The Efficacy And Safety of CDK 4/6 Inhibitors Plus Endocrine Therapy With Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor-2- Negative Metastatic Breast Cancer Patients

INTRODUCTION: Combining cyclin-dependent kinases 4/6 inhibitors with endocrine therapy are indicated as first or second-line treatment for hormone receptor-positive, HER2-negative advanced or metastatic breast cancer.We aimed to investigate the efficacy and safety of adding CDKIs to endocrine therapy in patients whose tumors might have differing degrees of endocrine sensitivity.
METHODS: Totally, 99 patients with HR+, HER2-, ABC who received CDK4/6 inhibitor
and hormonotherapy were included.Clinicopathological features of patients and progression-free survival (PFS) and overall survival (OS) outcomes were analyzed.The toxicity, combine drugs and the factors that may predict survival were also evaluated.


RESULTS: This study with a median age of 51 years (range;31-80).The molecular subtypes of the patients were as follows;51 patients (51.5%) were in the luminal A group, and 48 patients (48.5%) were in the luminal B HER2- group. Before CDK 4/6 inhibitor therapy, visceral and non-visceral metastasis were seen in 48 and 46 patients, respectively.At the median follow-up time of 13.7 months (range: 3-48 months), the median OS was 38.5 months, the median PFS was 5.2 months. Univariate analysis demonstrated that the choice of CDK 4/6 agent was significantly associated with PFS. 6-months PFS rate with ribociclib was 42.3%, in palbociclib, it was 63.6%, in abemaciclib it was NA (not aplicable) (p=0.01).Univariate analysis revealed that the luminal type of tumor (p=0.002), advanced stage disease at the initial diagnosis (p<0.001), and presence of visceral metastasis (p=0.006) were significant factors for OS.
DISCUSSION AND CONCLUSION: In this study we demonstrated that there is a survival benefit for all three agents and there is a significant difference especially between first and second-line usage.

Hormon Reseptörü-Pozitif, Ýnsan Epidermal Büyüme Faktörü Reseptörü-2-Negatif Metastatik Meme Kanseri Hastalarýnda CDK 4/6 Ýnhibitörleri ile Endokrin Tedavisinin Etkinliði ve Güvenliði

GÝRÝÞ ve AMAÇ: Sikline baðýmlý kinaz 4/6 inhibitörlerinin endokrin terapi ile birleþtirilmesi, hormon reseptörü pozitif, HER2 negatif ilerlemiþ veya metastatik meme kanseri için birinci veya ikinci basamak tedavi olarak endikedir. Tümörleri farklý derecelerde endokrin duyarlýlýða sahip olabilecek hastalarda endokrin tedaviye CDKI'lerin eklenmesinin etkinliðini ve güvenliðini araþtýrmayý amaçladýk.
YÖNTEM ve GEREÇLER: CDK4/6 inhibitörü ve hormon tedavisi alan HR+, HER2-, ABC'li toplam 99 hasta dahil edildi. Hastalarýn klinikopatolojik özellikleri ve progresyonsuz (PFS) ve genel saðkalým (OS) sonuçlarý analiz edildi. Toksisite, kombine ilaçlar ve saðkalýmý öngörebilecek faktörler de deðerlendirildi.
BULGULAR: Ortanca yaþý 51 (31-80) olan bu çalýþmada hastalarýn moleküler alt tipleri þöyleydi; 51 hasta (%51,5) lümen A grubunda, 48 hasta (%48,5) lüminal B HER2-grubunda.CDK 4/6 inhibitör tedavisi öncesi sýrasýyla 48 ve 46 hastada visseral ve visseral olmayan metastaz görüldü. Medyan 13,7 aylýk takip süresinde (daðýlým: 3-48 ay), medyan OS 38,5 aydý, medyan PFS 5.2 aydý. Tek deðiþkenli analiz, CDK 4/6 ajaný seçiminin PFS ile önemli ölçüde iliþkili olduðunu gösterdi. Ribosiklib ile 6 aylýk PFS oraný %42,3, palbosiklib ile %63,6, abemaciclib ile NA idi (p=0,01). Tek deðiþkenli analiz tümörün lüminal tipi (p=0,002), ilk taný anýndaki ileri evre hastalýk (p<0,001) ve visseral metastaz varlýðýnýn (p=0,006) OS için anlamlý faktörler olduðunu ortaya koydu.
TARTIÞMA ve SONUÇ: Bu çalýþmada, her üç ajan için de saðkalým yararý olduðunu ve özellikle birinci ve ikinci basamak kullaným arasýnda anlamlý bir fark olduðunu gösterdik.