Treatment patterns and cost estimations of systemic chemotherapy for pancreatic cancer in Japan: A retrospective database study.

BACKGROUND: This study aimed to clarify the treatment patterns of pancreatic cancer patients receiving systemic chemotherapy in Japan and to estimate the direct medical costs in actual practice. RESEARCH DESIGN AND METHODS: This retrospective cohort study used electronic health record data between April 2008 and December 2018 in Japan. Participants had a confirmed pancreatic cancer diagnosis and received at least one systemic chemotherapy, including FOLFIRINOX, gemcitabine plus nab-paclitaxel, gemcitabine, and S-1. The outcomes were treatment patterns and monthly medical costs and the distribution of monthly medical costs across healthcare resource categories. RESULTS: Of the 4514 selected patients, 40.7%, 7.1%, 24.4%, and 21.3% used gemcitabine plus nab-paclitaxel, FOLFIRINOX, gemcitabine, and S-1 as first-line chemotherapy, respectively. The median monthly medical costs were the highest in the first month, with gemcitabine plus nab-paclitaxel ranking first (6813 USD), followed by FOLFIRINOX, gemcitabine, and S-1. The health resource categories with the highest shares of monthly medical costs during the first-line treatment period with gemcitabine plus nab-paclitaxel and FOLFIRINOX were hospitalization costs (FOLFIRINOX: 41%-37%; gemcitabine plus nab-paclitaxel: 40%-34%) and medicine costs (FOLFIRINOX: 51%-42%; gemcitabine plus nab-paclitaxel: 49%-38%). CONCLUSIONS: This study sheds light on the current treatment patterns and direct medical costs of systemic chemotherapy for pancreatic cancer in Japan.

Health state utility values for metastatic pancreatic cancer using a composite time trade-off based on the vignette-based approach in Japan.

BACKGROUNDS: Limited information is available on the utility values of metastatic pancreatic cancer, focusing on different health statuses, selected chemotherapy, and related grades 1/2 and 3/4 adverse events (AEs). We evaluated Japanese societal-based health-related utility values for metastatic pancreatic cancer by considering different grade toxicities commonly associated with chemotherapy using the vignette-based method. METHODS: We developed health status scenarios for patients with metastatic pancreatic cancer undergoing chemotherapy and conducted utility research using the developed scenarios in four steps: 'literature review,' 'exploratory interview,' 'content validation', and 'utility research'. In the development process, to consider the impact of AEs of chemotherapy for metastatic pancreatic cancer on health state utility values, we selected neutropenia, febrile neutropenia, diarrhea, nausea and vomiting, and neuropathy as representative AEs. Each AE was classified as either grade 1/2 or 3/4. We confirmed our created scenarios through cognitive interviews with the general population and clinical experts to validate the content. Finally, we developed 11 scenarios for using 'utility research,' evaluated in a societal-based valuation study using the face-to-face method. Participants for 'utility research' were the general population, and they evaluated these scenarios in the composite time trade-off (cTTO) and visual analog scale (VAS) of the European quality of life (EuroQol) valuation technology to derive health state utility scores. RESULTS: Of 220 responders who completed this survey, 201 were adapted into the analysis population. Stable disease with no AEs (reference state) had a mean utility value of 0.653 using cTTO. The lowest mean utility score in the stable state was 0.242 (stable disease + grade 3/4 vomiting). VAS results ranged from 0.189 to 0.468, depending on the various grades of AEs in stable disease. In addition, grade 3/4 AEs and grade 1/2 nausea/vomiting were associated with significantly greater disutility. Utility values were also strongly influenced by the direct impact of AE on physical symptoms, severity and their experience. In addition, 95.9% of the respondents agreed that they understood the questions in the post-response questionnaire. CONCLUSIONS: We clarified the health state utility values of patients with metastatic pancreatic cancer based on the general population in Japan. The effect on utilities should be considered not only for serious AEs, but also for minor AEs.

Cost-Effectiveness of Trastuzumab With or Without Chemotherapy as Adjuvant Therapy in HER2-Positive Elderly Breast Cancer Patients: A Randomized, Open-Label Clinical Trial, the RESPECT Trial.

