Impact of Pertuzumab and Ado-Trastuzumab Emtansine on Cumulative Avoidance of Recurrence Among Women Treated for Locally Advanced, Inflammatory, or Early-Stage Nonmetastatic HER2-Positive Breast Cancer in the United States

Adv Ther. 2023 Sep;40(9):3857-3874. doi: 10.1007/s12325-023-02554-6. Epub 2023 Jun 26.

Abstract

Introduction: We assessed the impact of HER2-positive early breast cancer (EBC) treatment landscape changes following the introduction of pertuzumab and ado-trastuzumab emtansine (T-DM1) on cumulative population-level recurrences avoided since 2013 (first pertuzumab approval for EBC in the United States; US).

Methods: We constructed a multi-year epidemiologic population treatment-impact model to estimate annual recurrences between 2013 and 2031. Parameters were: BC incidence; stage I-III proportion; HER2-positive disease proportion; treatment proportions for neoadjuvant-only, adjuvant-only, and neoadjuvant-adjuvant continuation; and therapeutic agent proportions within each of those settings (chemotherapy only, trastuzumab ± chemotherapy, pertuzumab with trastuzumab ± chemotherapy, or T-DM1). The primary endpoint was cumulative recurrences, estimated by incorporating extrapolated clinical trial data for each regimen of interest into the model under four scenarios.

Results: Approximately 889,057 women were predicted to be diagnosed with stage I-III HER2-positive BC from 2006 to 2031 in the US and potentially indicated for HER2-targeted treatment. In steady-state equilibrium, the model estimated that real-world utilization of pertuzumab and T-DM1 will reduce the population-level number of recurrences by approximately 32%, with 7226 recurrences predicted in 2031 based on current utilization rates. In different modeled scenarios, use of neoadjuvant pertuzumab, continuation of pertuzumab in the adjuvant setting, and T-DM1 in the adjuvant setting in women with residual disease after neoadjuvant treatment were all predicted to reduce the number of recurrences.

Conclusion: Given the improvement of HER2-targeted treatments, alongside increases in BC disease burden, we expect that the population-level impact of HER2-targeted treatments will accelerate over the next decade. Our results suggest that utilization of HER2-targeted treatments in the US has the potential to change the epidemiology of HER2-positive EBC by preventing a substantial number of women from experiencing disease recurrence. These improvements may help to inform our understanding of the future disease and economic burden of HER2-positive BC in the US.

Keywords: Adjuvant; Ado-trastuzumab emtansine; Early breast cancer; HER2; Neoadjuvant; Pertuzumab; T-DM1; Treatment impact model.

Plain language summary

We predicted whether two treatments for a type of breast cancer called “HER2-positive,” that had not yet spread from the breast, could be used to avoid the cancer coming back in women in the United States (US), using computer modeling. The model estimated that approximately 889,057 women were predicted to be diagnosed with this type of breast cancer from 2006 to 2031, and that use of the treatments pertuzumab and ado-trastuzumab emtansine (T-DM1) would reduce the number of breast cancers that came back by around 32%. Treating with pertuzumab before surgery, continuing pertuzumab treatment after surgery, and giving T-DM1 after surgery (in the event that some of the breast cancer remained after being treated before surgery) were all predicted to reduce the number of breast cancers that come back. Overall, we expect use of pertuzumab and T-DM1 to keep lowering the number of breast cancers that come back over the next decade in the US.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Ado-Trastuzumab Emtansine / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Breast Neoplasms* / drug therapy
  • Breast Neoplasms* / pathology
  • Female
  • Humans
  • Neoplasm Recurrence, Local / drug therapy
  • Neoplasm Recurrence, Local / epidemiology
  • Neoplasm Recurrence, Local / prevention & control
  • Receptor, ErbB-2 / metabolism
  • Trastuzumab / therapeutic use
  • United States / epidemiology

Substances

  • Ado-Trastuzumab Emtansine
  • pertuzumab
  • Receptor, ErbB-2
  • Trastuzumab