IMPlementing geriatric assessment for dose Optimization of CDK 4/6-inhibitors in older bReasT cAncer patieNTs – a pragmatic randomized-controlled trial (IMPORTANT trial)

Prior treatment

• Patients considered from treating physician as non-suitable for treatment with CDK 4/6-inhibitors.

Other illness

• Contraindications according to SmPC for the CDK 4/6-inhibitors that is planned to be used.Specifically, any hypersensitivity to the active substance or to any of the excipients or to peanut, soya (for ribociclib) or use of preparations containing St. John’s Wort (for palbociclib) are contraindications.
• History of any other cancer (except of non-melanoma skin cancer or carcinoma in-situ of the cervix), unless in complete remission with no therapy for a minimum of 3 years.
• Patients with cognitive impairment (as assessed by treating physician) that preclude the ability to fill out the self-reported CGA.

Other

• Presence of visceral crisis, lymphangitis carcinomatosis, or leptomeningeal carcinomatosis.
• Participating in other interventional trial.

• Patients male or female aged at least 65 years old at the time of informed consent. Male patients should use adequate contraceptive methods (e.g., double-barrier contraception) during therapy and for at least 14 weeks after completing therapy.
• Able to understand and consent in English language or in native language for each participating country.
• Histologically or cytologically confirmed diagnosis of HR-positive (defined as estrogen-receptor ≥ 1%), HER2-negative breast cancer according to analysis of the most recent tumor specimen by local laboratory.
• Advanced (locoregionally recurrent or metastatic) breast cancer not amenable to curative treatment.
• No prior systemic treatment for advanced disease (recurrence during neo-/adjuvant endocrine therapy is allowed). A prior period of treatment with aromatase inhibitors or fulvestrant for up to 56 days from the CDK 4/6-inhibitor initiation is allowed as long as there is no disease progression during this time period.
• Adjuvant treatment with CDK4/6-inhibitors is allowed provided a disease-free interval from treatment end >12 months
• Written informed consent prior to any study-specific procedures.
• Adequate organ function as defined in the summary of product characteristics (SmPC) for the CDK 4/6-inhibitors that is planned to be used including ECG for assessment of QT interval before treatment with ribociclib. Specifically, the following thresholds should be used to define adequate organ function: absolute neutrophil counts of ≥ 1,000/mm3, platelet counts of ≥ 100,000/mm3; ALT and/or AST ≤ 3 x upper limit normal (ULN), total bilirubin ≤ 2 x ULN; eGFR ≥ 30 mL/min.
• Able to swallow capsules.