BACKGROUND AND OBJECTIVE: Trastuzumab is a standard care as adjuvant chemotherapy (AdjCT) for patients with human epidermal growth factor receptor 2 (HER2)-positive primary breast cancer (BC) in Japan. However, no reports have evaluated its economics for patients with HER2-positive BC over 70 years of age. The objective of this study was to evaluate the cost-effectiveness of HER2-targeted trastuzumab + chemotherapy in Japan, comparing it with trastuzumab monotherapy. METHODS: A three-state-partitioned survival model was developed to evaluate the cost-effectiveness of trastuzumab + chemotherapy versus trastuzumab monotherapy for AdjCT in elderly patients with HER2-positive BC. We derived the efficacy data, utilities, and costs of both arms from individual patient data in the RESPECT trial (NCT01104935) and published studies. The costs and quality-adjusted life years (QALYs) were discounted at 2% per annum using a payer perspective. The respective cost estimates were reported in 2019 Japanese Yen (JPY) or US dollars (US$). The primary outcome was the incremental cost-effectiveness ratio (ICER). We assured robustness with deterministic and probabilistic sensitivity analyses. RESULTS: The cost per patient for trastuzumab + chemotherapy was JPY 14.6 million (US$137,000), and their QALYs were 9.308, compared with JPY 14.2 million (US$131,000) and 9.101, respectively, for trastuzumab monotherapy. The ICER of trastuzumab + chemotherapy versus trastuzumab monotherapy was JPY 2.7 milllion/QALY (US$17,200/QALY). The ICER for trastuzumab with chemotherapy varied from "Dominant" to "Dominated" in one-way sensitivity analysis. CONCLUSIONS: The base-case analysis suggests that AdjCT with trastuzumab + chemotherapy is likely to be a cost-effective choice for patients with HER2-positive BC aged 70 years or older. However, the sensitivity analysis suggested uncertainty regarding the cost-effectiveness of trastuzumab + chemotherapy.

Comparative Outcomes of First-Line Chemotherapy for Metastatic Pancreatic Cancer Among the Regimens Used in Japan: A Systematic Review and Network Meta-analysis.

Importance: Various first-line chemotherapy treatment regimens for patients with metastatic pancreatic cancer have been approved in Japan, including gemcitabine (GEM); fluorouracil, leucovorin, irinotecan, and oxaliplatin combination (FOLFIRINOX); GEM plus albumin-bound paclitaxel (GEM+NPTX), and S-1 (tegafur + gimeracil + oteracil). However, direct comparisons of these chemotherapy regimens are limited. Objective: To assess the short-term and long-term outcomes associated with first-line chemotherapy regimens for metastatic pancreatic cancer compared with chemotherapy regimens recommended in Japanese guidelines. Data Sources: In this systematic review and network meta-analysis, the bibliographic databases PubMed, Cochrane Library, and Web of Science, as well as medical journals published between January 1, 2002, and December 31, 2018, were searched for clinical trials comparing chemotherapy regimens. Study Selection: Randomized 2-arm clinical trials evaluating first-line chemotherapy for advanced or metastatic pancreatic cancer were included. Data Extraction and Synthesis: The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) Extension Statement for Reporting of Systematic Reviews Incorporating Network Meta-analyses of Health Care Interventions was followed for data abstractions. Data were pooled using a random-effects model. The SIGN 50 Quality Assessment Instrument was used to assess the risk of bias and overall study quality of the selected trials. Main Outcomes and Measures: The primary end point was overall survival (OS), and the secondary end point was progression-free survival (PFS) compared with GEM for first-line chemotherapy for metastatic pancreatic cancer. The Kaplan-Meier curve of GEM from the literature and the estimated hazard ratios (HRs) were used to model the long-term associations to calculate the area under the curve (AUC) (person-months) for OS and PFS of each chemotherapy. Sensitivity analyses with multiple functional models were conducted to confirm the long-term estimations. Results: A total of 22 regimens (25 studies) for OS and a total of 18 regimens (21 studies) for PFS were identified from literature. The total number of participants was 10 186, with 5856 male (57.5%) and 4330 female (42.5%). The FOLFIRINOX and GEM+NPTX regimens were associated with reduction in the risk of death, with an HR of 0.57 (95% CI, 0.41-0.79) and 0.72 (95% CI, 0.55-0.95) compared with GEM, respectively. The curve estimation also showed that FOLFIRINOX had the largest AUC for survival at 15.49 person-months (range, 13.84-15.51 person-months), followed by GEM+NPTX with 12.36 person-months (range, 10.98-12.59 person-months), GEM+ERLO with 10.84 person-months (range, 9.66-11.23 person-months), S-1 with 8.44 person-months (range, 8.26-9.74 person-months), and GEM with 8.10 person-months (range, 7.93-9.38 person-months). Conclusions and Relevance: The results of this network meta-analysis support the relative short-term and long-term outcomes associated with first-line chemotherapy for metastatic pancreatic cancer used clinically in Japan.