Abstract P6-18-26: Ado-trastuzumab for the treatment of metastatic HER2-amplified breast cancer patients previously treated with pertuzumab
Authors: Al Rabadi LS , Kaempf A , Lim JY , Saraceni MM , Savin MA , Mitri ZI 
Published: May 2019

BACKGROUND: Ado-trastuzumab (T-DM1) is an antibody-drug conjugate of trastuzumab and a cytotoxic microtubule-inhibitory agent, emtansine. T-DM1 is approved for the treatment of advanced HER2-amplified breast cancer that progressed following trastuzumab-based therapies based on improvement in progression-free survival (PFS) and overall survival (OS) compared to the therapy of physician choice. However, T-DM1 trials were conducted prior to the widespread adoption of docetaxel, trastuzumab, and pertuzumab as standard frontline therapy for advanced HER2-amplified breast cancer. As such, none of the patients enrolled on T-DM1 studies had been exposed to pertuzumab, and the clinical benefit of T-DM1 in patients previously treated with pertuzumab therapy is unknown.

METHODS: We completed a retrospective review of patients at our institution over the age of 18 with metastatic HER2-amplified breast cancer treated with pertuzumab prior to T-DM1 between February 2013 and May 2018. Data was collected on patient and tumor characteristics, number and duration of therapies in the metastatic setting, and clinical outcomes. The primary endpoint of this study was PFS in patients given T-DM1 after earlier exposure to pertuzumab. Secondary endpoints included overall response rate (ORR), prolonged duration of T-DM1 therapy (&gt; 6 months), and OS. Adverse events following T-DM1 were collected using CTCAE 4.03, with a focus on cardiac dysfunction and peripheral neuropathy. Patient features and outcomes were summarized with descriptive statistics and time-to-event measures were analyzed using the Kaplan-Meier method and log-rank test.

RESULTS: Twenty patients met the inclusion criteria and are included in this study. The patient population consisted of 18 non-Hispanic white and 2 black women, with a median age of 58.5 (range 34-68) years. The number of prior systemic therapies (excluding pertuzumab) ranged from 0-8 with a median of 1 therapy. The duration of T-DM1 therapy (started, on average, 24 months after metastatic diagnosis) ranged from &lt; 1 month to 3.5 years with a median of 6 months. T-DM1 therapy was overall very well tolerated, with all adverse events being grade ≤2. Of note, 2 patients had grade 2 neuropathy, and one patient had grade 1 cardiotoxicity, without any change in left ventricular ejection.

Among 18 patients evaluable for response, ORR was 16.7% (95% CI: 3.6% to 41.4%), with 3 patients achieving a partial response. No complete responses were noted. 10/18 (55.6%) patients had prolonged duration of therapy with T-DM1. Median follow-up time after initiation of T-DM1 was 15 months and 6/20 (30%) patients died while under observation. At the time of data cut-off, 10/20 patients had disease progression on T-DM1. Median PFS was 16 months, with a 1-year PFS rate of 54.5% (95% CI: 36.4% to 81.7%). The 1-year OS rate was 75.0% (95% CI: 58.2% to 96.6%). Patients with liver metastases (n=8) had a significantly worse PFS (p=0.003).

CONCLUSION: T-DM1 following pertuzumab is well tolerated and shows excellent efficacy in the treatment of HER2-positive metastatic breast cancer. Comparing T-DM1 following pertuzumab to T-DM1 in pertuzumab-naïve patients should be explored in this patient population.

Citation Format: Al Rabadi LS, Kaempf A, Lim JY, Saraceni MM, Savin MA, Mitri ZI. Ado-trastuzumab for the treatment of metastatic HER2-amplified breast cancer patients previously treated with pertuzumab [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P6-18-26.