Abstract PD10-05: Cost-effectiveness of different neoadjuvant followed by adjuvant treatment combination strategies for women with HER2-positive breast cancer
Authors: Kunst Natalia R. , Wang Shi-Yi , Hood Annette , Mougalian Sarah , DiGiovanna Michael P. , Adelson Kerin , Pusztai Lajos 
Published: March 2020

Abstract
Background: Several neoadjuvant and adjuvant treatment options exist for patients with HER2-positive (HER2+) stage II-III breast cancer. Recent results of the KATHERINE trial (NCT01772472) showed that adjuvant T-DM1 can reduce distant recurrence risk in patients without pathologic complete response (pCR) after neoadjuvant chemotherapy. However, pCR rates can range between 20-80% depending on treatment regimen and subtype. Given the high cost of T-DM1 and other HER2-targeted agents, understanding the relationship between the costs and health consequences of various neoadjuvant-adjuvant treatment combinations is needed. Our goal is to identify the treatment strategy that leads to the highest health benefit (i.e., lowest distant recurrence risk) at the least costs.
Methods: We developed a decision-analytic Markov model to simulate clinical practice in a cohort of women aged ≥49 with HER2+ breast cancer similar to the KATHERINE trial population. We considered 4 neoadjuvant regimens: HP: trastuzumab (H) and pertuzumab (P) doublet; THP: paclitaxel (T), H and P triplet; ddAC/THP: dose dense anthracycline/cyclophosphamide (ddAC) followed by T, H, P; TCHP: docetaxel (T), carboplatin (C), H, and P, and 4 adjuvant treatments for patients with residual disease including: H; T-DM1; ddAC/THP followed by T-DM1; and ddAC followed by T-DM1. We combined these neoadjuvant and adjuvant treatment options to mimic four clinically plausible treatment de-escalation strategies and examined their cost effectiveness. All patients with pCR after any neoadjuvant treatment received adjuvant H. Strategies for residual disease: 1: neoadjuvant-ddAC/THP+adjuvant-H; 2: neoadjuvant-ddAC/THP+adjuvant-T-DM1; 3: neoadjuvant-THP+adjuvant-ddAC followed by T-DM1; 4: neoadjuvant-HP+adjuvant-ddAC/THP followed by T-DM1; 5: neoadjuvant-TCHP+adjuvant-T-DM1. We informed the effectiveness, cost and utility parameters from the KATHERINE trial, McKesson data, and published literature. We estimated costs and quality-adjusted life years (QALYs) over a lifetime for each strategy, and an incremental cost-effectiveness ratio (ICER), from a healthcare payer perspective and addressed the uncertainty with a probabilistic sensitivity analysis (PSA).
Results: The mean per-patient costs varied between $274,550 (Strategy 3) and $354,652 (Strategy 4) and the mean per-patient QALYs varied between 9.44 (Strategy 1) and 10.56 (Strategy 3). When considering the five treatment strategies, Strategy 3 yielded a substantial gain in QALYs at decreased costs, representing the dominating strategy. The decision-analytic model identified Strategies 1, 2, 4 and 5 to be cost-ineffective due to their lower health effects and higher costs (i.e., dominated strategies). PSA indicated Strategy 3 to have the highest probability of cost-effectiveness and expected net benefit across a wide range of willingness-to-pay thresholds ($0-250,000). These findings persisted when changing a number of assumptions, including increasing starting age and varying pCR rates and distant recurrence probability after an initial local recurrence.
Conclusions: Our study indicates that neoadjuvant trastuzumab+paclitaxel+pertuzumab followed by adjuvant trastuzumab for patients with pCR (around 46% of patients) and by adjuvant ddAC and T-DM1 for those with residual disease is the most cost-effective treatment strategy for women with HER2+, stage II-III breast cancer.
StrategyCostsQALYsICERStrategy 3 Neoadjuvant T, H, P Adjuvant ddAC+T-DM1 for RD; H for pCR$274,55010.56-Strategy 1 Neoadjuvant T, H, P, ddAC Adjuvant H for RD; H for pCR$278,8829.44DominatedStrategy 2 Neoadjuvant T, H, P, ddAC Adjuvant T-DM1 for RD; H for pCR$293,98210.04DominatedStrategy 5 Neoadjuvant T, C, H, P Adjuvant T-DM1 for RD; H for pCR$316,26610.46DominatedStrategy 4 Neoadjuvant H, P Adjuvant T, H, P, ddAC+T-DM1 for RD; H for pCR$354,65210.15Dominated* “Dominated” strategy leads to fewer QALYs at higher costs than the next least costly treatment alternative.
Citation Format: Natalia R. Kunst, Shi-Yi Wang, Annette Hood, Sarah Mougalian, Michael P. DiGiovanna, Kerin Adelson, Lajos Pusztai. Cost-effectiveness of different neoadjuvant followed by adjuvant treatment combination strategies for women with HER2-positive breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr PD10-05.