Impact of Omitting Chemo Based on Patient's Selection for ER-Positive, HER2-Negative Breast Cancer With Ribociclib and Endocrine Therapy

Eligibility Criteria

• 1. Female or male age ≥ 18 years old and have the ability to understand and the willingness to sign a written informed consent document.
• 2. Participants may have ipsilateral or contralateral synchronous breast cancer if the highest stage tumor meets entry criteria, and the other sites of disease would not require chemotherapy or HER2-directed therapy.
• 3. Participants may have multicentric or multifocal breast cancer if the highest stage tumor meets entry criteria, and the other sites of disease would not require chemotherapy or HER2-directed therapy.
• 4. Participants underwent a total mastectomy, skin-sparing mastectomy, nipple-sparing mastectomy, or a lumpectomy.
• 5. For participants who undergo a lumpectomy, the margins of the resected specimen or re-excision must be histologically free of invasive tumor and DCIS with no ink on tumor as determined by the local pathologist. If pathologic examination demonstrates tumor at the line of resection, additional excisions may be performed to obtain clear margins.
• 6. For participants who undergo mastectomy, the margins must be free of residual gross tumor.
• 7. Participants must have undergone axillary staging with sentinel node biopsy (SNB), targeted axillary dissection (TAD), or axillary lymph node dissection (ALND).
• 8. The following staging criteria must be met postoperatively according to AJCC 8th edition criteria: Men or premenopausal women with T1-3N1-2. Postmenopausal women with T3N1 or T1-3N2 diseases.
• 9. The tumor must be ER-positive (≥ 10%), HER2-negative, by current ASCO/CAP guidelines based on testing results. HER2-negative breast cancer is defined as a negative in situ hybridization test or an immunohistochemistry (IHC) status of 0 or 1+. If IHC is 2+, a negative in situ hybridization (FISH, CISH, or SISH) test is required to confirm the participant's HER2-negative status (based on the most recently analyzed tissue sample tested by a local laboratory).
• 10. Oncotype Dx Recurrence Score must be 0 - 25.
• 11. Participants with known menopausal status at the time of screen.
• 12. The interval between the last surgery for breast cancer (including re-excision of margins) and screening must be no more than 16 weeks.
• 13. HIV-infected participants with undetectable viral load within 6 months and in long term anti-retroviral therapy that would not have a significant drug-drug interaction with ribociclib are eligible for this trial.
• 14. Radiation therapy should be used according to standard guidelines.
• 15. Participants must have an ECOG performance status of 0 to 1 within 28 days prior to initiation of the study treatment.
• 16. Participant is able to swallow oral medications.
• 17. Participants must have adequate organ and marrow function as defined below. All laboratory values must be obtained within 14 days prior to screening.
• 1. Absolute neutrophil count (ANC) ≥ 1.5 × 109/L.
• 2. Platelets ≥ 100 × 109/L.
• 3. Hemoglobin ≥ 9.0 g/dL.
• 4. Estimated glomerular filtration rate (eGFR) ≥ 30 mL/min/1.73m2 according to the Modification of Diet in Renal Disease (MDRD) formula.
• 5. Alanine transaminase (ALT) \< 2.5 × Upper Limit Normal (ULN).
• 6. Aspartate transaminase (AST) \< 2.5 × ULN.
• 7. Total serum bilirubin \< ULN; or total bilirubin ≤ 3.0 × ULN or direct bilirubin ≤ 1.5 × ULN in patients with well documented Gilbert's Syndrome.
• 8. International normalized ratio (INR) ≤ 1.5 (unless the patient is receiving anticoagulants, and the INR is within the therapeutic range of intended use for that anticoagulant within 7 days prior to enrollment).
• 9. Patient must have the following laboratory values within normal limits or corrected to within normal limits with supplements (the local laboratory value should be documented within normal limits after the correction) before enrollment:
• * Potassium.
• * Magnesium.
• * Total Calcium (corrected for serum albumin).
• 18. Standard 12-lead ECG values assessed as: QTcF interval (using Fridericia's correction) at screening \< 450 msec. Resting heart rate 50-90 beats per minute (determined from the ECG).
• 19. Participant must be willing and able to comply with scheduled visits, treatment plans, laboratory tests, and other trial procedures.
• 20. Participants must adhere to the following reproductive and contraceptive requirements while on study treatment and for the specified duration after the last dose of the treatment drugs.
