Responses to subsequent anti-HER2 therapy after treatment with trastuzumab-DM1 in women with HER2-positive metastatic breast cancer

Abstract

Background: Women with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC) can respond to multiple lines of anti-HER2 therapy. It is unknown whether these patients will derive further clinical benefit following treatment with trastuzumab-MCC-DM1 (T-DM1).

Patients and methods: We retrospectively identified HER2-positive MBC patients treated with T-DM1 and characterized outcomes during subsequent lines of anti-HER2 therapy. Response was determined by a blinded radiology review. Time-dependent analyses were carried out using Kaplan-Meier estimates.

Results: We identified 23 patients treated with single-agent T-DM1 and report on the 20 patients who discontinued protocol therapy. All patients received trastuzumab-based metastatic therapy before initiation of T-DM1 [median 7 regimens (range 3-14)]. Of these 20 patients, 75% (15 of 20) received further therapy with or without anti-HER2 agents after discontinuing T-DM1. Partial response to either first- or second-subsequent line(s) of therapy was seen in 5 of 15 (33%) treated patients, including 33% (4 of 12) who received a regimen containing trastuzumab and/or lapatinib. Median durations of therapy to first- and second-subsequent regimens after T-DM1 were 5.5 and 6.4 months, respectively.

Conclusions: In heavily pretreated HER2-positive MBC patients, prior exposure to T-DM1 does not exhaust the potential benefit of ongoing anti-HER2 therapy with trastuzumab- and/or lapatinib-based regimens.

Figure 1.

Flow chart of observed patients. T-DM1, trastuzumab-MCC-DM1.

Figure 2.

Waterfall plot. Best response to either first- or second-subsequent line of therapy after T-DM1 by RECIST 1.1. Solid bars designate patients on trastuzumab- and/or lapatinib-based regimens. Striped bars designate patients who received non-trastuzumab- and non-lapatinib-based regimens only. Three patients did not have radiographic assessments; however, all three demonstrated clinically stable disease (as determined by review of clinical data) to first treatment after T-DM1. T-DM1, trastuzumab-MCC-DM1.

Figure 3.

Kaplan–Meier analysis of duration of therapy. Duration of therapy was defined from initiation of therapy until treatment discontinuation; for patients continuing on treatment, times were censored at date of last visit. Solid line designates the duration of therapy for the 15 patients who received a first-subsequent regimen after T-DM1. Dashed line designates the duration of therapy for the nine patients who went on to receive a second-subsequent regimen after T-DM1. T-DM1, trastuzumab-MCC-DM1.