by a cost savings by year 5. DISCLOSURES: This study was conducted by RTI Health Solutions under the direction of Bayer U.S. and was funded by Bayer U.S., which was involved in the design of the study; collection, analysis, and interpretation of the data; writing of the report; and the decision to submit the report for publication. Miles and Purser (and/or their institutions) are employees of RTI Health Solutions and received research funding from Bayer U.S. to develop the budget impact model. Appukkuttan and Farej are employees of Bayer U.S. Wen was an employee of Bayer U.S. at the time of the study. This study was presented as a poster at the AMCP Virtual Learning Event, April 20-24, 2020.

Adherence and out-of-pocket costs among Medicare beneficiaries who are prescribed oral targeted therapies for advanced prostate cancer.

BACKGROUND: Abiraterone and enzalutamide are high-cost oral therapies that increasingly are used to treat patients with advanced prostate cancer; these agents carry the potential for significant financial consequences to patients. In the current study, the authors investigated coping and material measures of the financial hardship of these therapies among patients with Medicare Part D coverage. METHODS: The authors performed a retrospective cohort study on a 20% sample of Medicare Part D enrollees who underwent treatment with abiraterone or enzalutamide between July 2013 and June 2015. The authors described the variability in adherence rates and out-of-pocket payments among hospital referral regions in the first 6 months of therapy and determined whether adherence and out-of-pocket payments were associated with patient factors and the socioeconomic characteristics of where a patient was treated. RESULTS: There were 4153 patients who filled abiraterone or enzalutamide prescriptions through Medicare Part D in 228 hospital referral regions. The mean adherence rate was 75%. The median monthly out-of-pocket payment for abiraterone and enzalutamide was $706 (range, $0-$3505). After multilevel, multivariable adjustment for patient and regional factors, adherence was found to be lower in patients who were older (69% for patients aged ≥85 years vs 76% for patients aged <70 years; P < .01) and in those with low-income subsidies (69% in those with a subsidy vs 76% in those without a subsidy; P < .01). Both Hispanic ethnicity and living in a hospital referral region with a higher percentage of Hispanic beneficiaries were found to be independently associated with higher out-of-pocket payments for abiraterone and enzalutamide. CONCLUSIONS: There were substantial variations in the adherence rate and out-of-pocket payments among Medicare Part D beneficiaries who were prescribed abiraterone and enzalutamide. Sociodemographic patient and regional factors were found to be associated with both adherence and out-of-pocket payments.

Momelotinib for the treatment of myelofibrosis.

Introduction: The abnormally activated JAK-STAT pathway plays a central role in the pathogenesis of BCR/ABL-negative myeloproliferative neoplasms (MPNs), simultaneously providing a theoretical and clinical basis for the development of small-molecule compounds targeting JAK. The first approved drug, ruxolitinib, demonstrated a rapid and durable improvement of symptoms and splenomegaly accompanied with better overall survival in myelofibrosis (MF) patients. However, ruxolitinib-related adverse effects and resistance are limitations, so there is an urgent need to develop new JAK inhibitors to retain the efficacy of ruxolitinib and avoid its deficiency. Areas covered: This review discusses the preclinical and clinical studies of momelotinib (MMB) aiming to gain a deeper understanding of the advantages and clinical limitations of this drug. Expert opinion: The clinical trial data available thus far indicate that MMB is not inferior to ruxolitinib in spleen response and symptoms response, with the improvement of anemia surprising. The only obstacle that may slowdown its approval is treatment-emerged peripheral neuropathy (PN). If we can minimize MMB's treatment-related PN by administration optimization, MMB promises to be a good choice of individualized treatment for MF patients mainly manifesting as anemia.

Phase I/II Clinical Trial-Based Early Economic Evaluation of Acalabrutinib for Relapsed Chronic Lymphocytic Leukaemia.

