Discontinuation of CDK4/6 Inhibitors in Patients With Metastatic HR Positive, HER2 Negative Breast Cancer

Inclusion Criteria:

1. Female patient has given written informed consent

2. Patient is ≥ 18 years of age at time of signing the written informed consent

3. Patient has been diagnosed with histologically confirmed metastatic adenocarcinomaof the breast

4. Patient has documented histological or cytological confirmation of estrogen receptorpositive (ER+) and HER2 negative (HER2-) disease

5. Patient has no curative treatment option by surgery or radiotherapy

6. Patient was treated with CDK4/6 inhibitor plus endocrine therapy for at least 12months with disease control (complete remission, partial remission or stabledisease) as judged by the treating physician before planned study treatmentinitiation

7. Patient has a preserved performance status (ECOG ≤ 2)

8. Patient has adequate bone marrow, renal and hepatic function:

9. Hemoglobin > 9.0 g/dL

10. Absolute neutrophil count judged as appropriate for study therapy by theinvestigator

11. Platelets ≥ 100 x 109/L

12. Calculated creatinine clearance judged as appropriate for study therapy by theinvestigator

13. AST (SGOT) / ALT (SGPT) and alkaline phosphatase ≤ 2.5x ULN

14. Serum albumin > 30 g/L

15. Patients considered postmenopausal according to one of the following definition:

16. Women <50 years of age who are amenorrheic for 12 months or more followingcessation of exogenous hormonal treatments and whose levels of luteinizinghormone and follicle-stimulating hormone are in the post-menopausalinstitutional range

17. Women ≥50 years of age who are amenorrheic for 12 months or more followingcessation of all exogenous hormonal treatments, had radiation-induced menopausewith last menses >1 year ago or had chemotherapy-induced menopause with lastmenses >1 year ago

18. Artificially induced postmenopausal women (by Gonadotropin-releasing hormone [GnRH] analogs)

19. WOCBP must have a negative serum pregnancy test within 7 days prior to start oftrial

Exclusion Criteria:

1. Patient has active (or history of) brain or leptomeningeal metastases

2. Patient is pre- or perimenopausal. Patient is pregnant or breast feeding or planningto become pregnant within five times the half-life of the IMPs after the end oftreatment.

3. Patient has significant cardiovascular disease, such as cardiac disease (New YorkHeart Association Class II or greater), myocardial infarction or cerebrovascularaccident within 6 months prior to initiation of study treatment, unstablearrhythmias, or unstable angina

4. Patient has other concomitant or previous malignancy, except adequately treatedin-situ carcinoma of the uterine cervix, basal or squamous cell carcinoma of theskin, cancer in complete remission for > 5 years

5. Patient has contraindication or shows hypersensitivity to the existing treatmentwith CDK4/6 inhibitor plus endocrine therapy

6. Patient shows evidence of any other disease, neurologic or metabolic dysfunction,physical examination finding or laboratory finding giving reasonable suspicion of adisease or condition that contraindicates the use of any of the study medications,puts the patient at higher risk for treatment-related complications or may affectthe interpretation of study results

7. Patient participated in another clinical study with an investigational medicinalproduct during the last 28 days before treatment initiation or 7 half-lives ofpreviously used trial medication, whichever is longer or participate in such a studyat the same time as this trial. Note: Participation in non-interventional clinical studies or registries is allowed.

8. Any co-existing medical condition that in the investigator's judgement willsubstantially increase the risk associated with the patient's participation in thestudy.

9. Patient who has been incarcerated or involuntarily institutionalized by court orderor by the authorities.

10. Patients who are unable to consent because they do not understand the nature,significance and implications of the clinical trial and therefore cannot form arational intention in the light of the facts.