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Cost-Effectiveness of Neoadjuvant/Adjuvant Treatment Strategies for HER2-Positive Breast Cancer


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In a study reported in JAMA Network Open, Kunst et al compared five neoadjuvant-adjuvant treatment strategies for patients with HER2-positive breast cancer and identified one that was associated with both improved outcomes and cost savings. The researchers found that a strategy of neoadjuvant paclitaxel, trastuzumab, and pertuzumab followed by either adjuvant trastuzumab in patients with pathologic complete response or by adjuvant dose-dense anthracycline-cyclophosphamide plus trastuzumab emtansine (T-DM1) in those with residual disease was associated with the greatest quality-adjusted life years gained and lowest cost compared with other strategies in women with HER2-positive breast cancer.

Study Details

The study involved development of a model to evaluate different neoadjuvant plus adjuvant strategies for treatment of women with HER2-positive breast cancer from a U.S. health-care payer perspective. The model was developed using data from the KATHERINE trial, other clinical trials with regimens that differed from those of KATHERINE, the Flatiron Health Database, McKesson Corporation data, and other evidence from published literature. Costs were expressed in 2020 U.S. dollars.

The model simulated patients receiving different neoadjuvant/adjuvant treatment strategies. All patients with a pathologic complete response irrespective of neoadjuvant regimen received adjuvant trastuzuamb (a component of each strategy). Patients with residual disease received one of five adjuvant therapies based on the neoadjuvant regimen:

  1. Neoadjuvant dose-dense anthracycline-cyclophosphamide and paclitaxel, trastuzumab, and pertuzumab followed by adjuvant trastuzumab
  2. Neoadjuvant dose-dense anthracycline-cyclophosphamide and paclitaxel, trastuzumab, and pertuzumab followed by adjuvant T-DM1
  3. Neoadjuvant paclitaxel, trastuzumab, and pertuzumab followed by adjuvant dose-dense anthracycline-cyclophosphamide plus T-DM1
  4. Neoadjuvant trastuzumab plus pertuzumab followed by adjuvant dose-dense anthracycline-cyclophosphamide and paclitaxel, trastuzumab, and pertuzumab plus T-DM1
  5. Neoadjuvant docetaxel and carboplatin plus trastuzumab and pertuzumab followed by adjuvant T-DM1.

Key Findings

Strategy 3 (adjuvant trastuzumab in patients with a pathologic complete response and neoadjuvant paclitaxel, trastuzumab, and pertuzumab followed by adjuvant dose-dense anthracycline-cyclophosphamide plus T-DM1 in those with residual disease) was associated with the highest quality-adjusted life years (10.73) and lowest lifetime costs ($415,833). It was considered the optimal strategy in terms of incremental cost-effectiveness, dominating all other strategies.

Strategies 5 and 4 had the next highest quality-adjusted life years (10.66 and 10.31), but they were associated with greater cost vs strategy 3 ($489,449 and $518,859).

Strategy 1 had the lowest quality-adjusted life years (9.67) and the third-lowest cost ($479,226). Strategy 2 had the second-lowest quality-adjusted life years (10.22) and second-lowest cost ($452,034).

Probabilistic analysis confirmed that strategy 3 had the highest probability of cost-effectiveness (> 70%) and was associated with the highest net monetary benefit across all willingness-to-pay thresholds from $0 to $200,000/quality-adjusted life years.

The investigators concluded: “These results suggest that neoadjuvant paclitaxel, trastuzumab, and pertuzumab followed by adjuvant trastuzumab for patients with pathologic complete response or followed by adjuvant dose-dense anthracycline-cyclophosphamide plus T-DM1 for patients with residual disease was associated with the highest health benefits and lowest costs for women with HER2-positive breast cancer compared with other treatment strategies considered.”

Lajos Pusztai, MD, DPhil, of Yale Cancer Center, Yale School of Medicine, is the corresponding author of the JAMA Network Open article.

Disclosure: For full disclosures of the study authors, visit jamanetwork.com.


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