Professor Qingyuan Zhang: Treatment Strategies for HR+/HER2- Advanced Breast Cancer Patients After Progression on CDK4/6i+ET

Editor’s Note: While CDK4/6 inhibitors plus endocrine therapy (ET) have become the standard first-line treatment for HR+/HER2- advanced breast cancer patients, there is currently no standardized recommendation for treatment strategies after progression on CDK4/6 inhibitors plus ET. At the “2024 National Breast Cancer Conference,” “Oncology Frontier” had the privilege of inviting Professor Qingyuan Zhang from Harbin Medical University Cancer Hospital to discuss the factors to consider and the available treatment strategies for patients who have progressed on CDK4/6 inhibitors plus ET.

Oncology Frontier: CDK4/6 inhibitors plus ET have become the standard first-line treatment for HR+/HER2- advanced breast cancer patients. However, there is no standardized recommendation for treatment strategies after progression on CDK4/6 inhibitors plus ET. Could you please introduce the available treatment strategies for HR+/HER2- advanced breast cancer patients after progression on CDK4/6 inhibitors plus ET, with reference to the 2024 CSCO BC guidelines?

Professor Qingyuan Zhang: CDK4/6 inhibitors plus ET have indeed become the standard treatment for HR+/HER2- advanced breast cancer patients, and many patients receive this regimen as first-line treatment in the advanced setting. However, there is currently no gold standard in our guidelines for the treatment of patients who have progressed on CDK4/6 inhibitors plus ET. Therefore, treatment recommendations need to be individualized based on the specific circumstances of each patient, including previous treatment regimens, the duration of benefit from endocrine therapy, and whether patients can obtain pathological tissue after disease progression, to make more precise treatment decisions.

If patients have benefited from previous endocrine therapy for a long time, we can consider switching to another endocrine combination therapy, such as switching to another CDK4/6 inhibitor or a different endocrine therapy drug. For example, if patients have previously received AI therapy for endocrine treatment, we can switch to SERD therapy.

Nowadays, breast cancer has entered the era of precision treatment. For breast cancer patients whose economic conditions allow, clinicians will recommend genetic testing. If patients have alterations in the PI3K/AKT/mTOR signaling pathway (PAM pathway), we can use different drugs for targeted therapy. If patients have PIK3CA mutations, we can use the PI3K inhibitor Alpelisib for treatment. For patients with PIK3CA mutations, the combination of PI3K inhibitor Inavolisib with Palbociclib and Fulvestrant therapy also has good efficacy and safety. In addition, the combination of mTOR inhibitor Everolimus with endocrine therapy for HR+/HER2- metastatic breast cancer patients who have progressed on CDK4/6 inhibitor therapy also provides good progression-free survival benefits.

In addition to the above three pathway inhibitors, for patients who are resistant to endocrine therapy combined with CDK4/6 inhibitors, novel ADC drugs also show good treatment efficacy. The DB-04 study targeting HER2-low population has confirmed that compared to chemotherapy, T-DXd can provide survival benefits for HER2-low expression breast cancer patients regardless of HR status. Moreover, Trop-2 ADC also has good clinical data and can be considered as a clinical treatment option for patients.

Overall, when selecting treatment drugs for patients, it is essential to consider the patient’s physical condition and treatment willingness. In my clinical practice, I will also choose drugs based on the patient’s overall condition. In addition, we will conduct translational research to help patients make treatment decisions. For example, we will use patient tissue for organoid culture and then screen drugs in vitro, which is also helpful for patients in selecting drug treatments.