Supplementary Figure S7 from <i>CCNE1</i> and <i>PLK1</i> Mediate Resistance to Palbociclib in HR+/HER2− Metastatic Breast Cancer
Ángel Guerrero-ZotanoStefania BelliChristoph ZielinskiMiguel Gil‐GilAntonio Fernández‐SerraManuel Ruíz-BorregoEva CiruelosJavier PascualMontserrat MuñozBegoña BermejoMireia Margelí VilaAntonio AntónLaura MurilloBella NissenbaumYuan LiuJesús HerránzDaniel Fernández-GarcíaRosalía CaballeroJosé Antonio López‐GuerreroRoberto BiancoLuigi FormisanoNicholas C. TurnerMiguel Martín
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<p>Generation and characterization of ER+ breast cancer cell lines resistant to palbociclib alone or in combination with fulvestrant</p>Keywords:
Palbociclib
The introduction in clinical practice of selective cyclin-dependent kinase (CDK) 4/6 inhibitors improves the outcome of patients with hormone receptor (HR)-positive human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (mBC). In Romania, the three available CDK 4/6 inhibitors (Palbociclib, Ribociclib and Ademaciclib) have been approved by the National Agency for Medicines (ANM) in 2019, 2020 and 2021. We conducted a retrospective study from 2019 to 2022 on 107 patients with metastatic breast cancer HR+ that have been treated with CDK 4/6 inhibitors in addition to hormone therapy in the Oncology Department of Colțea Clinical Hospital in Bucharest. The purpose of this study is to calculate the median progression-free survival (PFS) and to compare it with the median PFS from other randomized clinical trials. A key difference from other studies is that our study evaluated both patients with non-visceral mBC and patients with visceral mBC, as these two groups often have different outcomes. A total of 79.4% were postmenopausal patients and 20.6% were premenopausal; 42.1% had different stages at the beginning of disease and 57.9% presented newly metastatic disease. Median PFS was 17 months, unlike randomized clinical trials which reported a median PFS of 25.3 months. The combination of CDK 4/6 inhibitors with endocrine therapy is the golden standard treatment in HR-positive, HER2-negative metastatic breast cancer, bringing a prolongation of survival for these patients. Our results show no major differences compared to randomized clinical trials, despite the smaller patient group. In order to have a picture of the efficacy of the treatment as close as possible to the real-world data, we believe that it would be very useful to have a collaboration between several oncology departments in different institutions to carry out a multi-center study on large groups of patients.
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CDK4/6 inhibitors in the first and second treatment line in patients with HR+/HER2- metastatic breast cancer (mBC) in combination with hormonal therapy improve progression-free survival. Role of CDK4/6 inhibitors in further treatment lines remains unclear.Retrospective analysis of 24 HR+/HER2- heavily pretreated mBC patients is presented.A total of 58.3% patients achieved stable disease. No objective response was observed. Median progression-free survival was 4.8 months; median overall survival was 11 months. Treatment was well tolerated.Favorable toxicity profile and efficacy of palbociclib/aromatase inhibitors combination in heavily pretreated luminal mBC patients in this study emphasize the need for further investigation of such drugs in this population.
Palbociclib
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Palbociclib
Fulvestrant
HER2 negative
Progression-free survival
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Palbociclib
Lapatinib
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Palbociclib
Fulvestrant
Exemestane
Aromatase inhibitor
Cyclin-dependent kinase 4
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Palbociclib
Letrozole
Progression-free survival
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Palbociclib
Letrozole
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Palbociclib
HER2 negative
Cyclin-dependent kinase 4
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Ribociclib, palbociclib and abemaciclib are currently approved CDK4/6 inhibitors along with aromatase inhibitors as the first-line standard-of-care for patients with hormone receptor-positive, HER2-negative metastatic breast cancer.
Palbociclib
Letrozole
Aromatase inhibitor
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This study investigated the efficacy of continuing cyclin-dependent kinase (CDK) 4 and 6 inhibitors in patients with estrogen receptor-positive (ER+) human epidermal growth factor receptor 2-negative (HER2- ) metastatic breast cancer (MBC) after disease progression on prior-palbociclib combined with endocrine therapy (ET).This retrospective study based on 25 ER+/HER2- MBC patients reported the efficacy and predictive factors of subsequent-abemaciclib after disease progression on prior-palbociclib.The overall response rate and clinical benefit rate were 16.0% and 44.0%, respectively. The median progression-free survival (PFS) was 5.3 months. In multivariate analysis, the best overall response (BOR) to prior-palbociclib was the only independent predictive factor for PFS (p=0.015). The median time to chemotherapy was 33.9 months. The median PFS in patients treated with next-line chemotherapy after progression on subsequent-abemaciclib was 6.2 months.BOR to prior-palbociclib was the only independent predictive factor for PFS in ER+/HER2- MBC patients undergoing subsequent-abemaciclib after disease progression on prior-palbociclib.
Palbociclib
Progression-free survival
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