Abstract P6-11-11: Trastuzumab beyond Progression in HER2-Positive Advanced Breast Cancer: The Royal Marsden Experience

Abstract

Abstract Background: Routine clinical practice and a growing body of evidence support the continuation of trastuzumab (T) in patients with HER-2 positive (+ve) advanced breast cancer progressing on previous T-based therapy. Despite this, recent UK clinical guidance advises against continuing T on evidence of disease progression (PD) in the absence of brain metastases. This retrospective study therefore evaluated the outcome of patients (pts) with HER-2+ve locally advanced (LA) or metastatic breast cancer (MBC) who continued T beyond PD, treated in our Unit. Patients and methods: HER-2+ve pts receiving T for LA or MBC were identified from our prospectively maintained database and pharmacy records. Those receiving T beyond PD after adjuvant or one line of T for advanced disease were assessed for response and outcome. From thetimepoint of T continuation beyond PD we calculated the overall disease control rate (response or stable disease), time to progression (TTP), and overall survival (OS). Results: 114 pts with HER-2+ve LA or MBC treated with T beyond PD were identified. At the time of analysis 35 (31%) pts were still alive with a median follow up of 20 months (mo). The main site of disease was visceral in 84 (74%) pts, including 37 (32%) pts with CNS involvement. 30 (26%) pts had soft tissue or bone metastases only. Fifty nine (52%) pts had received adjuvant chemotherapy and 13 (11%) pts had received adjuvant T. Seventy six (66%) pts had 1 line of chemotherapy prior to continuation of T beyond PD and 21 (19%) had 2 or more lines. Fifty three (46%) pts had previously received taxanes + T for their LA or MBC. Post-progression, 66 (58%) pts received T combined with chemotherapy; 12 (11%) taxane-based, 32 (28%) capecitabine and 22 (19%) vinorelbine. Information regarding response was not available in 21(18%) pts. Of the ninety three (82%) pts with documented clinical (n=16) or radiological (n=77) response evaluation, 68 (60%) pts were considered as having stable disease (SD) or better and 25 (22%) as having PD. The median duration of T was 10 mo (95% CI: 8-11 mo), the median TTP was 24wks (95% CI: 21-28 wks) and the median OS was 19 mo (95% CI:12-24mo). In a sub-group analysis of the 81(71%) pts who received T as first-line Rx or relapsed within 12 wks of adjuvant T, overall disease control was achieved in 50 (61%) pts, the median TTP was 25wks (95% CI:18-33 wks) and the median OS was 22 mo(95% CI:17-27mo). In terms of safety, only 6 (5%) pts overall had to discontinue T secondary to decline in left ventricular ejection fraction. Conclusion: Our results from an unselected group of patients are supported by positive results from other studies and provide additional evidence that continuation of trastuzumab beyond disease progression is of clinical benefit. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P6-11-11.