Abstract P4-01-37: Discontinuation of HER2+ targeted therapy among cancer survivors with metastatic HER2+ breast cancer: A case report
Authors: Hui Lai Fong , Shah Nina N. , Hui Rita L. 
Published: March 2023

Background: Anti-HER2 directed therapy (aHER2tx) has significantly improved survival outcomes in patients with HER2-positive metastatic breast cancer (HMBC). Current United States (US) and European oncology practice guidelines recommend continuing aHER2tx until intolerable side effects or disease progression. It is estimated that 10-15% of treated patients (pts) may achieve prolonged complete remission (CR). Currently, the optimal duration of aHER2tx in patients achieving a CR is unknown. A PubMed literature search identified 7 case reports outside of the US that describe pts who remain in CR after discontinuation of aHER2tx. To our knowledge, this is the first analysis of similar cases in the US.

Method: We identified pts with a diagnosis of HMBC who discontinued aHER2tx between January 1, 2010, to June 30, 2021, at a large integrated healthcare system in the US. Pts were included if they had discontinued aHER2tx for at least one year. Data collection included demographics, histology, confirmed sites of metastatic disease (mets), local and systemic treatment (tx) before and after aHER2tx discontinuation, documented radiographic response, and reason to discontinue aHER2tx. Data collection ended on June 30, 2022.

Results: Our case report identified 15 pts (mean age at diagnosis 53.0 ± 13.2) based on inclusion criteria. Baseline demographics and characteristics are listed in Table 1. Common clinical characteristics of the cohort include mean age at mets diagnosis is 56 years, postmenopausal status (67%), invasive ductal carcinoma (87%), ER-negative (60%), HER2-positive 3+ by IHC (93%), de-novo mets (60%), multiple sites (93%) and multi-organ mets (87%). Among the cohort, 6 pts (40%) received prior adjuvant therapy, then later recurred, and of these only one had received HER2-based adjuvant tx. In all pts, first line therapy for mets included chemotherapy and aHER2tx, except one pt received endocrine therapy (ET) and aHER2tx. A CR was achieved in all but one pt (93%) with one line of aHER2tx consisting of trastuzumab (H) ± pertuzumab (P). One pt (7%) received local tx to all metastatic sites. In 13 pts, the median time to first radiologic complete response (RCR) after first line therapy for mets was 4 months (Interquartile (IQR) 3-15). Two cases were not included as we were unable to determine time to initial response after tx. All pts had confirmed RCR at the time of aHER2tx discontinuation. Median duration of aHER2tx was 8.3 years (IQR 4.8-9.5), including a median of 6.3 years (IQR 2.8-8.8) on maintenance aHER2tx. Twelve pts (80%) were off all therapy, and 3 pts (20%) continued ET for ER+ disease at the last follow-up (f/u). Patient preference (47%) was the most common reason for stopping aHER2tx. The median disease-free survival off aHER2tx was 4.8 years (IQR 3.1-6.2) and all pts were alive without evidence of disease at last f/u.

Conclusion: A subset of HMBC pts successfully discontinued aHER2tx without experiencing recurrence with a median of 4.8 years off therapy in a US cohort. In this case report, common clinical features like strong HER2 overexpression, no prior aHER2tx, and achieving RCR while on first line aHER2tx with H ± P are potential indicators for prolonged CR after discontinuing aHER2tx. Future studies with a comparator group are needed to fully understand the pt population who may safely stop aHER2tx after a CR.

Table 1: Baseline Demographics and Clinical Characteristics

Citation Format: Lai Fong Hui, Nina N. Shah, Rita L. Hui. Discontinuation of HER2+ targeted therapy among cancer survivors with metastatic HER2+ breast cancer: A case report [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-01-37.