A real-world, retrospective, observational study examining treatment patterns and clinical outcomes in patients with FLT3m + AML in Japan.

OBJECTIVE: Acute myeloid leukemia (AML) is the most common form of leukemia among adults in Japan. This study aimed to understand the treatment patterns, health care resource utilization, and costs of FMS-like tyrosine kinase 3 mutation-positive (FLT3m+) AML patients in Japan. METHODS: A retrospective cohort study of Japanese FLT3m + AML patients was conducted using data extracted from a national hospital-based claims database provided by Medical Data Vision Co. Ltd. (MDV; Tokyo, Japan). Patients were identified from the MDV database between April 2008 and April 2021 inclusive. RESULTS: A total of 360 patients were included in this study. The study results suggest that cytarabine + anthracyclines was the most common first-line (1 L) treatment, accounting for 41.3% of the patients. FLT3 inhibitors (FLT3i) was the most common treatment across the study period (95.7%). The mean age of patients was 62.4 years, and most were 65 years or older. The median overall survival (OS) after initiating FLT3i treatment was 394 days. The median treatment duration of FLT3i was 88.5 days, while it was 66.0 days for patients treated with FLT3i within 60 days after hematopoietic stem cell transplantation (HSCT). The overall mean monthly total treatment cost was JPY 2,009,531.7/per patient per month (PPPM) (USD 17,967.9/PPPM). CONCLUSIONS: The study found specific treatment patterns, trends and features in patients with FLT3m + AML. FLT3i was the most prescribed treatment across the study period and the overall median OS after initiating FLT3i treatment was over 1 year. The findings of this study could be helpful for clinicians to optimize treatment strategies for FLT3m + AML in Japan.

A multicenter, retrospective observational study investigating baseline characteristics and clinical outcomes in patients with hormone-sensitive prostate cancer treated with primary androgen deprivation therapy.

OBJECTIVE: This multicenter, retrospective, observational study investigated baseline characteristics and clinical outcomes in patients with hormone-sensitive prostate cancer who received primary androgen deprivation therapy, using Japan Study Group of Prostate Cancer registry data. METHODS: Among patients in the Japan Study Group of Prostate Cancer registry, those who initiated primary androgen deprivation therapy and were aged 20 years or older were enrolled in this study. The primary endpoint was time to disease progression, defined as time from primary androgen deprivation therapy initiation to either prostate-specific antigen or clinical progression. Secondary endpoints included prostate-specific antigen progression-free survival, prostate-specific antigen response (90% or greater reduction from baseline) and distribution of second-line treatment. RESULTS: Of the 2494 patients (goserelin, n = 564; leuprorelin, n = 1148; surgical castration, n = 161; degarelix, n = 621), those who received degarelix had higher prostate-specific antigen levels and Gleason scores and were at a more advanced clinical stage than those receiving goserelin or leuprorelin. The median time to disease progression (identical to the prostate-specific antigen progression-free survival result) was not reached for goserelin and leuprorelin, 52.7 months for surgical castration and 54.0 months for degarelix. Although baseline prostate-specific antigen values in the degarelix cohort were higher than those of the leuprorelin or goserelin cohorts, prostate-specific antigen responses were not different among the three cohorts. Regarding second-line treatment, the largest patient group received degarelix followed by leuprorelin (n = 195). CONCLUSIONS: This study clarified patient characteristics and long-term effectiveness of primary androgen deprivation therapy in real-world clinical practice. Japanese urologists appear to select appropriate primary androgen deprivation therapy based on patient background and tumour characteristics, with degarelix largely reserved for higher risk patients.

[Cost-Effectiveness Analysis and Budget Impact Analysis of Enzalutamide for the Treatment of Metastatic Hormone-Sensitive Prostate Cancer].

We conducted cost-effectiveness analysis and budget impact analysis for androgen deprivation therapy (ADT) plus enzalutamide (ENZ) on patients with metastatic hormone-sensitive prostate cancer (mHSPC) from the publicly-funded healthcare system perspective. Using a partitioned survival model, lifetime costs, quality-adjusted life years (QALYs) and incremental cost-effectiveness ratios (ICERs) of ADT＋ENZ were estimated against ADT alone, ADT plus abiraterone (ADT＋ABI), and ADT plus apalutamide (ADT＋APA). Total healthcare cost differences with and without ENZ in mHSPC therapy were estimated for the period from 2022 to 2026. Based on cost-effectiveness analysis, the ICER of ADT＋ENZ versus ADT alone was estimated as ￥7.18 million/QALY gained. ADT＋ABI and ADT＋APA were dominated options (extended dominance). Budget impact analysis showed that incorporation of ENZ had a net budget impact of ￥57.19 billion, an 8.4% increase, over these 5 years. This amounted to a budgetary impact of ￥16,000 per patient per month at year 5. However, the number of patients with disease progressed to metastatic castration-resistant prostate cancer (mCRPC) would be reduced from 79,000 (without ENZ) to 65,000 (with ENZ), resulting in a 17% cost reduction within the mCRPC phase. In conclusion, ADT＋ENZ would be a cost-effective option, at the willingness to pay threshold of ￥7.5 million/QALY gained. Introduction of ENZ in the mHSPC treatment would result in a marginal increase in the total budget. However, ENZ is also expected to provide clinical benefits in reducing the number of patients with disease that would otherwise progress to mCRPC during these 5 years, resulting in cost savings in this phase.

Interim results from a postmarketing surveillance study of patients with FLT3-mutated relapsed/refractory AML treated with the FLT3 inhibitor gilteritinib in Japan.

OBJECTIVE: Gilteritinib received approval for the treatment of FLT3-mutated relapsed or refractory acute myeloid leukemia in Japan in 2018. In accordance with regulatory requirements, we conducted a multicenter, observational surveillance of gilteritinib use in Japan. METHODS: Patients were followed for 6 months from gilteritinib treatment initiation. The primary endpoint of the surveillance was incidence of adverse drug reactions related to each element of the safety specification defined in the Japanese Risk Management Plan. This interim analysis presents data collected from 3 December 2018 to 20 September 2020. RESULTS: Among 204 patients with case report forms, 107 consented to data publication. Of these 107 patients, 59.8% (n = 64) were male and 58.9% (n = 63) were aged ≥65 years; most received a 120-mg/day initial (80.4%; 86/107) and maximum (74.8%; 80/107) daily dose. The discontinuation rate was 61.7% (66/107); the most common reasons for discontinuation were disease progression (18.7%), transplantation (16.8%) and adverse events (15.0%). The adverse drug reaction rate was 77.6%. The incidences of adverse drug reactions (grade ≥ 3) related to each element of the safety specification were myelosuppression, 44.9% (38.3%); liver function disorder, 24.3% (6.5%); infections, 24.3% (21.5%); prolonged QT interval, 10.3% (2.8%); hemorrhage, 9.3% (6.5%); renal dysfunction, 6.5% (0); hypersensitivity, 5.6% (1.9%); interstitial lung disease, 4.7% (3.7%); cardiac failure/pericarditis/pericardial effusion, 1.9% (0.9%); pancreatitis, 0.9% (0); posterior reversible encephalopathy syndrome, 0.9% (0.9%). The composite complete remission rate was 62.7%; the 6-month overall survival rate was 77.7%. CONCLUSION: Gilteritinib treatment for 6 months in Japan was associated with acceptable efficacy and no new safety concerns were observed.