Hormonal Therapy after Pertuzumab and Trastuzumab for the Treatment of Hormone Receptor Positive, HER2 Positive Breast Cancer, the ADEPT study

Summary

Objectives

PRIMARY OBJECTIVE:
I. To evaluate 3-year invasive disease-free survival (iDFS) in patients with stage I hormone receptor positive (HR+) HER2+ breast cancer treated with adjuvant hyaluronidase-zzxf/pertuzumab/trastuzumab (HP) plus endocrine therapy.

SECONDARY OBJECTIVES:
I. To evaluate iDFS at 7 and 10 years in patients with stage I HR+ HER2+ breast cancer treated with adjuvant HP plus endocrine therapy, in:
Ia. All patients.
Ib. Patient subgroups according to intrinsic subtype (HER2-enriched, luminal, basal).
II. To evaluate recurrence-free interval (RFI) at 3, 7, and 10 years in patients with stage I HR+ HER2+ breast cancer treated with adjuvant HP plus endocrine therapy, in:
IIa. All patients.
IIb. Patient subgroups according to intrinsic subtype (HER2-enriched, luminal, basal).
III. To evaluate breast cancer-specific survival (BCSS) at 3, 7, and 10 years in patients with stage I HR+ HER2+ breast cancer treated with adjuvant HP plus endocrine therapy, in:
IIIa. All patients.
IIIb. Patient subgroups according to intrinsic subtype (HER2-enriched, luminal, basal).
IV. To evaluate overall survival (OS) at 3, 7, and 10 years in patients with stage I HR+ HER2+ breast cancer treated with adjuvant HP plus endocrine therapy, in:
IVa. All patients
IVb. Patient subgroups according to intrinsic subtype (HER2-enriched, luminal, basal)
V. To assess safety and tolerability of one year of subcutaneous HP plus endocrine therapy.
VI. To estimate the mean difference in total patient chair time of drug administration and observation, comparing treatment with HP fixed dose combination (FDC) subcutaneously (SC) and treatment with intravenous (IV) administration of HP as part of the Time and Motion substudy.

EXPLORATORY AND CORRELATIVE OBJECTIVES:
I. To evaluate quality of life, patient satisfaction, financial concerns, patient acceptance of subcutaneous administration at home, and hormonal therapy adherence over time in patients treated with HP plus endocrine therapy.
II. To explore how the presence, absence, and characteristics (i.e. presence of certain mutations) of detectable circulating tumor deoxyribonucleic acid (DNA) correlates with long-term outcomes (iDFS, RFI, OS) on HP plus hormonal therapy.
III. To explore how features of the pre-treatment immune microenvironment correlate with long-term outcomes (iDFS, RFI, OS) on HP plus hormonal therapy.
IV. To estimate the mean difference in overall patient treatment experience time (comparing FDC HP to IV HP) as part of the Time and Motion substudy.
V. To estimate the mean difference (comparing FDC HP to IV HP) in drug administration time, as part of the Time and Motion substudy.
VI. To estimate the mean difference (comparing FDC HP to IV HP) in pharmacist time commitment for drug preparation, as part of the Time and Motion substudy.

OUTLINE:
Patients receive HP SC over 5-8 minutes on day 1. Treatment repeats every 21 days for up to 18 cycles in the absence of disease progression or unacceptable toxicity. Postmenopausal women also receive either letrozole orally (PO) once daily (QD), anastrozole PO QD, or exemestane PO QD, and pre- and postmenopausal women and men receive tamoxifen PO QD on days 1-21. Treatment repeats every 21 days for at least 5 years in the absence of disease progression or unacceptable toxicity. Premenopausal or male patients may receive gonadotropin-releasing hormone analog intramuscularly (IM) once monthly or every 3 months for at least 5 years in the absence of disease progression or unacceptable toxicity. NOTE: Patients able to tolerate SC trastuzumab but unable to tolerate SC pertuzumab may receive trastuzumab/hyaluronidase-oysk SC together with pertuzumab intravenously (IV). Patients unable to tolerate SC trastuzumab may receive IV trastuzumab.

TIME AND MOTION SUB-STUDY: Patients receive HP SC over 5-8 minutes on day 1 in cycles 1 and 4-18, and pertuzumab IV and trastuzumab IV in cycles 2-3. Treatment repeats every 21 days for up to 18 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up annually until 10 years after trial registration.