Economic evaluation of the 70-gene prognosis-signature (MammaPrint®) in hormone receptor-positive, lymph node-negative, human epidermal growth factor receptor type 2-negative early stage breast cancer in Japan

Abstract

The 70-gene prognosis-signature is validated as a good predictor of recurrence for hormone receptor-positive (ER+), lymph node-negative (LN-), human epidermal growth factor receptor type 2-negative (HER2-) early stage breast cancer (ESBC) in Japanese patient population. Its high cost and potential in avoiding unnecessary adjuvant chemotherapy arouse interest in its economic impact. This study evaluates the cost-effectiveness of including the assay into Japan's social health insurance benefit package. An economic decision tree and Markov model under Japan's health system from the societal perspective is constructed with clinical evidence from the pool analysis of validation studies. One-way sensitivity analyses are also performed. Incremental cost-effectiveness ratio is estimated as ¥3,873,922/quality adjusted life year (QALY) (US$43,044/QALY), which is not more than the suggested social willingness-to-pay for one QALY gain from an innovative medical intervention in Japan, ¥5,000,000/QALY (US$55,556/QALY). However, sensitivity analyses show the instability of this estimation. The introduction of the assay into Japanese practice of ER+, LN-, HER2- ESBC treatment by including it to Japan's social health insurance benefit package has a reasonable chance to be judged as cost-effective and may be justified as an efficient deployment of finite health care resources.

Multigene assays and molecular markers in breast cancer: systematic review of health economic analyses

“…approaches to adjuvant therapy decision making. Similar findings were reported in the Japanese setting, where Kondo et al [46] investigated the cost-effectiveness of MammaPrint versus St. Gallen criteria from a societal perspective using an adaptation of a model previously used to evaluate the cost-effectiveness of Onco type DX ® . Projecting 10-year outcomes for a cohort of patients with ER+, LN− disease, aged 55 years at baseline from a Japanese cancer registry, MammaPrint was associated with an improvement in QALE of 0.06 QALYs and an additional cost of JPY 231,385 per patient, leading to an ICER of ~JPY 3.9 million (USD 43,000) per QALY gained.…”

“…: EUR 1,130 increase in direct costsVersus Adjuvant! : EUR 4,614 per QALY gainedCost savings driven by avoided chemotherapy, which was greater versus St. Gallen and resulted in dominance Kondo et al [46]85JapanLN−, ER+, HER2−0.048 years gained versus St. GallenSocietal costs were JPY 231,385 per patient higher with MammaPrint than with St. GallenJPY 4,820,813 per life year gained versus St. Gallen55-year-old patients from a Japanese cancer registry0.060 QALYs gained versus St. GallenJPY 3,873,922 per QALY gained versus St. Gallen (willingness to pay threshold from a societal perspective is JPY 5,000,000 (approx. USD 55,000) per QALY gained)Results were sensitive to changes in assumptions on risk classification (low versus high) and distant recurrence ratesMammaPrint budget impact studies Zarca et al [47]N/AFranceLN 1–2–Cost savings of EUR 9,043 per 100 patients per yearVersus current practice: MammaPrint is cost savingCost saving driven by reduced chemotherapy expenditureResults are sensitive to the relative use of St. Gallen and Adjuvant!MammaPrint versus Onco type DX ® cost-effectiveness studies Retèl et al [48]66NetherlandsTwo populations evaluated based on data previously collected by Thomassen et al and Fan et alThomassen: MammaPrint increased QALYs by 0.08 over Onco type DX ® Thomassen: Onco type DX ® increased direct cost by EUR 1,475Thomassen: MammaPrint dominates Onco type DX ® Fan: MammaPrint increased QALYs by 0.31 over Onco type DX ® Fan: Onco type DX ® increased direct cost by EUR 3,941Fan: MammaPrint dominates Onco type DX ® Uncertainty around these outcomes is high Yang et al [49]72USALN−, ER+MammaPrint increased QALYs by 0.097 over Onco type DX ® Oncotype DX ® increased direct cost by USD 6,284MammaPrint dominates Onco type DX ® Driver...…”

“…Four studies evaluated the cost-effectiveness of MammaPrint (Table 2) [43–46]. The 2010 article by Chen et al [44] reported that MammaPrint was likely to be cost-effective in the overall population, highly cost-effective in ER+ patients, but associated with reduced survival and quality-adjusted life expectancy (QALE) in patients with estrogen receptor negative (ER−) disease in the USA.…”

Personalizing the treatment of women with early breast cancer: highlights of the St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2013

“…These studies have yielded varying estimates ranging from cost-saving to an incremental cost-effectiveness ratio (ICER) of ∼US $60 000 per quality-adjusted life year (QALY). One Japanese study of the 70-gene assay [109] found an ICER of US $40 000 per QALY. Such assessments will be sensitive not only to the cost of the test, but to the net proportion of patients in whom testing leads to the omission of cytotoxic therapy, and to the cost of the cytotoxic regimen which would otherwise have been given.…”

Clinical utility of gene-expression profiling in women with early breast cancer: an overview of systematic reviews

“…In the subsequent sensitivity analysis in which the test was only administered to women with a Nottingham Prognostic Index of 3.4 or more, the ICER ranged from £6,053 to £29,569 per QALY gained compared with current practice. This uncertainty was also observed across the studies described by Rouzier et al 18 One study reported a decrease in direct costs of €7,430 compared with St. Gallen guidelines, 61 whereas two studies reported increases in direct cost of ¥231,385 62 and from $401 to $1,811 63 per patient compared with St. Gallen guidelines. Against Adjuvant!…”