PRIMARY OBJECTIVES:
I. To evaluate the 1-year progression-free survival (PFS) in participants with HER2-positive metastatic breast cancer (MBC) and exceptional response to anti-HER2 therapy who agree to stop anti-HER2 therapy (cohort 2).
II. To evaluate 1-year PFS in participants with HER2-positive MBC and exceptional response to anti-HER2 therapy continuing anti-HER2 therapy (cohort 1).
SECONDARY OBJECTIVES:
I. To determine the clinical benefit rate (CBR) of re-initiation of anti-HER2 therapy for participants who experience disease progression after stopping anti-HER2 therapy.
II. To determine 3-year overall survival (OS) in participants in cohorts 1 and 2.
III. To determine 3-year PFS in participants in cohorts 1 and 2.
IV. To determine the probability of restarting anti-HER2 therapy without progression of disease in participants stopping anti-HER2 therapy.
EXPLORATORY OBJECTIVES:
I. To characterize the clinical and biological profile of persistent remission (i.e., maintained response or disease stability according to Response Evaluation Criteria in Solid Tumors [RECIST 1.1] criteria) in participants stopping anti-HER2 therapy.
II. To characterize the clinical and biological profile of disease recurrence in participants stopping anti-HER2 therapy.
III. To determine saved treatment costs in participants stopping anti-HER2 therapy.
IV. To characterize patterns and frequency of disease recurrence in participants stopping anti-HER2 therapy by length of time on anti-HER2 therapy.
V. To describe the proportion of participants choosing to stop or continue anti-HER2 therapy while both Cohorts 1 and 2 are open.
EXPLORATORY CORRELATIVE OBJECTIVES:
I. To explore minimal residual disease (MRD) status before and throughout the study period as a predictor of durable response.
Ia. The proportion of participants who are MRD-positive at baseline;
Ib. The relationship between serial MRD status and clinical outcomes (PFS, OS).
II. To characterize the mutational profile via circulating tumor deoxyribonucleic acid (DNA) (ctDNA) in participants who develop progression of disease.
III. To explore blood biomarkers of antitumoral immune activity as predictors of durable response or progression.
PATIENT-REPORTED OUTCOMES OBJECTIVES:
I. To evaluate change in illness intrusiveness in exceptional responders with HER2-positive MBC who stop anti-HER2 therapy.
II. To evaluate financial toxicity in exceptional responders with HER2-positive MBC who stop anti-HER2 therapy.
III. To describe anxiety in exceptional responders with HER2-positive MBC who stop anti-HER2 therapy.
IV. To describe symptoms, anxiety and quality of life (QOL) in exceptional responders with HER2-positive MBC who do and do not stop anti-HER2 therapy.
V. To describe decision regret in exceptional responders with HER2-positive MBC who stop anti-HER2 therapy.
VI. To describe distress about cancer progression in exceptional responders with HER2-positive MBC who do and do not stop anti-HER2 therapy.
VII. To describe illness intrusiveness in exceptional responders with HER2-positive MBC who continue anti-HER2 therapy.
VIII. To describe financial toxicity in exceptional responders with HER2-positive MBC who continue anti-HER2 therapy.
IX. To describe factors that impact exceptional responders' decisions to stop or continue anti-HER2 therapy.
X. To describe participants' perceptions about the risk of progression of HER2-positive MBC in the setting of continued treatment or a treatment break and about the success of resumption of anti-HER2 therapy following a treatment break.
XI. To describe exceptional responders' perceptions regarding their providers' preferences about stopping or continuing anti-HER therapy.
OUTLINE: Patients who choose to continue anti-HER2 therapy are assigned to Cohort 1, while patients who choose to discontinue anti-HER2 therapy are assigned to Cohort 2.
COHORT 1: Patients continue receiving anti-HER2 therapy on study as per standard of care. Patients also undergo collection of blood samples on study and during follow up, and undergo computed tomography (CT) or positron emission tomography (PET) scans throughout the trial. Patients with stable brain metastases also undergo magnetic resonance imaging (MRI) scans throughout the trial.
COHORT 2: Patients discontinue anti-HER2 therapy and undergo surveillance on study. Patients experiencing disease progression while on surveillance may re-initiate anti-HER2 therapy as clinically indicated. Patients who re-initiate anti-HER2 therapy may undergo an optional tumor tissue biopsy on study. Patients also undergo collection of blood samples on study and during follow up, and undergo CT or PET scans throughout the trial. Patients with stable brain metastases also undergo MRI scans throughout the trial.
Patients may be followed every 6 months regardless of disease status for a minimum of 3 years and up to 10 years, or until death, whichever occurs first.
