Abstract PO3-04-04: Long term survival of metastatic HER2 positive breast cancer patients with no radiographic evidence of disease (NED) on HER2 antibody therapy
Authors: Bennett Alexis , Chen Zhengyi , Martin James , Mallat Naji , Fu Pingfu , Montero Alberto 
Published: May 2024

Abstract
Introduction A small proportion of women with human epidermal growth receptor 2 (HER2) positive metastatic breast cancer (mBC) achieve “no evidence of disease” (NED) status with HER2 monoclonal antibody therapy. Patients who achieve NED status have excellent long term outcomes with overall (OS) and progression free survival (PFS) rates greater than 95%. Presently there are no reliable biologic or clinical factors which are predictive of NED. It is also unclear in NED patients when it would be safe to discontinue therapy. Therefore, even in HER2+ mBC NED patients, HER2 therapy is often continued indefinitely. In this study, we characterize clinical outcomes in HER2+ mBC patients who achieved NED status and received HER2 antibody therapy for 5+ years. Methods We conducted a retrospective analysis of patients at a U.S. academic medical center. Patients with HER2+ mBC who had received at least 5 years of either trastuzumab or trastuzumab/pertuzumab (from 2014- 2023) were identified for our NED cohort. For a non-NED comparator group, we identified women with stage IV HER2+ mBC from the tumor registry (from 2012-2021). Descriptive statistics were used to describe the demographic information and clinical characteristics. Kaplan-Meier method with log-rank test was used to analyze OS and PFS between both patient cohorts. Results 102 patients were identified that received trastuzumab or trastuzumab/pertuzumab for 5+ years. From this group, 33 patients were identified as NED based on clinical documentation and imaging. From our tumor registry data, there were 58 stage IV HER2+ patients. 34 patients met inclusion criteria for our non-NED cohort. The median follow-up time was 132 (range: 39 - 296) months for the NED cohort and 26 (range: 1-99) months for the non-NED cohort. The average diagnosis age was significantly older for the NED cohort (61 vs. 52 years, P=0.001). No other significant differences with respect to hormone receptor expression, race, or the presence of brain metastases were observed between groups. With respect to HER2 therapy, 61% of NED patients had received trastuzumab alone, and 39% trastuzumab/pertuzumab. By contrast in the non-NED cohort most received trastuzumab/pertuzumab (59%). The median time on HER2 therapy for the NED group was 125 months—70% of patients in the NED cohort were still receiving therapy vs, 12% for the non-NED cohort. As expected, the median OS (NR vs. 25.5 months; P&lt; 0.0001) and PFS (NR vs. 7.9 months; P&lt; 0.0001) were significantly longer in the NED cohort. 5 and 10 year OS rates for the NED cohort were 90.5% (95% confidence interval (CI): 80.8-100%) and 87% (95% CI: 75.9-99.8%), respectively. By contrast, for the non-NED cohort 5 and 10 year OS rates were only 21.3% (95% CI: 11.06-41.1%) and 0% (95% CI: 0-0%), respectively. 5 and 10 year PFS rates were 84.1% (95% CI: 72.2-97.9%) and 76.6% (95% CI: 67.7-93.6%), respectively for the NED cohort, and both were 0% for the non-NED cohort. The presence of brain metastases in the NED cohort was associated with reduced 5 and 10 year OS rates: 60% (95% CI: 29.3-100%) and 40% (95% CI: 13.7-100%), respectively. We observed in the NED cohort was associated with a drop in ejection fraction and clinically significant heart failure in 24% of patients while on HER2 therapy. Conclusions HER2+ mBC patients who achieve NED status have an excellent prognosis with starkly different clinical outcomes compared to HER2+ mBC patients who do not. We observed that 10 year OS rates in HER2+ NED patients was approximately 90%, which did not differ from 5 year OS rates. This suggests that HER2 therapy could be potentially discontinued after 5 years in mBC patients who achieve NED. More studies are needed to develop robust predictive markers for patients likely to achieve NED with HER2 targeted therapy.
Citation Format: Alexis Bennett, Zhengyi Chen, James Martin, Naji Mallat, Pingfu Fu, Alberto Montero. Long term survival of metastatic HER2 positive breast cancer patients with no radiographic evidence of disease (NED) on HER2 antibody therapy [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-04-04.