Abstract PS1-10-20: Free-her: discontinuation of maintenance her-2 directed therapy in long-term survivors of metastatic her-2 positive breast cancer: a trial update

Abstract Introduction: While metastatic breast cancer (BC) is considered an incurable disease, with the advent of HER-2directed therapy, a subset of patients with metastatic HER-2 positive (HER2+) BC maintain a completeremission for years. The current standard of care in the US for these patients is to continue anti-HER-2therapy indefinitely, with its associated toxicity, cost, and inconvenience. This study seeks to determinethe feasibility of discontinuing Her-2 directed therapy while maintaining remission and the possibility ofcure in patients who have remained in complete radiographic remission (CRR) of their metastatic HER2+BC for at least 36 months. Here, we provide a trial update. Methods: This is an IRB-approved, single-site pilot study that seeks to enroll 20 subjects with stage IV HER2+ BCin CRR for at least 36 months who have negative peripheral blood ctDNA at the time of enrollment.Financial toxicity and QOL assessments are also being performed. Study patients are monitored withctDNA testing at 6 and 12 weeks after treatment discontinuation, and once every 12 weeks thereafter.Standard of care radiologic imaging also occurs at 3 months after treatment discontinuation and thenevery 6 months thereafter. Patients are continued on study for a total of three years or until evidence ofdisease recurrence, defined as ctDNA positivity or radiographic progression of disease. If patients hadhormone receptor positive (HR+) disease, they are recommended to continue hormonal treatment duringthe trial. Results: At the time of this report, 14 patients have been enrolled. The median subject age at enrollment is 64.5(range 41-86), and the median duration of CRR prior to enrollment was 6 years (range 3-17). Eightpatients had de novo metastatic disease, and 5 had relapsed metastatic disease, with a median time of 6years between diagnosis of localized disease and the development of metastatic disease. Eleven of the14 patients were HER2 3+ on IHC, and 3 were 2+ on IHC and FISH positive. Ten of the 14 were alsoHR+. Only 6 patients had adequate tissue for the tumor-informed Signatera assay. The other 8 patientswere evaluated using Guardant Reveal assay.At baseline, 10 of the 14 had oligometastatic disease, defined as fewer than 5 metastatic sites. Sites ofmetastases included bone (8), distant lymph nodes (3), lung (2), liver (2), and brain (2). The majority ofpatients (11) had induction therapy with docetaxel, trastuzumab and pertuzumab (HP) and maintenanceHP, but 3 patients had no cytotoxic therapy and only targeted therapy for their metastatic disease.Of the 9 patients with de novo metastatic disease, 7 had local therapy to the primary breast lesion. Twopatients had local therapy (surgery and/or radiation) to all sites of disease; three had no local therapy atall.At the time of this report, only 2 patients have developed a positive ctDNA with one detected at 12 weeksoff therapy and one at 60 weeks. Both patients had oligometastatic disease. The patient relapsing at 12weeks had been in CRR for 4.5 years and had ER negative disease. After re-initiating anti-HER-2therapy (HP), she has remained ctDNA intermittently positive but in CRR for 18 months. The patient with ctDNA positivity at 60 weeks reverted to ctDNA negative without re-initiating therapy and has remainedctDNA negative with no clinical evidence of disease for 9 months.The maximum length of time on trial for any patient in the study is 24 months. No deaths have occurredon trial. Conclusions: Our current data suggest that HER2-directed maintenance therapy can safely be discontinued in patientswith metastatic HER2+ BC who have remained in CRR for at least 36 months. Baseline ctDNA testingmay be useful to select patients who may safely discontinue therapy and to closely monitor those patientsfor continued remission. Citation Format: E. Krill Jackson, F. valdes, C. Calfa, T. King, A. Perez. Free-her: discontinuation of maintenance her-2 directed therapy in long-term survivors of metastatic her-2 positive breast cancer: a trial update abstract. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS1-10-20.