Abstract

The neoadjuvant treatment options for ERBB2-positive (also known as HER2-positive) breast cancer are associated with different rates of pathologic complete response (pCR). The KATHERINE trial showed that adjuvant trastuzumab emtansine (T-DM1) can reduce recurrence in patients with residual disease compared with patients treated with trastuzumab; however, T-DM1 and other ERBB2-targeted agents are costly, and understanding the costs and health consequences of various combinations of neoadjuvant followed by adjuvant treatments in the United States is needed. To examine the costs and disease outcomes associated with selection of various neoadjuvant followed by adjuvant treatment strategies for patients with ERBB2-positive breast cancer. In this economic evaluation, a decision-analytic model was developed to evaluate various neoadjuvant followed by adjuvant treatment strategies for women with ERBB2-positive breast cancer from a health care payer perspective in the United States. The model was informed by the KATHERINE trial, other clinical trials with different regimens from the KATHERINE trial, the Flatiron Health Database, McKesson Corporation data, and other evidence in the published literature. Starting trial median age for KATHERINE patients was 49 years (range, 24-79 years in T-DM1 arm and 23-80 years in trastuzumab arm). The model simulated patients receiving 5 different neoadjuvant followed by adjuvant treatment strategies. Data analyses were performed from March 2019 to August 2020. There were 4 neoadjuvant regimens: (1) HP: trastuzumab (H) plus pertuzumab (P), (2) THP: paclitaxel (T) plus H plus P, (3) DDAC-THP: dose-dense anthracycline/cyclophosphamide (DDAC) plus THP, (4) TCHP: docetaxel (T) plus carboplatin (C) plus HP. All patients with pCR, regardless of neoadjuvant regimen, received adjuvant H. Patients with residual disease received different adjuvant therapies depending on the neoadjuvant regimen according to the 5 following strategies: (1) neoadjuvant DDAC-THP followed by adjuvant H, (2) neoadjuvant DDAC-THP followed by adjuvant T-DM1, (3) neoadjuvant THP followed by adjuvant DDAC plus T-DM1, (4) neoadjuvant HP followed by adjuvant DDAC/THP plus T-DM1, or (5) neoadjuvant TCHP followed by adjuvant T-DM1. Lifetime costs in 2020 US dollars and quality-adjusted life-years (QALYs) were estimated for each treatment strategy, and incremental cost-effectiveness ratios were estimated. A strategy was classified as dominated if it was associated with fewer QALYs at higher costs than the alternative. In the base-case analysis, costs ranged from $415 833 (strategy 3) to $518 859 (strategy 4), and QALYs ranged from 9.67 (strategy 1) to 10.73 (strategy 3). Strategy 3 was associated with the highest health benefits (10.73 QALYs) and lowest costs ($415 833) and dominated all other strategies. Probabilistic analysis confirmed that this strategy had the highest probability of cost-effectiveness (>70% at willingness-to-pay thresholds of $0-200,000/QALY) and was associated with the highest net benefit. These results suggest that neoadjuvant THP followed by adjuvant H for patients with pCR or followed by adjuvant DDAC plus T-DM1 for patients with residual disease was associated with the highest health benefits and lowest costs for women with ERBB2-positive breast cancer compared with other treatment strategies considered.

Highlights

  • Preoperative chemotherapy in combination with ERBB2–targeted agents is increasingly used in the treatment of stage II to III ERBB2-positive breast cancer because this treatment strategy can lead to increased breast conservation and smaller resection volumes[1] and the extent of residual cancer can guide subsequent postoperative treatment.[2]

  • Patients with residual disease received different adjuvant therapies depending on the neoadjuvant regimen according to the 5 following strategies: (1) neoadjuvant dose-dense anthracycline/cyclophosphamide (DDAC)-THP followed by adjuvant H, (2) neoadjuvant DDAC-THP followed by adjuvant trastuzumab emtansine (T-DM1), (3) neoadjuvant THP followed by adjuvant DDAC plus T-DM1, (4) neoadjuvant trastuzumab and pertuzumab (HP) followed by adjuvant DDAC/THP plus T-DM1, or (5) neoadjuvant TCHP followed by adjuvant T-DM1

  • Probabilistic analysis confirmed that this strategy had the highest probability of cost-effectiveness (>70% at willingness-to-pay thresholds of $0-200,000/quality-adjusted lifeyears (QALYs)) and was associated with the highest net benefit. These results suggest that neoadjuvant THP followed by adjuvant H for patients with pathologic complete response (pCR) or followed by adjuvant DDAC plus T-DM1 for patients with residual disease was associated with the highest health benefits and lowest costs for women with ERBB2positive breast cancer compared with other treatment strategies considered

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Summary

Introduction

Preoperative (ie, neoadjuvant) chemotherapy in combination with ERBB2 ( known as growth factor receptor 2 [HER2])–targeted agents is increasingly used in the treatment of stage II to III ERBB2-positive breast cancer because this treatment strategy can lead to increased breast conservation and smaller resection volumes[1] and the extent of residual cancer can guide subsequent postoperative (ie, adjuvant) treatment.[2]. Trastuzumab and pertuzumab without any chemotherapy can result in 6% pCR rate in ER-positive/ERBB2-positive cancers,[5] whereas the combination of trastuzumab and pertuzumab with sequential anthracycline and taxane chemotherapy can result in pCR rates as high as 80% in ER-negative/ERBB2-positive cancers.[6,7] importantly, the decreased survival rates of patients with residual ERBB2-positive disease compared with individuals with pCR can be improved by additional, adjuvant therapy with trastuzumab emtansine (T-DM1). The KATHERINE trial[8] compared adjuvant T-DM1 with adjuvant trastuzumab in patients who had residual disease after neoadjuvant chemotherapy and ERBB2-targeted therapy. Of 1486 patients included in the trial (743 individuals in the T-DM1 arm and 743 individuals in the trastuzumab arm), all received a taxane, 1143 individuals (77%) received an anthracycline in the neoadjuvant setting, and 290 individuals (20%) received dual ERBB2-targeted therapy (eg, trastuzumab plus pertuzumab) concurrent with chemotherapy. These randomized clinical trials in different disease subtypes demonstrated the clinical principle that further adjuvant chemotherapy for patients with residual disease after neoadjuvant chemotherapy can improve outcome

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