OBJECTIVES: The objective of this study was to construct an early economic evaluation for acalabrutinib for relapsed chronic lymphocytic leukaemia (CLL) to assist early reimbursement decision making. Scenarios were assessed to find the relative impact of critical parameters on incremental costs and quality-adjusted life-years (QALYs). METHODS: A partitioned survival model was constructed comparing acalabrutinib and ibrutinib from a UK national health service perspective. This model included states for progression-free survival (PFS), post-progression survival (PPS) and death. PFS and overall survival (OS) were parametrically extrapolated from ibrutinib publications and a preliminary hazard ratio based on phase I/II data was applied for acalabrutinib. Deterministic and probabilistic sensitivity analyses were performed, and 1296 scenarios were assessed. RESULTS: The base-case incremental cost-effectiveness ratio (ICER) was £61,941/QALY, with 3.44 incremental QALYs and incremental costs of £213,339. Deterministic sensitivity analysis indicated that survival estimates, utilities and treatment costs of ibrutinib and acalabrutinib and resource use during PFS have the greatest influence on the ICER. Probabilistic results under different development scenarios indicated that greater efficacy of acalabrutinib would decrease the likelihood of cost effectiveness (from 63% at no effect to 2% at maximum efficacy). Scenario analyses showed that a reduction in PFS did not lead to great QALY differences (- 8 to - 14% incremental QALYs) although it did greatly affect costs (- 47 to - 122% incremental pounds). For OS, the opposite was true (- 89 to - 93% QALYs and - 7 to - 39% pounds). CONCLUSIONS: Acalabrutinib is not likely to be cost effective compared with ibrutinib under current development scenarios. The conflicting effects of OS, PFS, drug costs and utility during PFS show that determining the cost effectiveness of acalabrutinib without insight into all parameters complicates health technology assessment decision making. Early assessment of the cost effectiveness of new products can support development choices and reimbursement processes through effective early dialogues between stakeholders.

[Induction of hospital indebtedness due to medicine purchases under monopoly conditions: the case of imatinib mesylate]. / Indução de endividamento hospitalar na compra de medicamento em situação de monopólio: o caso do mesilato de imatinibe.

Medicine expenditures consume a large share of the health budget, so knowledge on the use of these funds is essential for decision-making in public health and improvement of pharmaceutical care. This study analyzed the indebtedness of a high-complexity university hospital due to increased spending on imatinib mesylate. The descriptive study was based on analysis of documents and records in the Hospital Information System (SIH) from 2002 to 2010. Starting with inclusion of the medicine in the budget, the study mapped strategies by the pharmaceutical industry and government, as well as government responses to reduce the product's price. The systematization and publication of information stored in files and electronic databases can help monitor the results of programs funded by the Brazilian Ministry of Health.

Changing the cost of care for chronic myeloid leukemia: the availability of generic imatinib in the USA and the EU.

Imatinib is an oral tyrosine kinase inhibitor and considered to be the most successful targeted anti-cancer agent yet developed given its substantial efficacy in treating chronic myeloid leukemia (CML) and other malignant diseases. In the USA and the European Union (EU), Novartis' composition of matter patent on imatinib will expire in 2016. The potential impact on health system spending levels for CML after generic imatinib becomes available is the subject of significant interest among stakeholders. The extent of the potential savings largely depends on whether and to what extent prices decline and use stays the same or even increases. These are also empirical questions since the likely spending implications following generic imatinib's availability are predicated on multiple factors: physicians' willingness to prescribe generic imatinib, molecule characteristics, and health system priorities. This article discusses each of these issues in turn. We then review their implications for the development of country-specific cost-effectiveness models to predict the implications for cost and quality of care from generic imatinib.

Comparative evaluation of patients newly initiating first-generation versus second-generation tyrosine kinase inhibitors for chronic myeloid leukemia and medication adherence, health services utilization, and healthcare costs.

BACKGROUND: Chronic myeloid leukemia (CML) treatment guidelines recommend first-line therapy with either first- or second-generation tyrosine kinase inhibitors (1GTKI, 2GTKI), but do not specify which generation should be used first. OBJECTIVE: To examine the association between initiation of 2GTKI versus 1GTKI and medication adherence, health services utilization, and healthcare costs. METHOD: This was a retrospective cohort study utilizing administrative claims data from a single health plan within the US of commercial and Medicare patients newly initiating 1GTKI or 2GTKI therapy for CML between June 2010 and December 2011. Multivariate logistic regression was used to investigate the association between TKI therapy and adherence, defined as proportion of days covered ≥0.85. Multivariate logistic regression and generalized linear models examined the association between TKI and health services utilization and direct healthcare costs (plan and patient paid) during the 12 month follow-up period. RESULTS: Among the 368 patients included, there was no difference in adherence between patients initiating a 2GTKI compared to a 1GTKI (odds ratio = 0.88, 95% confidence interval [CI] 0.55-1.40). Initiating a 2GTKI was associated with increased outpatient visits (incidence rate ratio [IRR] = 1.12, 95% CI 1.06-1.20); however, there were no statistically significant differences in emergency room visits or inpatient visits between the treatment groups. Total costs were 1.3 times higher for 2GTKI initiators versus 1GTKI initiators ($86,509 versus $66,443; p = 0.001), with a significant difference in TKI pharmacy costs. CONCLUSIONS: Although there were no differences in adherence, hospitalizations, or emergency room visits among patients initiating a second- versus first-generation TKI, total all-cause costs and outpatient visits were higher for 2GTKI initiators. With the impending release of generic imatinib, these comparative data will become germane in the selection of a first-line TKI therapy. Because this study used claims from a single health plan, it may not be generalizable to the general population.