• 21. Participant has no contraindication for the adjuvant ET in the trial and is planned to be treated with ET for five years or more.
• 1. Definitive clinical or radiologic evidence of distant metastases of breast cancer beyond regional lymph nodes (stage IV according to AJCC 8th edition) and/or evidence of recurrence after curative surgery.
• 2. T4 tumors, including inflammatory breast cancer.
• 3. N3 tumors.
• 4. Participants that have received neoadjuvant chemotherapy or biotherapy.
• 5. Participant has received prior treatment with tamoxifen, raloxifene or AIs for reduction in risk ("chemoprevention") of breast cancer and/or treatment for osteoporosis within the last two years prior to randomization. Participant is concurrently using hormone replacement therapy.
• 6. Participants with a known hypersensitivity to any of the excipients of ribociclib and/or ET (e.g. rare hereditary problems of galactose intolerance, the Lapp lactase deficiency, glucose-galactose malabsorption, and soy allergy).
• 7. History of ipsilateral or contralateral invasive breast cancer: Participants with synchronous and/or previous ductal carcinoma in situ (DCIS) or lobular carcinoma in situ (LCIS) are eligible. If prior ipsilateral DCIS was treated with lumpectomy and radiation therapy, a mastectomy must have been performed for the current cancer.
• 8. Participant has received any CDK4/6 inhibitor.
• 9. Participant has a concurrent invasive malignancy or a prior invasive malignancy whose treatment was completed within two years before randomization. Note: Participants with adequately treated basal or squamous cell skin carcinoma or curatively resected cervical cancer in situ are eligible.
• 10. Participant has known active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection (testing is not mandatory, unless required by local regulation).
• 11. Life expectancy of \<10 years due to co-morbid conditions in the opinion of the treating investigator.
• 12. Non-epithelial breast malignancies such as sarcoma or lymphoma.
• 13. Hormonally based contraceptive measures must be discontinued prior to registration (including progestin/progesterone IUDs).
• 14. Pregnancy or lactating women or women who plan to become pregnant or breast-feed during the trial.
• 15. Clinically significant, uncontrolled heart disease and/or cardiac repolarization abnormality, including any of the following:
• 1. History of documented myocardial infarction (MI), angina pectoris, symptomatic pericarditis, or coronary artery bypass graft within six months prior to screening
• 2. Documented cardiomyopathy
• 3. Left Ventricular Ejection Fraction (LVEF) \< 50% as determined by Multiple Gated acquisition (MUGA) scan or echocardiogram (ECHO) within six months prior to screening.
• 4. Long QT syndrome or family history of idiopathic sudden death or congenital long QT syndrome, or any of the following:
• 16. Participant is currently receiving any of the following substances within 7 days before registration:
• 1. Concomitant medications, herbal supplements, and/or fruits (e.g. grapefruit, pummelos, starfruit, Seville oranges) and their juices that are known as strong inhibitors or inducers of CYP3A4/5.
• 2. Medications that have a narrow therapeutic window and are predominantly metabolized through CYP3A4/5.
• 17. Participant is currently receiving or has received systemic corticosteroids ≤ 2 weeks prior to starting trial treatment or has not fully recovered from side effects of such treatment.
• 18. Participant has impairment of GI function or GI disease that may significantly alter the absorption of the oral trial treatments (e.g. uncontrolled ulcerative diseases, uncontrolled nausea, vomiting or diarrhea, malabsorption syndrome, or small bowel resection).
• 19. Participant has any other concurrent severe and/or uncontrolled medical condition that would, in the principal investigator's judgment, cause unacceptable safety risks, contraindicate patient participation in the clinical trial or compromise compliance with the protocol (e.g. chronic pancreatitis, chronic active hepatitis, liver cirrhosis or any other significant liver disease, active untreated or uncontrolled fungal, bacterial or viral infections, active infection requiring systemic anti-bacterial therapy, etc.) or limit life expectancy to ≤5 years.
• 20. Participation in other studies involving investigational drug(s) within 30 days prior to registration or within 5 half-lives of the investigational drug(s) (whichever is longer), or participation in any other type of medical research judged not to be scientifically or medically compatible with this trial. If the participant is enrolled or planned to be enrolled in another study that does not involve an investigational drug, the agreement of the Sponsor-Investigator is required to establish eligibility.