This phase III trial compares 6 months of human epidermal growth factor receptor 2 (HER2)-targeted therapy to 12 months of HER2-targeted therapy for the treatment of HER2-positive (+) breast cancer in patients that had a pathologic complete response (pCR) after preoperative (neoadjuvant) chemotherapy with trastuzumab. Trastuzumab and pertuzumab are monoclonal antibodies and forms of targeted therapy that attach to a receptor protein called HER2. HER2 is found on some cancer cells. When trastuzumab or pertuzumab attach to HER2, the signals that tell the cells to grow are blocked and the tumor cell may be marked for destruction by the body's immune system. Giving 6 months of HER2-targeted therapy may work better than giving 12 months for the treatment of HER2+ breast cancer in patients that had a pCR after neoadjuvant chemotherapy with trastuzumab.
Patients (females and males) with clinical stage T1c-T3 (or Tx) and nodal stage N0-N1 (except T3N1 tumors, which are not eligible)
Patients must have no residual invasive disease in the breast or lymph nodes after the completion of neoadjuvant therapy. Residual ductal carcinoma in situ (DCIS) is allowed. Patients with residual isolated tumor cells at surgery are considered node-positive and are not eligible
HER2+ by American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines. Central pathology review is not required. In cases where there were multiple tumor sites in breast/nodes that had HER2 testing at diagnosis, at least one site must have been HER2+ AND the treating investigator must feel it is in the patient's best interest to be treated as having HER2+ breast cancer
Known hormone receptor status as defined by ASCO/CAP guidelines. Estrogen receptor (ER) and progesterone receptor (PR) of any values are allowed. Hormone receptor positive status can be determined by either known positive ER or known positive PR status; hormone receptor negative status must be determined by both known negative ER and known negative PR
None
Parallel
Trastuzumab (Herceptin)
Biological/VaccineGiven IV or SC
Pertuzumab
Biological/VaccineGiven IV or SC
Echocardiography
Procedure/SurgeryUndergo ECHO
Multigated Acquisition Scan
Procedure/SurgeryUndergo MUGA
Mammography
Procedure/SurgeryUndergo mammography
Ultrasound
Procedure/SurgeryUndergo ultrasound
Magnetic Resonance Imaging
Procedure/SurgeryUndergo MRI
Biospecimen Collection
Procedure/SurgeryUndergo blood and tissue sample collection
Questionnaire Administration
Other interventionAncillary studies
Recurrence-free survival (RFS)
The Kaplan-Meier method will be used to estimate the distribution of RFS times and a stratified log-rank test for non-inferiority will be used to assess whether RFS with 6 total months of human epidermal growth factor receptor 2 (HER2)-blockade is non-inferior to standard-of-care 12 total months of HER2-blockade in this patient population. Stratified Cox modeling will be used to estimate the hazard ratio and corresponding one-sided 95% confidence interval (CI).
Functional Assessment of Cancer Therapy-Breast (FACT-B) total score (Quality of life)
Will compare the FACT-B total score between patients randomized to receive 6 months versus 12 months of combined neoadjuvant/adjuvant HER2 blockade. All questionnaires will be scored according to published scoring algorithms, including recommendations for addressing missing items within a scale. An intention-to-treat (ITT) approach will be used for all analyses. All statistical tests will be 2-sided, and p-values \< 0.05 will be considered statistically significant. To evaluate the between-arm mean difference in scores, a repeated measures mixed model will be estimated based on FACT-B total scores at all time points.
Incidence of grade 3 or higher adverse events (AE)
Will be according to the Common Terminology Criteria for Adverse Events version 5.0. The maximum grade of a specific AE experienced by a patient will be used. The proportion of patients who report a grade 3 or higher AE will be compared between the two treatment arms with a chi-square test. AEs (type and grade) for both arms will be summarized with the frequency and relative frequency
Locoregional recurrence (LRR)
The cumulative incidence of LRR will be analyzed with Kaplan-Meier estimates (curve starting at 0 rather than 1) and compared with a stratified log rank test.
Overall survival
Will be compared between the treatment arms with a stratified log rank test and a stratified Cox model will be used to generate the hazard ratio estimate (both a point estimate and 95% CI). The analyses will be done as ITT groups as well as per-protocol groups.
RFS for key subgroups
Forest plots will be generated for key prognostic variables (including the stratification variables) and subgroups of interest to determine whether the treatment effect appears homogeneous across the subgroups for the ITT population. Additional key subgroups of interest are neoadjuvant chemotherapy backbone and the type of adjuvant HER2-blockade the patient actually received (dual versus single). With respect to the latter analysis, the interest will be in whether there is an apparent difference in treatment effect among patients who received adjuvant pertuzumab versus those who did not.
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Alliance for Clinical Trials in Oncology
Lead sponsor
National Cancer Institute (NCI)
Collaborator