Generics in chronic myeloid leukemia: current arguments for and against and the established evidence.

Tyrosine kinase inhibitors became the mainstay of management in patients with chronic myeloid leukemia. The substantially high treatment cost has unfortunately been a major issue. Recent market entry of the imatinib generics are expected to lower the price and increase the availability of the drug worldwide. However, concerns about their efficacy and safety seem to slacken the approval of the generics in many countries. In this editorial, we discuss the current evidence on imatinib generics based mainly on Turkish experience and other limited data available.

Cost-effectiveness of nilotinib, dasatinib and imatinib as first-line treatment for chronic myeloid leukemia in Colombia, 2012.

INTRODUCTION: New tyrosine kinase inhibitor treatments for chronic myeloid leukemia based on nilotinib, dasatinib and imatinib have improved patient quality of life and have turned chronic myeloid leukemia from a fatal disease into a chronic disease. OBJECTIVE: To evaluate the cost-effectiveness of nilotinib, 600 mg, and dasatinib, 100 mg, each compared to imatinib, 400 mg, as first-line therapy in chronic myeloid leukemia in Colombia from a third-party payer's perspective. MATERIALS AND METHODS: A cost-effectiveness analysis was performed using a Markov model to evaluate a hypothetical cohort of one hundred 55 year-old patients with newly diagnosed chronic myeloid leukemia in the chronic phase, and the time horizon for the baseline case was established as being until the end of life. Progression-free life-years saved were considered the primary outcome. Transition probabilities for major molecular response, disease progression to accelerated phase or blast crisis, and chronic myeloid leukemia related deaths were analyzed in the model for each arm. A 3% discount rate was applied to all costs and patient outcomes. Model robustness was evaluated using both univariate and multivariate Montecarlo sensitivity analysis. RESULTS: Nilotinib was higher in expected progression-free life-years saved (15.21 vs. 12.64 for imatinib), followed by dasatinib (14.91 vs. 14.54 for imatinib). Imatinib had lower total lifetime costs. The incremental cost-effectiveness ratio was US$ 33,120.36 in the nilotinib arm and US$ 514,939.08 in the dasatinib arm per progression-free life-years (PF-LYs) saved, each compared to imatinib. When analyzing nilotinib versus dasatinib indirectly, nilotinib was found to be dominant due to higher efficacy (2.25 PF-LYs) and lower costs (US$ 44,674) in the baseline case. The average estimated cost to manage disease progression per year was US$ 101,978.78, considered to be the threshold. CONCLUSION: In Colombia, using PF-LYs as the efficacy outcome, nilotinib is highly cost-effective when compared to imatinib and dominant vs. dasatinib in first-line therapy for CML in chronic phase.

Cost sharing and adherence to tyrosine kinase inhibitors for patients with chronic myeloid leukemia.

PURPOSE: The introduction of imatinib, a tyrosine kinase inhibitor (TKI), has greatly increased survival for patients with chronic myeloid leukemia (CML). Conversely, nonadherence to imatinib and other TKIs undoubtedly results in disease progression and treatment resistance. We examined trends in imatinib expenditures from 2002 to 2011 and assessed the association between copayment requirements for imatinib and TKI adherence. PATIENTS AND METHODS: We used MarketScan health plan claims from 2002 to 2011 to identify adults (age 18 to 64 years) with CML who initiated imatinib therapy between January 1, 2002, and June 30, 2011, and had insurance coverage for at least 3 months before through 6 months after initiation (N = 1,541). Primary outcomes were TKI discontinuation and nonadherence. The primary independent variable was out-of-pocket cost for a 30-day supply of imatinib. By using a propensity-score weighted sample, we estimated the risk of discontinuation and nonadherence for patients with higher (top quartile) versus lower copayments. RESULTS: Monthly copayments for imatinib averaged $108; median copayments were $30 (range, $0 to $4,792). Mean total monthly expenditures for imatinib nearly doubled between 2002 and 2011, from $2,798 to $4,892. Approximately 17% of patients with higher copayments and 10% with lower copayments discontinued TKIs during the first 180 days following initiation (adjusted risk ratio [aRR], 1.70; 95% CI, 1.30 to 2.22). Similarly, patients with higher copayments were 42% more likely to be nonadherent (aRR, 1.42; 95% CI, 1.19 to 1.69). CONCLUSION: Patients with higher copayments are more likely to discontinue or be nonadherent to TKIs. Given the importance of these therapies for patients with CML, our data suggest a critical need to reduce patient costs for these therapies.

