STOP-HER2: Stopping Trastuzumab in HER2+ MBC

Prior treatment

• Participants who are receiving any investigational agents to treat breast cancer

Other illness

• Participants with psychiatric illness/social situations that would limit compliance with study requirements.

Other

• All English- speaking patients will participate in the PRO measures. Patients that do not read or understand English are eligible to participate but will be exempt from the patient completed questionnaires

• Age ≥18 years
• Participants must have histologically or cytologically confirmed unresectable locally advanced or metastatic invasive breast carcinoma that is HER2-positive by American Society of Clinical Oncology/College of American Pathologists 2018 criteria, as assessed by standard institutional guidelines (central testing is not required). Both estrogen receptor (ER)-positive/HER2-positive and ER-negative/HER2-positive will be eligible.
• Participants with ER-positive disease should continue endocrine therapy.
• Participants must be currently receiving first-line anti-HER2 therapy (any regimen) for metastatic disease and must have been on this therapy for at least 3 years without evidence of progressive disease according to RECIST 1.1 criteria. The following exceptions apply:
• Patients with history of brain-only progressive disease previously treated with local therapy (surgery and/or radiation therapy) are eligible, provided they meet all the following study criteria:
  • Asymptomatic
  • Not requiring anti-convulsant for symptomatic control
  • Not requiring corticosteroids
  • No evidence of interim central nervous system (CNS) progression between the completion of CNS-directed therapy and screening radiographic study
  • Minimum of 2 years (24 months) between completion of CNS-directed therapy and study start
• Participants with history of oligo-progression (i.e., progressive disease of a single lesion) outside CNS treated with local treatment and/or change of endocrine therapy only are eligible, provided they meet the following criteria:
  • No evidence of interval progression between completion of local treatment or endocrine therapy change and screening radiographic study
  • Minimum 2 years (24 months) between completion of local therapy or treatment switch and study start
• CT scan within 30 days of study start without definite evidence of progressive disease in the opinion of the treating investigator.
• Available, representative archival formalin-fixed paraffin-embedded (FFPE) tumor tissue block from primary and/or metastatic site. If tissue block is unavailable, 20 unstained 10uM slides will be accepted (less than 20 slides may be acceptable with documentation of Sponsor-Investigator approval and would not require an eligibility exception). Tumor tissue must be received by coordinating site prior to study enrollment.
• ECOG performance status 0-1
• For intervention arm only (cohort 2): willingness to stop anti-HER2 systemic therapy
• Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures
• Ability to understand the study requirements and document informed consent indicating awareness of the investigational nature and the risks of this study
• Participants with another prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of this trial are eligible