Abstract P3-14-08: Responses to Subsequent Anti-HER2 Therapy after Treatment with Trastuzumab-DM1 in Women with HER2-Positive Metastatic Breast Cancer

Abstract

Abstract Background: Women with HER2-positive metastatic breast cancer (MBC) can have clinical responses to multiple lines of anti-HER2 therapy. However, it is unknown whether these patients will derive further clinical benefit following treatment with the novel antibody-drug conjugate trastuzumab-MCC-DM1 (T-DM1), which has significant activity in trastuzumab-refractory breast cancer. Methods: We retrospectively identified patients treated with T-DM1 monotherapy on clinical trials for HER2-positive MBC at Dana-Farber Cancer Institute and characterized clinical outcomes during subsequent lines of anti-HER2 therapy. Response was determined by an independent and blinded radiology review using modified RECIST 1.1 criteria without confirmatory scans; patients without radiologic assessment were considered non-responders. Duration of therapy was defined from initiation of therapy until treatment discontinuation, and for patients continuing on therapy, times were censored at date of last visit; analysis was performed using Kaplan-Meier estimates. Results: We identified 23 patients treated on protocol-based therapy with single-agent TDM-1 and report on the 20 patients who had discontinued protocol, and hence, T-DM1 therapy. All patients received trastuzumab in the metastatic setting prior to initiation of T-DM1, with a median number of 6 (range 1-14) prior regimens. Most (75%) were taken off study secondary to progressive disease and the remainder discontinued therapy for toxicity. Of these 20 patients, 75% (15 of 20) received further therapy with or without anti-HER2 agents after concluding T-DM1; reasons for not receiving additional treatment after T-DM1 include death (3) and interruption of therapy due to physician or patient request (2). The majority (12 of 15; 80%) of patients treated beyond T-DM1 received a regimen containing either trastuzumab and/or lapatinib at some point during their course. 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 (Figure 1). Three patients did not have radiographic assessments; however, all 3 demonstrated clinically stable disease (as determined by review of clinical data) to first treatment after T-DM1. Median duration of therapy to first-subsequent regimen after T-DM1 was 5.5 months. Of the 9 patients that received a second-subsequent regimen, the median duration of therapy to the second-subsequent treatment was 6.4 months. 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. Maximum Decrease in Target Lesion Diameter Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P3-14-08.