Clinical Outcomes in Patients With Refractory Anemia With Excess Blasts (RAEB) Who Receive Hypomethylating Agents (HMAs).

BACKGROUND: We sought to understand the clinical effectiveness associated with use of hypomethylating agents (HMAs) azacitidine (AZA) and decitabine (DEC) for patients with refractory anemia with excess blasts (RAEB; an established proxy for higher-risk myelodysplastic syndromes/neoplasms) in contemporary and representative real-world settings. PATIENTS AND METHODS: We used the Surveillance, Epidemiology and End Results (SEER)-Medicare database, a linkage of cancer registry and Medicare claims data, to identify patients aged ≥ 66 years diagnosed with RAEB, between 2009 and 2017 in the United States, and who received AZA or DEC as first-line therapy. Outcomes measured were overall survival (OS), event-free survival (EFS), and incidence of progression-related acute myeloid leukemia (AML). RESULTS: Of 973 eligible patients, 738 (75.8%) received AZA and 235 (24.2%) received DEC; 6.4% received hematopoietic cell transplantation during follow-up. In the overall population, median OS was 13.9 months (95% confidence interval [CI]: 12.9-15.0), median EFS was 5.2 months (95% CI: 4.9-5.7), and 38.0% of patients progressed to AML. Incidences of AML progression and death were 25.6% and 29.9%, respectively, at Year 1, and 34.3% and 44.8%, respectively, at Year 2. There were no significant differences in clinical benefits between AZA and DEC. CONCLUSION: Median OS with both HMAs remained significantly shorter than in the AZA-001 clinical trial, highlighting how patient outcomes vary between clinical and real-world settings. Further research is required to understand why these disparities exist.

Venetoclax in Combination with Azacitidine for the Treatment of Newly Diagnosed Acute Myeloid Leukemia: A Canadian Cost-Utility Analysis.

Treatment for acute myeloid leukemia (AML) typically involves intensive chemotherapy (IC); however, there is an unmet need for approximately 50% of AML patients who are deemed unfit or ineligible for IC. The purpose of this study was to evaluate, from a Canadian perspective, the economic impact of venetoclax in combination with azacitidine (Ven+Aza) for the treatment of patients with newly diagnosed AML who are 75 years or older or who have comorbidities that preclude using IC. A lifetime partitioned survival model was developed to assess the cost-effectiveness of Ven+Aza compared with Aza. Health states included event-free survival, progressive/relapsed disease, and death. Efficacy parameters were based on the VIALE-A trial. Analyses were conducted from Ministry of Health (MoH) and societal perspectives. Over a lifetime horizon, Ven+Aza was associated with a gain of 1.65 quality-adjusted life years (QALYs) compared with Aza. From an MoH perspective, Ven+Aza and Aza were associated with total costs of $204,305 and $82,333, respectively, resulting in an incremental cost-utility ratio of $73,841/QALY. Results were similar from a societal perspective. This economic evaluation demonstrates that, in comparison with Aza, Ven+Aza is a cost-effective strategy for the treatment of patients with newly diagnosed AML who are deemed unfit for IC.

Costs per patient achieving remission with venetoclax-based combinations in newly diagnosed patients with acute myeloid leukemia ineligible for intensive induction chemotherapy.

