Abstract P2-15-04: Trastuzumab re-treatment following adjuvant trastuzumab and the importance of distant disease-free interval: The HERA trial experience

Abstract

Abstract Background: Trastuzumab (T) forms the backbone of the current first-line treatment of advanced HER2+ breast cancer. In the present study we sought to evaluate the impact of the time interval between the end of adjuvant trastuzumab and distant recurrence (TDRI), upon a) overall survival (OS), b) the duration of trastuzumab-based regimens (T) in the advanced setting. Patients & Methods: a) The first hypothesis involved 187 pts on HERA treated with adjuvant T and diagnosed with distant recurrence after the scheduled treatment period of 1 year at 4 years median follow-up. The impact of TDRI on OS from distant recurrence was evaluated in a Cox model adjusted for tumor size, nodal and hormone receptor status at time of enrollment into the HERA trial. b) The second hypothesis involved 90 patients retreated with T in the metastatic setting. A questionnaire was sent to investigators retreating pts with T upon distant recurrence; 144 of 156 questionnaires were returned (93%), and 90 pts were selected based on available clinical information and consent for subsequent studies (14 pts were randomized to observation and received adjuvant trastuzumab after crossover). Results: a) There was no statistically significant relationship between TDRI following 1yT and OS from distant recurrence: HR 0.99, p = 0.46; HR 0.99, p = 0.27 from the stratified and unadjusted Cox proportional hazard models, respectively. The median OS from distant recurrence was numerically longer among pts with a TDRI of ≥ 12 months (n = 103) than < 12 months (n = 84) but not statistically significant (23.7 vs. 17.8 months, p = 0.47). b) The median duration of T-based regimens for metastatic disease was 8.8 months (n = 88), 9.4 months in the ER+ cohort (n = 36) and 8.8 months in the ER- cohort (n = 52); (n = 2, missing). Sites of first distant recurrence and subsequent disease progression for the 90 pts were hierarchically distributed as below. First distant recurrence n (%)Subsequent progression n (%)CNS6 (6.7%)22 (24.4%)Visceral45 (50.0%)39 (43.3%)Skeletal25 (27.8%)9 (10.0%)Soft Tissue14 (15.6%)9 (10.0%)No event-11 (12.2%) Conclusions: In the HERA trial, TDRI following 1yT did not impact on OS from distant recurrence in pts experiencing distant disease recurrence. This may be due to the benefit of anti-HER2 regimens in subsequent lines of therapy. Although our sample size is limited, the present analysis suggests that pts experiencing a shorter interval (≤ 12 months) from the end of adjuvant trastuzumab to distant recurrence derive similar benefit from trastuzumab-containing regimens in the metastatic setting when compared to the cohort with an interval > 12 months. CNS relapse in HER2-postive breast cancer remains a clinical problem. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P2-15-04.