• Federation of Gynecology and Obstetrics (FIGO) 2009 stage IA-IVB, non-recurrent, chemotherapy (chemo)-naive, HER2-positive endometrial serous carcinoma or endometrial carcinosarcoma
• Histologic confirmation of the original primary tumor is required. Submission of surgical pathology report (or endometrial biopsy pathology report in patients who never undergo hysterectomy) is required
• Patients must be within 8 weeks of primary surgery (or endometrial biopsy in patients who never undergo hysterectomy) at the time of study registration
• Patients may have measurable disease, non-measurable disease, or no measurable disease. In patients with measurable disease, lesions will be defined and monitored by RECIST v 1.1. Measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded). Each lesion must be >= 10 mm when measured by computed tomography (CT) or magnetic resonance imaging (MRI). Lymph nodes must be >= 15 mm in short axis when measured by CT or MRI
• For patients with uterine-confined (stage I) disease, the tumor must be invasive into the myometrium. Any amount of myoinvasion is acceptable for eligibility. Patients with non-invasive disease, endometrial intraepithelial carcinoma alone, or disease confined to a polyp will be excluded
• All patients must have tumors that are HER2 positive as defined by American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) 2018 Breast Cancer guidelines (https://documents.cap.org/documents/algorithim-evaluation-her2.pdf. In general HER2 positivity is defined as any of the following:
  • 3+ immunohistochemistry (IHC),
  • 2+ IHC with positive in situ hybridization (ISH)
  • Average HER2 copy number >= 6.0 signals/cell
  • Average HER2 copy number >= 4.0 and < 6.0 signals/cell, with concurrent IHC 3+
  • HER2/CEP17 ratio >= 4.0 signals/cell
  • HER2/CEP 17 ratio >= 2.0 and < 4.0, with concurrent IHC 3+ IHC and ISH testing will be done locally, at each participating institution and interpreted by local pathologists. Alternatively, patients could be eligible if next generation sequencing (NGS) demonstrates HER2 (ERBB2) amplification. NGS testing can be performed through any designated labs as per the National Cancer Institute (NCI) MATCH/NCI Combo-MATCH trial (https://ecog-acrin.org/nci-match-eay131-designated-labs).

        Pathology report showing results of institutional HER2 testing (or NGS testing results)
        must be submitted.
        Sites must submit all results available (IHC, ISH, and NGS)
          -  Additionally, patients must have the following histologic types to be eligible:
               -  Serous adenocarcinoma (may include =< 10% non-serous histology)
               -  Carcinosarcoma with serous epithelial component (only the serous component needs
                  to be HER2 positive; may include =< 10% non-serous histology)
               -  In cases where determination of serous is equivocal or challenging, aberrant p53
                  immunohistochemistry (IHC) (defined as overexpression of p53 compared to internal
                  controls) will be sufficient for inclusion
          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2
          -  Age >= 18
          -  Platelets >= 100,000/mcl (within 14 days prior to registration)
          -  Absolute neutrophil count (ANC) >= 1,500/mcl (within 14 days prior to registration)
          -  Creatinine =< 1.5 x institutional/laboratory upper limit of normal (ULN) or estimated
             Glomerular filtration rate (eGFR) >= 50 mL/min using either the Cockcroft-Gault
             equation, the Modification of Diet in Renal Disease Study, or as reported in the
             comprehensive metabolic panel/basic metabolic panel (eGFR). (within 14 days prior to
             registration)
          -  Total serum bilirubin level =< 1.5 x ULN (patients with known Gilbert's disease who
             have bilirubin level =< 3 x ULN may be enrolled) (within 14 days prior to
             registration)
          -  Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 3 x ULN (within
             14 days prior to registration)
          -  Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral
             therapy with undetectable viral load within 6 months of registration are eligible for
             this trial
          -  Although the uterus will have been removed in the vast majority of patients, for
             patients of child-bearing potential: negative urine or serum pregnancy test. If the
             urine test is positive or cannot be confirmed as negative, a serum pregnancy test is
             required. Patients will be considered of non-reproductive potential if they are
             either:
               -  Postmenopausal (defined as at least 12 months with no menses without an
                  alternative medical cause; in women < 45 years of age, a high follicle
                  stimulating hormone [FSH] level in the postmenopausal range may be used to
                  confirm a postmenopausal state in women not using hormonal contraception or
                  hormonal replacement therapy. In the absence of 12 months of amenorrhea, a single
                  FSH measurement is insufficient); OR
               -  Have had a hysterectomy and/or bilateral oophorectomy, bilateral salpingectomy or
                  bilateral tubal ligation/occlusion at least 6 weeks prior to registration
               -  Have a congenital or acquired condition that prevents childbearing
          -  Patients with a prior or concurrent malignancy whose natural history or treatment does
             not have the potential to interfere with the safety or efficacy assessment of the
             investigational regimen are eligible for this trial.