BACKGROUND: Venetoclax, in combination with azacitidine, decitabine, or low-dose cytarabine (LDAC), received confirmatory approval in 2020 by the US Food and Drug Administration for the treatment of newly diagnosed acute myeloid leukemia (AML) in patients aged 75 years or older or who are ineligible for intensive induction chemotherapy. The economic value associated with response to venetoclax combinations compared with other treatments for this patient population has not been comprehensively evaluated. OBJECTIVE: To assess the cost per patient achieving remission with venetoclax combination therapies, compared with other therapies for newly diagnosed patients with AML who are ineligible for intensive induction chemotherapy, from a US third-party payer perspective. METHODS: The analysis used treatment effect estimates (ie, complete remission [CR] + CR with incomplete blood count recovery [CRi]) from a network meta-analysis and annual cost estimates from a prior budget impact model. The model considered the total cost of care including the costs of drug and administration, adverse events, hospitalization, disease monitoring, blood transfusions, and subsequent AML management when patients discontinued active treatment. Costs per patient achieving CR + CRi associated with venetoclax + azacitidine, venetoclax + LDAC, azacitidine, decitabine, LDAC, and best supportive care (ie, treatment given with the intent to maximize quality of life without specific antileukemic intent, such as blood transfusion products and antibiotics) were calculated as the annual total cost of care per patient divided by the CR + CRi rate. All costs were adjusted to 2020 US dollars. RESULTS: Venetoclax combination therapies were estimated to have substantially lower costs per patient achieving CR + CRi (venetoclax + azacitidine: $473,960; venetoclax + LDAC: $428,071) than alternative treatments. Azacitidine was estimated to have the the highest cost per patient achieving CR + CRi ($1,197,438), followed by best supportive care ($869,849), LDAC ($689,101), and decitabine ($594,074). A pair-wise matrix of the difference between therapies estimated that both venetoclax + azacitidine and venetoclax + LDAC were associated with significantly lower costs per patient achieving CR + CRi than azacitidine (by $723,477 and $769,367, respectively) and LDAC (by $215,141 and $261,030; all P < 0.05). CONCLUSIONS: From a US third-party payer perspective, venetoclax in combination with azacitidine or LDAC was estimated to be associated with a significantly lower cost per patient achieving CR + CRi than azacitidine or LDAC among newly diagnosed patients with AML ineligible for intensive chemotherapy. DISCLOSURES: This research was supported by AbbVie Inc. and Genentech. The sponsors helped design the study, interpret the data, and draft the manuscript. Drs Bui and Kapustyan are employees of and have equity ownership in AbbVie; Dr Choi was an employee of AbbVie during the study's conduct and has equity ownership. Ms Ma and Dr Montez are employees of and have equity ownership in Genentech. Drs Song and Chai, Ms Yin, and Dr Betts are employees of Analysis Group, Inc., which has received funding from AbbVie and Genentech for the conduct of this research. Dr LeBlanc reports personal fees for consulting or advisory boards from AbbVie, Agios/Servier, AstraZeneca, Amgen, Astellas, BlueNote, CareVive, BMS/Celgene, Daiichi-Sankyo, Flatiron, Genentech, GSK, Pfizer, and Seattle Genetics; royalties from UpToDate; speakers bureau fees from Agios/Servier, AbbVie, and BMS/Celgene; and grants and/or research contracts from the American Cancer Society, AstraZeneca, BMS, Jazz Pharmaceuticals, and Seattle Genetics.

Number needed to treat and associated incremental costs of treatment with enzalutamide versus abiraterone acetate plus prednisone in chemotherapy-naïve patients with metastatic castration-resistant prostate cancer.

OBJECTIVE: Enzalutamide (ENZA) and abiraterone acetate plus prednisone (AA) are approved second-generation hormone therapies for chemotherapy-naïve metastatic castration-resistant prostate cancer (mCRPC). This study compared ENZA with AA in chemotherapy-naïve mCRPC by calculating the number needed to treat (NNT) and associated incremental costs to achieve one additional chemotherapy-naïve patient with mCRPC free of radiographic progression, chemotherapy, or death over a 1-year time horizon. METHODS: Clinical outcomes were obtained from the PREVAIL and COU-AA-302 trials. Three outcomes were evaluated: radiographic progression-free survival, time to cytotoxic chemotherapy initiation, and overall survival at 1 year. NNT was calculated as the reciprocal of the outcome event rate difference for ENZA compared with AA. The incremental costs to achieve one additional outcome at 1 year were calculated as the difference in cost per treated patient multiplied by the NNT. Per-treated-patient costs were considered from a US payer perspective and included medications, monitoring, adverse events, post-progression treatments, and end-of-life care. RESULTS: Within a 1-year time horizon, the total cost per treated patient for ENZA was $2,666 less than AA. Compared with AA, treating 14 patients with ENZA resulted in one additional patient free of progression or death over 1 year; treating 26 patients with ENZA resulted in one additional patient with chemotherapy delayed over 1 year; and treating 91 patients with ENZA resulted in one additional patient free of death over 1 year. Therefore, ENZA is cost-effective compared with AA for all three outcomes evaluated, and the modeled results suggest ENZA is associated with potentially improved clinical outcomes in delaying chemotherapy initiation and disease progression for chemotherapy-naïve patients. The results are robust in sensitivity analyses, where the effect of changes in key model inputs and assumptions were tested. CONCLUSION: The results modeled in the present study suggest ENZA is cost-effective compared with AA for treating chemotherapy-naïve patients with mCRPC.

