Abstract P4-01-41: Clinical outcome and toxicity profile of Cyclin-dependent kinase 4/6 inhibitors in combination with hormonal treatment in management of metastatic breast cancer patients: A Middle-East Real World Experience
Authors: Gad Ahmed Mostafa , AlSayed Adhar , AlShibani Aisha , Twegieri Taher , Suleman Kausar , Ajarim Dahish 
Published: March 2023

Abstract
Background: Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors in combination with hormonal treatment is the standard of care in the management of hormone receptor positive, human epidermal growth factor receptor-2 (Her2) negative metastatic breast cancer (MBC) patients. Data coming from the Middle east region is very rare and our patients’ population were poorly represented in the CDK4/6 inhibitors landmark clinical trials, This retrospective study is to evaluate our real-world experience with this treatment combination in our patients’ population. Patients and methods: A retrospective study was conducted in a middle eastern tertiary institution, where the clinical data of treatment outcome and toxicity were collected from the electronic medical records of 164 patients with hormone receptor positive, Her2 negative MBC who were managed with CDK4/6 inhibitors in combination with hormonal treatment, at and beyond first line of treatment. Progression free survival (PFS) was the study primary objective, Objective response rate (OR), Overall survival (OS), and toxicity profile were the secondary objectives. Results: From January 2017 to April 2021, 164 patients (5 men and 159 women) were managed with CDK4/6 inhibitors in combination with hormonal treatment for MBC, median age was 52 years (IQR: 45-59), 63% of patients were postmenopausal, 60% had luminal type B tumors, 22% had Her2 expression of 2+ by IHC, 55% had de Novo metastases, 67% had visceral metastases, 61% defined to have endocrine resistant disease (13% primary and 48% secondary resistance), CDK inhibitors (46% Palbociclib, 54% Ribociclib) were given as 1st, 2nd and beyond 2nd line in (48%, 28% and 24% respectively), at a median duration of follow up of 25.3 months (IQR: 13.8-33.9 months), the median PFS for the overall group was 14.2 months (CI 09.8-18.7), it was highest for 1st line treatment 19 months vs 15 and 5 months for the 2nd and beyond 2nd line treatment respectively. The median overall survival was 51.6 months (CI 35.8-67.5) for the whole group, 50.3 and 51.6 months for 1st and 2nd line vs 33.1 months for beyond 2nd line treatment. 5% of patients had achieved complete response, 37% partial response, and 24% had stable disease, with a clinical benefit rate of 74%. A body mass index (BMI) &lt; 30, KI67 &lt; 20%, luminal type A, de Novo metastases, Ribociclib as a CDKi, Aromatase inhibitor (AI) as the hormonal partner, and introducing the treatment combination in early treatment lines (1st and 2nd lines) were all associated with significantly higher PFS in univariate analysis. BMI and AI were the only factors associated with significantly higher PFS in multivariate analysis. Efficacy was consistent regardless of the menopausal status, type of endocrine resistance, and site of metastases. The most common toxicities were neutropenia, fatigue, vomiting, diarrhea, QTC prolongation and hepatic toxicity, the most common G3&4 toxicity were Neutropenia 56%, hepatic toxicity 5.4% and QTC prolongation in 4.3%. Treatment was permanently stopped because of toxicity in 12 patients (7.3%). Conclusion: Our real-life data came consistent with the pivotal clinical trials’ results, encouraging and supporting the use of CDK 4/6 inhibitors in combination with hormonal treatment in our patient population with metastatic breast cancer, especially in the early treatment lines, deferring the start of more toxic therapies to a later stage.
Citation Format: Ahmed Mostafa Gad, Adhar AlSayed, Aisha AlShibani, Taher Twegieri, Kausar Suleman, Dahish Ajarim. Clinical outcome and toxicity profile of Cyclin-dependent kinase 4/6 inhibitors in combination with hormonal treatment in management of metastatic breast cancer patients: A Middle-East Real World Experience. [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-01-41.