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. 2021 Oct 27;21(1):1150.
doi: 10.1186/s12885-021-08894-2.

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

Luai S Al Rabadi  1 , Madeline M Cook  2 , Andy J Kaempf  3 , Megan M Saraceni  4 , Michael A Savin  1 , Zahi I Mitri  5
Affiliations

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

Luai S Al Rabadi et al. BMC Cancer. .

Abstract

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.

Keywords: Ado-Trastuzumab; Breast Cancer; HER2; Pertuzumab; T-DM1.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Progression free survival for pertuzumab pre-treated and pertuzumab-naive patients
Fig. 2
Fig. 2
Overall survival for pertuzumab pre-treated and pertuzumab-naive patients
See this image and copyright information in PMC

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