Budget Impact of Enzalutamide for Chemotherapy-Naïve Metastatic Castration-Resistant Prostate Cancer.

BACKGROUND: Prostate cancer is expected to account for approximately one quarter of all new diagnoses of cancer in American men in 2015. The cost of prostate cancer care is expected to reach $15.1 billion by the year 2020, up from $11.9 billion in 2010. Given the high burden of prostate cancer, health care payers are interested in quantifying the potential budget impact of new therapies. OBJECTIVE: To estimate the budget impact of enzalutamide for the treatment of chemotherapy-naïve metastatic castration-resistant prostate cancer (mCRPC) from a U.S. payer perspective. METHODS: A model was developed to assess the budget impact of enzalutamide for treatment of chemotherapy-naïve mCRPC patients in a hypothetical 1-million-member U.S. health plan over a 1-year time horizon. Comparators included abiraterone acetate, sipuleucel-T, radium Ra 223 dichloride, and docetaxel. Epidemiologic data, including National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) incidence rates, were used to estimate the number of chemotherapy-naïve mCRPC patients. Dosing, administration, duration of therapy, and adverse event rates were based on package inserts and pivotal studies. Drug costs were obtained from RED BOOK and Centers for Medicare & Medicaid Services (CMS) average sales price pricing files, costs of administration and monitoring from the CMS physician fee schedule, and adverse events from the Agency for Healthcare Research and Quality Healthcare Cost and Utilization Project and published literature. Market shares were estimated for each comparator before and after adoption of enzalutamide. The incremental aggregate budget impact, per patient per year (PPPY), per patient per month (PPPM), and per member per month (PMPM), was calculated. One-way sensitivity analyses were performed. RESULTS: In a population of 115 chemotherapy-naïve mCRPC patients, adopting enzalutamide had an annual incremental budget impact of $510,641 ($4,426 PPPY, $369 PPPM, and $0.04 PMPM). Results were most sensitive to enzalutamide drug cost, size of the chemotherapy-naïve mCRPC patient population, and enzalutamide adoption rate. CONCLUSIONS: Results indicate a modest 1-year budget impact of adopting enzalutamide for chemotherapy-naïve mCRPC patients, partly because of the cost offset of a moderate incidence of adverse events and lack of additional required monitoring.

Resource utilization and use of life-extending therapies and corticosteroids in prostate cancer patients with corticosteroid-sensitive comorbidities.

