Implementation of CDK4/6 Inhibitors and its Influence on the Treatment Landscape of Advanced Breast Cancer Patients – Data from the Real-World Registry PRAEGNANT

Abstract

Background Comprehensive data from prospective clinical trials have led to a high level of evidence establishing CDK4/6 inhibitors in combination with endocrine treatment (CDK4/6i + ET) as a standard for the treatment of HER2-negative, hormone receptor-positive (HER2− HR+) breast cancer patients in the first-line advanced therapy setting. Data on patient populations that have been treated in the real-world setting may provide an insight into changes of patient characteristics and prognosis over time. Methods The data were extracted from the prospective real-world registry PRAEGNANT (NCT02338167). Patients had to have HER2− HR+ advanced breast cancer in the first-line metastatic setting. The chosen therapies were described as well as progression-free survival (PFS) and overall survival (OS) in relation to the given therapies and time periods during which they were indicated. Results CDK4/6 inhibitors have been rapidly implemented since their introduction in November 2016. In recent years (2018 – 2022), about 70 – 80% of the patient population have been treated with CDK4/6 inhibitors, while endocrine monotherapy was given to about 10% and chemotherapy to about 15% of all patients. The prognosis was worst in patients treated with chemotherapy. Recently, mainly patients with a good prognosis are being treated with endocrine monotherapy, and patients who are treated with chemotherapy have an unfavorable prognosis. The PFS and OS of patients treated with CDK4/6i + ET have remained similar over time despite changes in patient characteristics. Conclusion A treatment with CDK4/6i + ET has rapidly become the therapy standard for patients in the first-line advanced breast cancer setting. After the implementation of CDK4/6i + ET, endocrine monotherapy is only given to patients with a very favorable prognosis, while chemotherapy is provided to patients with a rather unfavorable prognosis. These changes in patient characteristics did not seem to influence the prognosis of patients treated with CDK4/6i + ET.

Update Breast Cancer 2022 Part 6 – Advanced-Stage Breast Cancer

“…Auch wenn Chemotherapien bei Patientinnen mit fortgeschrittenem HRpos/HER2neg Mammakarzinom nicht die Therapie der Wahl sind, so ist insbesondere nach einer CDK4/6-Inhibitor-Therapie in der ersten Therapielinie [44] die Chemotherapie in den folgenden Therapielinien eine häufige Therapieoption [45]. Jedoch sind viele dieser Therapien von einem kurzen medianen progressionsfreien Überleben gekennzeichnet [46,47].…”

“…Even though chemotherapy is not the treatment of choice in patients with advanced HRpos/HER2neg breast carcinoma, it is often used as a treatment option in subsequent therapy lines [45], especially following first-line therapy with CDK4/6 inhibitors [44]. However, many of these therapies are characterized by short median progression-free survival times [46,47].…”

CDK4/6 Inhibitors—Overcoming Endocrine Resistance Is the Standard in Patients with Hormone Receptor-Positive Breast Cancer

“…While, according to a German breast cancer registry, in 2015, almost 40% of the first-line patients received chemotherapy, this rate was significantly reduced by 2018 to 25% when all three inhibitors were available [ 37 ]. Three years later, in 2021, already, almost 75% of the first-line population was treated with a CDK4/6i and only 15% with chemotherapy [ 38 ]. This rapid implementation of CDK4/6i in the treatment of aBC caused further investigations regarding its comparability to chemotherapy.…”

Update Breast Cancer 2022 Part 4 – Advanced-Stage Breast Cancer

“…For patients with HER2-negative HR-positive advanced breast cancer, all endocrine therapy options should first be exhausted 7 . However, real-world data show that even after the introduction of CDK4/6 inhibitors, about 40 – 50% of patients in the second or third line of therapy are still treated with chemotherapy 8 , while about 80% of patients are already treated with a CDK4/6 inhibitor 9 in the first line of therapy. An improvement in the therapy situation for these patients would mean a significant progress in therapy.…”

“…80% der Patientinnen bereits in der 1. Therapielinie mit einem CDK4/6-Inhibitor behandelt werden 9 . Eine Verbesserung der Therapiesituation für diese Patientinnen würde einen deutlichen Therapiefortschritt bedeuten.…”