          -  Patients with evidence of chronic hepatitis B virus (HBV) infection must have an
             undetectable HBV viral load on suppressive therapy, if indicated
          -  Patients with a history of hepatitis C virus (HCV) infection must have been treated
             and cured. For patients with HCV infection who are currently on treatment, they are
             eligible if they have an undetectable HCV viral load
          -  Patients with treated brain metastases are eligible if follow-up brain imaging after
             central nervous system (CNS)-directed therapy shows no evidence of progression
          -  The patient or a legally authorized representative must provide study-specific
             informed consent prior to study entry and, for patients treated in the United States
             (U.S.), authorization permitting release of personal health information
        Exclusion Criteria:
          -  Prior Therapy:
               -  Patients must NOT have received prior chemotherapy, biologic therapy, or targeted
                  therapy for treatment of endometrial carcinoma
               -  Patients must NOT have received prior radiation therapy for treatment of
                  endometrial carcinoma. Prior radiation includes external beam pelvic radiation
                  therapy, external beam extended field pelvic/para-aortic radiation therapy,
                  and/or intravaginal brachytherapy
                    -  NOTE: Vaginal brachytherapy for treatment of endometrial cancer is permitted
                       during study treatment. Planned use of vaginal brachytherapy must be
                       declared at time of registration
               -  Patients may have received prior hormonal therapy for treatment of endometrial
                  carcinoma. All hormonal therapy must be discontinued at least one week prior to
                  registration
          -  Patients may not have a planned interval cytoreduction or hysterectomy, prior to
             documentation of progression, after study registration
          -  Patients may not have planned external beam radiotherapy, prior to documentation of
             progression, after study registration
          -  Significant cardiovascular disease including:
               -  Uncontrolled hypertension, defined as systolic > 150 mm Hg or diastolic > 90 mm
                  Hg despite antihypertensive medications
               -  Myocardial infarction or unstable angina within 6 months prior to registration
               -  New York Heart Association functional classification II, III or IV
               -  Serious cardiac arrhythmia requiring medication. This does not include
                  asymptomatic, atrial fibrillation with controlled ventricular rate
          -  Significant lung disease: dyspnea at rest grade 2 or greater (resulting from extensive
             tumor involvement or other causes), pneumonitis grade 2 or greater, interstitial lung
             disease grade 2 or greater, idiopathic pulmonary fibrosis, cystic fibrosis,
             Aspergillosis, active tuberculosis, or history of opportunistic infections
             (pneumocystis pneumonia or cytomegalovirus pneumonia)
          -  Patients with uncontrolled intercurrent illness including, but not limited to: ongoing
             or active infection (except for uncomplicated urinary tract infection), uncontrolled
             interstitial lung disease, symptomatic congestive heart failure, or psychiatric
             illness/social situations that would limit compliance with study requirements
          -  Treatment with strong CYP2C8 or CYP3A4 inhibitors or inducers within 14 days or 5
             drug-elimination half-lives, whichever is longer, prior to registration
          -  Women who are unwilling to discontinue nursing