ShortStop-HER2: 12 months vs. 6 months of HER2-targeted Medications for People with HER2+ Breast Cancer who Had a Pathologic Complete Response after Chemotherapy Plus Trastuzumab

Summary

Objectives

PRIMARY OBJECTIVES:
I. To evaluate whether 6 months of combined neoadjuvant (neo)/adjuvant HER2 blockade results in a non-inferior recurrence-free survival (RFS) compared to 12 months of combined neo/adjuvant HER2 blockade, in patients with early stage HER2+ breast cancer who achieve pCR after neoadjuvant chemotherapy with HER2 blockade.
II. To compare the Functional Assessment of Cancer Therapy-Breast (FACT-B) total score at 12 months between patients randomized to receive 6 months versus 12 months of combined neo/adjuvant HER2 blockade. (Quality of life)

SECONDARY OBJECTIVES:
I. Secondary objectives are to evaluate whether 6 months compared to 12 months results in differences for the following:
Ia. Grade 3 or higher adverse event (AE) rates;
Ib. Overall survival (OS);
Ic. Locoregional recurrence (LRR, both isolated LRR as first events, and LRR events simultaneous with distant metastasis [DM]) incidence;
Id. RFS for key subgroups: baseline stage, hormone receptor (HR) status, neoadjuvant chemotherapy backbone, and dual versus single HER2 blockade in the adjuvant setting;
Ie. Time to central nervous system (CNS) recurrence (both isolated CNS recurrence as first events, and CNS recurrence events simultaneous with distant metastasis and/or LRR).
II. To compare the FACT-B total score at 18 months between patients randomized to receive 6 months versus 12 months of combined neo/adjuvant HER2 blockade. (Quality of life)
III. To compare side effect bother as measured by the Functional Assessment of Cancer Therapy General Population 5 (FACT GP5) item at 12 months between patients randomized to receive 6 months versus 12 months of combined neo/adjuvant HER2 blockade. (Quality of life)
IV. To compare specific patient-reported symptomatic adverse events (i.e. diarrhea, constipation, fatigue, and rash) as measured by the Patient Reported Outcomes-Common Terminology Criteria for Adverse Events (PRO-CTCAE) at 12 months between patients randomized to receive 6 months versus 12 months of combined neo/adjuvant HER2 blockade. (Quality of life)

QUALITY OF LIFE EXPLORATORY OBJECTIVES:
I. To examine the different FACT-B subscales at all other evaluable time points.
II. To examine heterogeneity of treatment effects within subgroups defined by subcutaneous versus intravenous treatment delivery.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM 1: Patients receive trastuzumab intravenously (IV) or trastuzumab/hyaluronidase-oysk subcutaneously (SC) on day 1 of each cycle. Patients may also receive pertuzumab IV or hyaluronidase-zzxf/pertuzumab/trastuzumab SC, at the discretion of the treating investigator, on day 1 of each cycle. Cycles repeat every 21 days for up to 17 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo echocardiography (ECHO) or multigated acquisition (MUGA) as well as mammography, ultrasound, or magnetic resonance imaging (MRI) throughout the trial. Patients may also optionally undergo blood and tissue sample collection throughout the trial.

ARM 2: Patients receive trastuzumab IV or trastuzumab/hyaluronidase-oysk SC on day 1 of each cycle. Patients may also receive pertuzumab IV or hyaluronidase-zzxf/pertuzumab/trastuzumab SC, at the discretion of the treating investigator, on day 1 of each cycle. Cycles repeat every 21 days for up to 9 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo ECHO or MUGA as well as mammography, ultrasound, or MRI throughout the trial. Patients may also optionally undergo blood and tissue sample collection throughout the trial.

After completion of study treatment, patients are followed up every 6 months for 5 years after registration or until recurrence and then annually for a total of 10 years after registration.