The phase III KATHERINE trial showed that trastuzumab emtansine (T-DM1) significantly improved invasive disease-free survival (iDFS) compared to trastuzumab in the adjuvant treatment of patients with residual invasive human epidermal growth factor receptor 2-positive (HER2+) early breast cancer (EBC), who received neoadjuvant therapy containing taxanes and trastuzumab. This study evaluated the cost-effectiveness of adjuvant T-DM1 versus trastuzumab for patients in Singapore with HER2+ EBC after neoadjuvant therapy.
A six-state Markov model (iDFS, non-metastatic recurrence, remission, first-line metastatic, subsequent line metastatic, death) was developed from the Singapore healthcare system perspective, with a 35-year time horizon. Clinical inputs and utilities were derived from KATHERINE (iDFS) and from published literature (other health states). Direct costs were obtained from government sources and published literature. Model outputs were: costs; life-years (Lys); quality-adjusted Lys (QALYs); incremental cost-effectiveness ratios (ICERs). Sensitivity/scenario analyses explored uncertainties.
The base case projected increased costs by S$64,458, improved outcomes by 1.726 Lys and 1.661 QALYs, and an ICER of S$38,818/QALY. A higher proportion of patients on T-DM1 remained in iDFS at 10 years compared to patients on trastuzumab (76% versus 63%). Assuming a longer time horizon or T-DM1 treatment effect reduced the ICER. In deterministic sensitivity analyses, the ICER was most sensitive to: metastatic recurrence proportion; maximum cure proportion; time horizon. Probabilistic sensitivity analyses showed T-DM1 had a 96.5% probability of being cost-effective at a willingness-to-pay threshold of S$75,000/QALY.
Compared to trastuzumab, patients with HER2+ EBC receiving T-DM1 in the adjuvant setting spent longer in iDFS, contributing to cost-offsets driven by avoidance of care costs in the metastatic health states together with improved patient outcomes. The resulting ICER suggests cost-effectiveness of adjuvant T-DM1 in the Singapore setting.
Roche Singapore Pte Ltd.
Roche Singapore Pte Ltd.
E.H. Lim: Financial Interests, Personal and Institutional, Advisory Board: Roche Singapore Pte Ltd., Novartis, DKSH, Eisai, Eli Lilly. A. Lim: Financial Interests, Institutional, Advisory Role: a. Roche Singapore Pte Ltd. J.S. Khara: Financial Interests, Personal, Full or part-time Employment: Roche Singapore Pte Ltd.; Financial Interests, Personal, Stocks/Shares: Roche Singapore Pte Ltd. J. Cheong: Financial Interests, Personal, Full or part-time Employment: Roche Singapore Pte Ltd.; Financial Interests, Personal, Stocks/Shares: Roche Singapore Pte Ltd. J. Fong: Financial Interests, Personal, Full or part-time Employment: Roche Singapore Pte Ltd.; Financial Interests, Personal, Stocks/Shares: Roche Singapore Pte Ltd. S. Sivanesan: Financial Interests, Personal, Full or part-time Employment: Roche Singapore Pte Ltd.; Financial Interests, Personal, Stocks/Shares: Roche Singapore Pte Ltd. M. Griffiths: Financial Interests, Institutional, Advisory Role: Roche Singapore Pte Ltd. E. New: Financial Interests, Institutional, Advisory Role: Roche Singapore Pte Ltd. S.C. Lee: Financial Interests, Personal and Institutional, Research Grant: Pfizer, Eisai, Taiho, ACT Genomics, Karyopharm, Epizyme, Adagene, MSD; Financial Interests, Personal and Institutional, Advisory Board: Pfizer, Eisai, ACT Genomics, Novartis, AstraZeneca, Eli Lilly, MSD, Roche Singapore Pte Ltd., Daiichi Sankyo; Financial Interests, Personal and Institutional, Invited Speaker: Pfizer, Eisai, ACT Genomics, Novartis, AstraZeneca, Eli Lilly, MSD, Roche Singapore Pte Ltd.