Efficacy of subsequent treatments in patients with hormone-positive advanced breast cancer who had disease progression under CDK 4/6 inhibitor therapy
Authors: Karacin Cengiz , Oksuzoglu Berna , Demirci Ayşe , Keskinkılıç Merve , Baytemür Naziyet Köse , Yılmaz Funda , Selvi Oğuzhan , Erdem Dilek , Avşar Esin , Paksoy Nail , Demir Necla , Göksu Sema Sezgin , Türker Sema , Bayram Ertuğrul , Çelebi Abdüssamet , Yılmaz Hatice , Kuzu Ömer Faruk , Kahraman Seda , Gökmen İvo , Sakin Abdullah , Alkan Ali , Nayır Erdinç , Uğraklı Muzaffer , Acar Ömer , Ertürk İsmail , Demir Hacer , Aslan Ferit , Sönmez Özlem , Korkmaz Taner , Celayir Özde Melisa , Karadağ İbrahim , Kayıkçıoğlu Erkan , Şakalar Teoman , Öktem İlker Nihat , Eren Tülay , Erul Enes , Mocan Eda Eylemer , Kalkan Ziya , Yıldırım Nilgün , Ergün Yakup , Akagündüz Baran , Karakaya Serdar , Kut Engin , Teker Fatih , Demirel Burçin Çakan , Karaboyun Kubilay , Almuradova Elvina , Ünal Olçun Ümit , Oyman Abdilkerim , Işık Deniz , Okutur Kerem , Öztosun Buğra , Gülbağcı Burcu Belen , Kalender Mehmet Emin , Şahin Elif , Seyyar Mustafa , Özdemir Özlem , Selçukbiricik Fatih , Kanıtez Metin , Dede İsa , Gümüş Mahmut , Gökmen Erhan , Yaren Arzu , Menekşe Serkan , Ebinç Senar , Aksoy Sercan , İmamoğlu Gökşen İnanç , Altınbaş Mustafa , Çetin Bülent , Uluç Başak Oyan , Er Özlem , Karadurmuş Nuri , Erdoğan Atike Pınar , Artaç Mehmet , Tanrıverdi Özgür , Çiçin İrfan , Şendur Mehmet Ali Nahit , Oktay Esin , Bayoğlu İbrahim Vedat , Paydaş Semra , Aydıner Adnan , Salim Derya Kıvrak , Geredeli Çağlayan , Yavuzşen Tuğba , Doğan Mutlu , Hacıbekiroğlu İlhan 
Published: February 2023

Abstract
Background
There is no standard treatment recommended at category 1 level in international guidelines for subsequent therapy after cyclin-dependent kinase 4/6 inhibitor (CDK4/6) based therapy. We aimed to evaluate which subsequent treatment oncologists prefer in patients with disease progression under CDKi. In addition, we aimed to show the effectiveness of systemic treatments after CDKi and whether there is a survival difference between hormonal treatments (monotherapy vs. mTOR-based).

Methods
A total of 609 patients from 53 centers were included in the study. Progression-free-survivals (PFS) of subsequent treatments (chemotherapy (CT, n:434) or endocrine therapy (ET, n:175)) after CDKi were calculated. Patients were evaluated in three groups as those who received CDKi in first-line (group A, n:202), second-line (group B, n: 153) and ≥ 3rd-line (group C, n: 254). PFS was compared according to the use of ET and CT. In addition, ET was compared as monotherapy versus everolimus-based combination therapy.

Results
The median duration of CDKi in the ET arms of Group A, B, and C was 17.0, 11.0, and 8.5 months in respectively; it was 9.0, 7.0, and 5.0 months in the CT arm. Median PFS after CDKi was 9.5 (5.0–14.0) months in the ET arm of group A, and 5.3 (3.9–6.8) months in the CT arm (p = 0.073). It was 6.7 (5.8–7.7) months in the ET arm of group B, and 5.7 (4.6–6.7) months in the CT arm (p = 0.311). It was 5.3 (2.5–8.0) months in the ET arm of group C and 4.0 (3.5–4.6) months in the CT arm (p = 0.434). Patients who received ET after CDKi were compared as those who received everolimus-based combination therapy versus those who received monotherapy ET: the median PFS in group A, B, and C was 11.0 vs. 5.9 (p = 0.047), 6.7 vs. 5.0 (p = 0.164), 6.7 vs. 3.9 (p = 0.763) months.

Conclusion
Physicians preferred CT rather than ET in patients with early progression under CDKi. It has been shown that subsequent ET after CDKi can be as effective as CT. It was also observed that better PFS could be achieved with the subsequent everolimus-based treatments after first-line CDKi compared to monotherapy ET.