Abstract
Immunohistochemical expression of ER and p53 as predictive biomarkers of immunotherapy in endometrial cancer.
Author
Michael Liontos
Alexandra Hospital, School of Medicine, Athens, Greece
info_outline
Michael Liontos, Aristea-Maria Papanota, Anna Svarna, Vasileios Pergialiotis, Oraianthi Fiste, Christos Markellos, Elena Kunadis, Eirini Potiri, Angeliki Andrikopoulou, Alkistis Papatheodoridi, Konstantinos Koutsoukos, Maria Kaparelou, Kalliroi Goula, Kitty Pavlakis, Nikolaos Thomakos, Dimitrios Haidopoulos, Alexandros Rodolakis, Flora Zagouri, Meletios A. Dimopoulos
Full text
Authors
Michael Liontos
Alexandra Hospital, School of Medicine, Athens, Greece
info_outline
Michael Liontos, Aristea-Maria Papanota, Anna Svarna, Vasileios Pergialiotis, Oraianthi Fiste, Christos Markellos, Elena Kunadis, Eirini Potiri, Angeliki Andrikopoulou, Alkistis Papatheodoridi, Konstantinos Koutsoukos, Maria Kaparelou, Kalliroi Goula, Kitty Pavlakis, Nikolaos Thomakos, Dimitrios Haidopoulos, Alexandros Rodolakis, Flora Zagouri, Meletios A. Dimopoulos
Organizations
Alexandra Hospital, School of Medicine, Athens, Greece, Department of Clinical Therapeutics, Alexandra Hospital, Medical School, National & Kapodistrian University of Athens, Athens, Greece, National and Kapodistrian University of Athens, Department of Clinical Therapeutics, Athens, ATTICA, Greece, First dpt of Ob/Gyn, National and Kapodistrian University of Athens, Athens, Greece, Oncology Unit, Third Department of Medicine, National and Kapodistrian University of Athens, Athens, Attica, Greece, Alexandra General Hospital, Agioi Anargyroi-Kamatero, Greece, Alexandra University General Hospital of Athens, Athina, Greece, National and Kapodistrian University of Athens, Department of Clinical Therapeutics, Athens, Greece, National and Kapodistrian University of Athens, School of Medicine, Athens, Greece, Haematology- Oncology Unit, Department Of Clinical Therapeutics, Alexandra Hospital, University of Athens, Athens, Greece, Alexandra General Hospital, National and Kapodistrian University of Athens, School of Medicine, Athens, Greece, Athens University Medical School, Athens, Greece, University of Athens, Athens, Greece, Department of Clinical Therapeutics, National and Kapodistrian University of Athens, Athens, Greece, Alexandra Hospital, Athens, Greece
Abstract Disclosures
Research Funding
No funding received
None.
Background:
Immune Checkpoint Inhibitors (ICIs), either as monotherapy or in combination with tyrosine kinase inhibitors (TKIs), were recently incorporated into the therapeutic guidelines for recurrent/metastatic endometrial cancer (EC). Microsatellite Instability (MSI) is the only biomarker to guide treatment. We evaluated the predictive significance of Estrogen Receptor (ER) and p53 expression.
Methods:
Medical charts of EC patients that received ICIs in our institution for advanced/metastatic disease were retrospectively reviewed. TP53 and ER expression were determined by immunohistochemistry. Survival analysis was performed using IBM SPSS statistics v.25.
Results:
Thirty-two patients were included in our analysis. The median age was 63.1 years (25
th
-75
th
percentile: 57.6 – 69.6). 62.5% of the patients had endometrioid histology, 21.9% serous histology and 15.6% of them displayed other histology. 46.9% of the patients had grade 1-2 tumors and 53.1% grade 3 tumors. 21.9% of them were diagnosed with stage 1-2 disease, while 78.1% presented with stage 3 disease. 62.5% received 0-1 prior lines of treatment and 37.5% of them received more than 2 prior lines. Molecular characteristics are presented in the table. All MSI-High patients received anti-PD1 monotherapy with a median PFS of 11.9 months (95% CI:2.3-21.5). Microsatellite Stable (MSS) patients received pembrolizumab-lenvatinib combination with median PFS 7.54 months (95% CI:2.6-11.5). ER positivity was associated with significant PFS benefit in both the ICI monotherapy group (11.9 vs. 0.63 months, p=0.061) and the group that received ICI/TKI combination (11.3 vs. 1.75 months, p=0.001). Analogous benefit was noted in the Overall Survival post start of IO or IO/TKI treatment (9.8 vs 0.6 months in MSI-high patients and 20.6 vs 5.9 months in MSS patients). ER-positivity remained an independent predictive factor favoring PFS in the Multivariate Cox regression analysis when adjusting for immunotherapy type, histology, and previous lines of therapy (HR=0.216, p=0.013).
Conclusions:
ER expression proved to be an independent prognostic factor regarding PFS in our cohort of patients. Further studies are needed to investigate the role of ER as a predictive biomarker for immunotherapy in EC.
Patients’ molecular characteristics.
Total N(%)
Anti-PD1 N (%)
Anti-PD1/TKI N (%)
TP53 status (IHC)
31 (100%)
12
19
TP53 aberrant
13 (41.9%)
2
11
TP53 wild type
18 (58.1%)
10
8
ER status (IHC)
32
13
19
ER positive
25
11
14
ER Negative
7
2
5
Microsatellite instability
32
13
19
MSI-High/dMMR
13
13
0
MSS/pMMR
19
0
19
11 organizations
3 drugs
4 targets
Organization
National & Kapodistrian University of AthensOrganization
First dpt of Ob/GynOrganization
Oncology Unit S. Chiara Hospital, Trento, ItalyOrganization
Third Department of MedicineOrganization
Alexandra General HospitalOrganization
Alexandra University General Hospital of AthensOrganization
Haematology- Oncology UnitOrganization
University of AthensOrganization
Athens University Medical SchoolTarget
VEGFR-1Target
PD-1Target
PD-L1 (CD274)Target
tyrosine kinase