T-DM1 With or Without Abemaciclib for the Treatment of HER2-Positive Metastatic Breast Cancer

Inclusion Criteria

• •Agree to undergo a core biopsy of breast cancer tissue derived from a local, regional or distant site for mandatory confirmation of ER+/ER-, progesterone receptor (PR) and HER2 status
• •* NOTE: If a single lesion is present, imaging must be completed after the lesion is biopsied and measurements must be taken from this image for disease evaluation by Response Evaluation Criteria in Solid Tumors (RECIST) to be considered eligible for this trial
• •* NOTE: The study requires a fresh biopsy for clinical and research purposes and archival tissue does not suffice. If the patient has already undergone a biopsy at the time of disease progression prior to enrolling on the trial, an additional research biopsy will still be required
• •Imaging or histologic evidence of progression of unresectable locally advanced or metastatic breast cancer
• •One of the following must be true:
• •* Progressed/relapsed during or within 12 months of completing neo-adjuvant treatment with a regimen containing a taxane, trastuzumab and pertuzumab
• •* Progressed/relapsed during or within 12 months of completing adjuvant treatment with a regimen containing a taxane, trastuzumab and pertuzumab
• •* Progressed/relapsed during metastatic treatment with a regimen containing a taxane, trastuzumab and pertuzumab
• •* Progressed/relapsed \> 12 months after receipt of adjuvant T-DM1
• •A total of 1 or 2 prior lines of the following breast cancer therapies in any disease setting
• •* Chemotherapy alone
• •* HER2-directed therapy alone
• •* Chemotherapy with HER2 directed therapy
• •* Note: Any number of prior lines of endocrine therapy received in any disease setting
• •Measurable disease as defined by RECIST criteria
• •Local, histological confirmation of metastatic HER2-positive breast cancer per American Society of Clinical Oncology (ASCO) College of American Pathologists (CAP) guidelines; one of the following must apply
• •* 3+ by immunohistochemistry (IHC)
• •* 2+ by IHC and in situ hybridization (ISH) amplified
• •Discontinued all cancer therapies (chemotherapy, radiotherapy, immunotherapy, and endocrine therapy), except trastuzumab, \>= 21 days prior to randomization for myelosuppressive agents or \>= 14 days prior to randomization for non-myelosuppressive agents
• •* NOTE: All residual toxicities (except alopecia) should be at baseline or grade 1 (including peripheral neuropathy)
• •* NOTE: If indicated, patients can commence treatment with bisphosphonates of RANK-L inhibitors (e.g., denosumab) any time prior to randomization. No washout period or treatment delay is required prior to commencing study treatment
• •Absolute neutrophil count \>= 1.5 x 10\^9/L (obtained =\< 14 days prior to randomization)
• •Platelet count \>= 100,000/mm\^3 (obtained =\< 14 days prior to randomization)
• •Hemoglobin \>= 9.0 g/dL (obtained =\< 14 days prior to randomization)
• •Creatinine =\< 1.5 X upper limit of normal (ULN) (obtained =\< 14 days prior to randomization)
• •Total bilirubin =\< 1.5 x ULN (obtained =\< 14 days prior to randomization) (except in cases of known Gilbert's syndrome where =\< 2.0 x ULN is allowed and direct bilirubin within normal levels is permitted)
• •Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =\< 2.5 x ULN (obtained =\< 14 days prior to randomization)
• •* NOTE: If liver metastases are present, AST and ALT =\< 5 x ULN are acceptable
• •Prothrombin time (PT)/international normalized ratio (INR)/partial thromboplastin time (PTT) =\< 1.5 X ULN OR if patient is receiving anticoagulant therapy and PT or PTT is within therapeutic range of intended use of coagulants (obtained =\< 14 days prior to randomization)
• •Negative pregnancy test =\< 7 days prior to randomization, for persons of childbearing potential only
• •* NOTE: A female of childbearing potential must have a negative serum pregnancy test within 7 days of the first dose of T-DM1 +/- abemaciclib and agree to use a highly effective contraception method during the treatment period and for 6 months following the last dose of T-DM1 +/- abemaciclib
• •* Women and men of reproductive potential should agree to use an appropriate method of birth control throughout their participation in this study due to the teratogenic potential of the therapy utilized in this trial. Appropriate methods of birth control include abstinence, oral contraceptives, implantable hormonal contraceptives or double barrier method (diaphragm plus condom). Birth control must be used during the treatment period and continued for at least 6 months after the last dose of treatment with T-DM1 +/- abemaciclib
• •* Cases of pregnancy that occur during maternal exposures to T-DM1+/- abemaciclib, or cases of pregnancy in female partners/spouses of male patients, should be reported. If a female patient is determined to be pregnant following T-DM1 +/- abemaciclib initiation, she must discontinue treatment immediately. Data on fetal outcome and breast-feeding are to be collected for regulatory reporting and drug safety evaluation
• •Willingness to provide mandatory blood specimens for correlative research