Increasing access to care for chronic myeloid leukemia patients: assessment of a scaling-up program.

BACKGROUND: The Glivec International Patient Assistance Program (GIPAP) is designed to provide access to the cancer therapy Imatinib (Glivec⊠), which is indicated for the treatment of chronic myelogenous leukemia (CML) and gastrointestinal stromal tumors (GIST). OBJECTIVES: To identify factors those influence the quality of care and structural improvements. Design . Physicians (n=50), hospital administrators (n=10) and Ministry of Health officials (n=7) in 39 developing countries participated in qualitative interviews. The interviews focused on the impact of GIPAP on service delivery, patient tracking systems and cancer registries, health financing, and workforce. RESULTS: Service delivery, patient management, access to care, diagnostic capacity, and health workers' skills improved at participants' institutions following implementation of GIPAP. CONCLUSIONS: Positive institutional changes that improve care of CML/GIST patients arose from GIPAP. Some of these changes may strengthen institutions' capacity to treat other diseases as well. The GIPAP model could be deployed to improve access to care for patients with other chronic diseases.

[Impact of depressive disorders on adherence to oral anti-cancer treatment]. / Impact de la dépression sur l'adhésion aux traitements anticancéreux oraux.

The improper adherence to therapy is an emerging medical and economic issue in oncology which raised with the increasing use of oral anti-cancer treatment. Currently, the average rate of non-adherence to oral anti-cancer therapy is estimated at around 21%. In this study, we use the examples of the imatinib treatment against chronic lymphocytic leukemia and the tamoxifene treatment against breast cancer to assess the negative consequences of the non-adherence to therapy in terms of medical outcome and health care cost. One of the main causes of non-adherence to these oral cancer treatments is depression. Surprisingly, this aspect is still relatively unknown to oncologists, while depression has been taken into account for the treatment of other chronic diseases (e.g. diabetes…). We therefore propose that cancer patients should be screened for depression throughout their treatment to improve the adherence to therapy. Cancer patients should have the opportunity to explain their own perception of their disease and their treatment that are key parameters in the onset of depression. The recent use of oral therapy in cancer treatment should thus be accompanied by the establishment of a global management of cancer patient on a case-by-case basis.

Cost-effectiveness of 3-year vs 1-year adjuvant therapy with imatinib in patients with high risk of gastrointestinal stromal tumour recurrence in the Netherlands; a modelling study alongside the SSGXVIII/AIO trial.

BACKGROUND: Surgical resection of gastrointestinal stromal tumour (GIST) is rarely curative in patients at high risk of tumour recurrence and therefore 1 year of post-surgery adjuvant imatinib therapy has been recommended in this sub-group. Recently, adjuvant imatinib therapy administered for 3 years has been demonstrated to further increase recurrence-free survival and overall survival. The goal of this study was to assess the economic value of extending the duration of adjuvant imatinib therapy in high-risk patients in the Netherlands. METHODS: A multistate Markov model was developed to simulate how patients' clinical status after GIST excision evolves over time until death. The model structure encompassed four primary health states: free of recurrence, first GIST recurrence, second GIST recurrence, and death. Transition probabilities between the health states, data on medical care costs, and quality-of-life were obtained from published sources and from expert opinion. RESULTS: The expected number of life years (or quality-adjusted life years, QALYs) was higher in the 3-year group than in the 1-year group, 8.91 (6.55) and 7.04 (5.18) years, respectively. In the 3-year and 1-year group, the expected total costs amounted to €120,195 and €79,361, of which, €74,631 (62%) and €27,619 (35%) were adjuvant therapy drug costs, respectively. The difference in health benefits, that is 1.87 life years or 1.37 QALYs, and costs, €40,835, resulted in incremental cost-effectiveness ratios (ICER) of €21,865 per life year gained, and €29,872 per QALY gained. LIMITATIONS: A limitation of the study was inherently related to the uncertainty around the predictions of RFS. Scenario analyses were conducted to test the sensitivity of different RFS predictions on the results. CONCLUSIONS: Delayed recurrence due to treatment with longer-term adjuvant imatinib therapy represents a cost-effective treatment option with an ICER below the generally accepted threshold in the Netherlands.