Combining CDK4/6 inhibitors with hormone therapy and what comes next for HR+/HER2- metastatic breast cancer

Observational Real-World Study on the Efficacy, Safety, and Biomarker Exploration of CDK4/6 Inhibitors Combined With Endocrine Therapy and Subsequent Treatment in HR+/HER2- Metastatic Breast Cancer.

This study will see how different follow-up treatments work after progression on CDK4/6 inhibitors plus hormone therapy in people with HR+/HER2- metastatic breast cancer.

Quick facts

• Study type: Observational
• Enrollment: 300 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Hunan Cancer Hospital (other)
• Drugs / interventions: radiation, chemotherapy
• Locations: 1 site (Changsha, Hunan)
• Trial ID: NCT06033287 on ClinicalTrials.gov

What this trial studies

This is a single-arm, non-interventional real-world study enrolling over 300 patients with HR+/HER2- metastatic or recurrent breast cancer who are receiving or planning to receive CDK4/6 inhibitors combined with endocrine therapy. Investigators will document the effectiveness and safety of the first-line CDK4/6 inhibitor plus endocrine therapy as given in routine practice. After disease progression, physicians will choose subsequent systemic treatments (for example switching CDK4/6 agents plus endocrine therapy, other endocrine regimens, chemotherapy, or targeted therapies), and outcomes and adverse events for those regimens will be recorded. The study aims to capture real-world sequencing decisions and outcomes to inform future practice.

Who should consider this trial

Good fit: Adults (≥18) with pathologically confirmed HR-positive/HER2-negative metastatic or recurrent breast cancer who are receiving or plan to receive first-line CDK4/6 inhibitor plus endocrine therapy and who can be treated and followed at Hunan Cancer Hospital are ideal candidates.

Not a fit: Patients with HER2-positive disease, those not treated with CDK4/6 inhibitors, those unable to attend the single study site, or those seeking an experimental intervention may not receive direct benefit from participation.

Why it matters

Potential benefit: If successful, the results could help doctors choose better follow-up treatments after progression, potentially improving disease control and avoiding unnecessary side effects.

How similar studies have performed: Randomized trials have demonstrated that CDK4/6 inhibitors improve outcomes in HR+/HER2- metastatic breast cancer, but evidence on the optimal sequencing of therapies after progression is limited and mainly comes from retrospective or small cohort studies.

Eligibility criteria

Inclusion Criteria:

* Inclusion criteria:

  * Age ≥ 18 years, postmenopausal or pre/perimenopausal females, or male patients. Female patients must meet one of the following criteria:

    1. Prior bilateral oophorectomy or age ≥ 60 years.
    2. Age \< 60 with natural postmenopausal status (defined as spontaneous cessation of regular menstruation for at least 12 consecutive months without any other pathological or physiological reasons), and estradiol (E2) and follicle-stimulating hormone (FSH) levels consistent with postmenopausal range.
    3. Pre/perimenopausal females may also be eligible but must be willing to receive LHRH agonist during the study.
  * Pathologically confirmed HR-positive male/female breast cancer patients with evidence of localized recurrence or metastasis, who are not suitable for curative surgery or radiation therapy:

ER-positive and/or PR-positive defined as the proportion of positively stained tumor cells ≥ 1% of all tumor cells (as confirmed by the investigators at the participating center).

* Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
* No prior systemic treatment or currently receiving CDK4/6 inhibitors as first-line treatment for advanced disease.
* Reproductive-age females must have a negative serum pregnancy test within 28 days before enrollment and male/female patients must be willing to use a medically approved highly effective contraceptive measure during the study period and up to 1 year after the last dose of investigational drug.
* Non-pregnant or non-lactating females.
* Not concurrently participating in any other ongoing study.
* Patient or legally authorized representative has provided informed consent and is willing and able to comply with the planned visits, study treatment plan, laboratory tests, and other trial procedures.

Exclusion Criteria:

* 1\. Any evidence of severe or uncontrolled systemic illnesses, including uncontrolled hypertension, active bleeding disorders, active infections including hepatitis B, hepatitis C, and human immunodeficiency virus, or severely impaired bone marrow reserve or organ function, including liver and kidney impairment, which, in the investigator's opinion, would greatly alter the risk/benefit balance.
* Patient has not yet recovered from any CTCAE grade ≥ 3 toxicity related to prior treatment at the start of CDK4/6 inhibitor therapy.
* Known history of allergy to CDK4/6 inhibitors, excipients, or drugs with a similar chemical structure or class as CDK4/6 inhibitors.
* Patients deemed unsuitable for enrollment by the investigator.

Where this trial is running

Changsha, Hunan

• Hunan Cancer Hospital — Changsha, Hunan, China (RECRUITING)

Study contacts

• Study coordinator: Ning Xie, Dr.

Conditions: Breast Cancer, Endocrine Therapy, CDK4/6 Inhibitors, Subsequent Treatment