Ado-trastuzumab for the treatment of metastatic HER2-positive breast cancer in patients previously treated with Pertuzumab

Luai S. Al Rabadi, Madeline M. Cook, Andy J. Kaempf, Megan M. Saraceni, Michael A. Savin, Zahi I. Mitri

Research output: Contribution to journalArticlepeer-review


Background: Docetaxel in combination with two HER2-directed therapies, trastuzumab and pertuzumab, is the current standard frontline therapy for patients with metastatic HER2-positive breast cancer. Ado-trastuzumab (T-DM1), an antibody-drug conjugate of trastuzumab and a cytotoxic microtubule-inhibitory agent, emtansine, is approved in patients that have progressed with prior trastuzumab-based therapy. However, the benefit of T-DM1 in patients previously treated with pertuzumab therapy for metastatic breast cancer remains unclear. Methods: We identified thirty-three adults with metastatic HER2-positive breast cancer treated between March 2013 and July 2018 with T-DM1 either as subsequent therapy after progression on a pertuzumab-based regimen (i.e., “pertuzumab-pretreated”) or without prior exposure to pertuzumab (i.e., “pertuzumab-naïve”). Collected data included patient demographics, treatment history, adverse events, and clinical outcomes. For both cohorts receiving T-DM1, the primary endpoint was PFS and secondary endpoints were overall survival (OS), overall response rate (ORR), clinical benefit rate (CBR), and T-DM1-related toxicity rate. Results: Pertuzumab-pretreated patients (n = 23, with 21 evaluable for T-DM1 efficacy) had a median PFS of 9.5 months (95% CI: 2.9–NA), 1-year OS rate of 67.4% (95% CI: 50.0–90.9%) with an unreached median, ORR of 14.3% (95% CI: 3.0–36.3%), and CBR of 52.4% (95% CI: 29.8–74.3%), with none of these measures being statistically different than those estimated for the pertuzumab-naïve group (n = 10). Treatment with T-DM1 after prior pertuzumab exposure (median T-DM1 duration 2.9 months) resulted in no grade ≥ 3 adverse events. Conclusions: In our cohort, prior exposure to pertuzumab did not significantly impact T-DM1’s clinical efficacy or safety profile as second- or later-line therapy in patients with metastatic HER2-positive breast cancer.

Original languageEnglish (US)
Article number1150
JournalBMC cancer
Issue number1
StatePublished - Dec 2021


  • Ado-Trastuzumab
  • Breast Cancer
  • HER2
  • Pertuzumab
  • T-DM1

ASJC Scopus subject areas

  • Oncology
  • Genetics
  • Cancer Research


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