OBJECTIVES: Corticosteroids (CSs) are used concomitantly with life-extending therapies (LETs) in patients with castration-resistant prostate cancer (CRPC). This study examined time to LETs, LETs and concomitant CS adherence, and monthly all-cause healthcare utilization and costs in patients with CPRC with and without CS-sensitive comorbidities in the Veterans Health Administration population. METHODS: Patients had CRPC if records showed prostate cancer diagnosis, medical/surgical castration and ≥2 prostate-specific antigen increases through 1 June 2007-31 May 2012. CS-sensitive comorbidities were assessed 6 months prior to the index date. Adherence, defined as medication possession ratio (MPR) ≥0.8, among patients initiating LETs (cabazitaxel, docetaxel, or abiraterone acetate) before 30 November 2011, resource utilization and costs among patients with concomitant CS were assessed. Statistical analysis included descriptive, Cox proportional hazards, and logistic regression models. RESULTS: Common CS-sensitive conditions among 12,128 patients with CRPC included hypertension (75.74%) and hyperlipidemia (54.69%). Those with glaucoma (hazard ratio [HR] = 0.67), ischemic heart disease (HR = 0.78), and peripheral vascular disease (PVD) (HR = 0.78) were less likely to be prescribed LETs (all p < 0.01). Duration of LET was shorter among patients with CS-sensitive comorbidities (125.02 vs 133.08 days; p = 0.04) in the 6 month follow-up period. Among LET-treated patients with and without CS-sensitive comorbidities, less than half had MPR ≥ 0.8 (LET: 48.72% vs 54.05%; concomitant CS: 42.19% vs 40.54%, respectively). Cerebrovascular disease (odds ratio = 0.107; 95% confidence interval = 0.012 to 0.966) and PVD (odds ratio = 0.523; 95% confidence interval = 0.276 to 0.991) were associated with reduced CS adherence. Among patients with concomitant CS, those with CS-sensitive comorbidities had more inpatient stays than those without (20.45% vs 12.88%; p = 0.033), incurring higher monthly inpatient costs ($1157 vs $342; p < 0.0001) and total costs ($5725 vs $4772; p = 0.036). CONCLUSION: CS-sensitive conditions influence initiation and duration of LETs, concomitant CS adherence, inpatient stays, and total costs. Future efforts should focus on specific strategies for treating prostate cancer patients with CS-sensitive comorbidities to ensure that they have appropriate access to LETs and to reduce costs and inpatient stays. Study limitations include the use of retrospective claims data and the relatively restricted subpopulation of older North American males.

Cost-effectiveness analysis of anti-muscarinic agents for the treatment of overactive bladder.

OBJECTIVE: To determine the cost-effectiveness of pharmacologic treatments for overactive bladder (OAB) in the US. METHODS: A decision model was constructed based on studies of effectiveness, adverse consequences, co-morbid conditions, and medical costs for the treatment of OAB. Treatment success was defined as no incontinence episodes for 3-7 days or 3-7 consecutive dry days. Estimates of treatment success were obtained from clinical trials and included darifenacin, fesoterodine, oxybutynin immediate release (IR), oxybutynin extended release (ER), oxybutynin topical gel, oxybutynin transdermal patch, solifenacin, tolterodine IR, tolterodine ER, trospium IR, and trospium ER. Probabilistic sensitivity analysis was conducted using Monte Carlo simulation. RESULTS: A total of 51 OAB studies were identified and 11 reported treatment success. Mean continence rates varied in the literature from 21.0% with trospium IR to 51.0% with solifenacin. The 95% CI for solifenacin's success rate was statistically higher than other regimens due to the higher continence rates from the clinical trials. Oxybutynin IR and oxybutynin ER were significantly less costly than other products. The product with the lowest incremental cost-effectiveness ratio (ICER) relative to oxybutynin IR was solifenacin at $1338 (± 168) per additional continent patient. The cost-effectiveness acceptability curve indicated that oxybutynin IR was the most cost-effective regimen when willingness-to-pay values were less than $10,000 per additional continent patient. Solifenacin was most cost-effective at higher willingness-to-pay values. CONCLUSION: There was broad overlap in effectiveness among the anti-muscarinic products, except solifenacin had a significantly higher continence rate. Oxybutynin IR and oxybutynin ER were significantly less costly than other anti-muscarinic regimens, and these two products have a useful role to play in the management of OAB. However, for patients unable to tolerate the lower cost products, formularies benefit from solifenacin among branded products since the cost-effectiveness acceptability curve demonstrated it was the product most likely to be cost-effective after oxybutynin IR.

The Sequoyah corporation fuels release and the Church Rock spill: unpublicized nuclear releases in American Indian communities.

The Three Mile Island nuclear release exemplifies why there is public and policy interest in the high-technology, highly visible end of the nuclear cycle. The environmental and health consequences of the early steps in the cycle--mining, milling, and processing of uranium ore--may be less appreciated. We examined 2 large unintended acute releases of uranium--at Kerr McGee's Sequoyah Fuels Corporation in Oklahoma and United Nuclear Corporation's Church Rock uranium mill in New Mexico, which were incidents with comparable magnitude to the Three Mile Island release. We urge exploration of whether there is limited national interest and concern for the primarily rural, low-income, and American Indian communities affected by these releases. More attention should be given to the early stages of the nuclear cycle and their impacts on health and the environment.