after joining the study you will be randomly placed in one of two groups. one group receives bgb-43395 plus letrozole; the other group receives a CDK4/6 inhibitor (abemaciclib, palbociclib or ribociclib) plus letrozole. the assignment is made by the study team and you will be informed which medicines you will take.

before starting medication you will have a physical check‑up, blood tests, and imaging scans (such as ct or mri) to record the current status of the cancer. these results are used as a reference for later comparisons.

if you are in the bgb-43395 plus letrozole group, you will take letrozole 2.5 mg by mouth once each day and bgb-43395 at the dose prescribed by the investigator, also taken by mouth once each day.

if you are in the CDK4/6 inhibitor plus letrozole group, you will take letrozole 2.5 mg by mouth once each day and one of the following:

abemaciclib 300 mg by mouth once each day,

palbociclib 125 mg by mouth once each day for three weeks followed by one week without the drug (a 28‑day cycle),

ribociclib 600 mg by mouth once each day for three weeks followed by one week without the drug (a 28‑day cycle).

you will visit the clinic roughly every four weeks. during these visits blood tests and a review of any side effects will be performed to ensure the medication is tolerated.

imaging scans to evaluate the tumor will be done about every eight weeks. the scans are compared with the baseline images to determine whether the disease is stable, improving, or progressing.

you will keep taking the assigned medicines daily (or according to the 3‑weeks‑on, 1‑week‑off schedule for palbociclib or ribociclib) until one of the following occurs:

the cancer shows progression on imaging,

unacceptable side effects develop,

the investigator decides to stop treatment for any reason,

or the study reaches its planned end.

when treatment stops, a final set of assessments will be performed, including physical exam, blood tests, and imaging, to record the condition of the disease at the time of discontinuation.