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Found 1 Presentation For Request "1481P"
1481P - Expression of ERBB2 and PD1 mRNA in advanced gastric cancer
- David Pesántez Coronel (Barcelona, Spain)
Abstract
Background
Quantitative measurements of ERBB2 and PD1 mRNA in gastric cancer (GC) could better reflect the status of HER2 and the amount of immune infiltration than standard pathology-based methods.
Methods
A retrospective cohort of patients (pts) with advanced GC treated at Hospital Clinic of Barcelona was evaluated. HER2 status was identified by immunohistochemistry (IHC) and/or in situ hybridization (ISH) according to guidelines. ERBB2 and PD1 mRNA levels were measured from archival formalin-fixed paraffin-embedded tumors using the nCounter platform. To compare ERBB2 levels, we evaluated an in-house cohort of 392 breast cancers (BC). Cox models and logistic regressions were used to associate ERBB2 or PD1 expression with progression free survival (PFS) and response following a trastuzumab-based chemotherapy (T-chemo). Descriptive statistics were also used.
Results
75 pts were evaluated, 42(56%) were HER2+ and 28 (67%) pts with HER2+ GC received T-chemo. HER2+ GC had higher ERBB2 levels than HER2 negative (1.6-fold difference; p<0.001). Among HER2+ GC, higher ERBB2 levels were observed in HER2 IHC 3+ than in 2+ tumors (2.4-fold difference; p<0.001); in addition, a large range of ERBB2 levels was observed in HER2 3+ GC (IQR: 6.8-fold). When comparing HER2 3+ BC with GC, ERBB2 levels were higher in BC than GC (4.6-fold; p<0.001). In pts with HER2+ GC treated with T-chemo, overall response rate (ORR) in ERBB2-low (below median) and ERBB2-high groups was 14.3% and 53.4%, respectively (p=0.046). Median PFS in ERBB2-high was 8.1 vs. 3.1 months in ERBB2-low (hazard ratio [HR]=0.51; p=0.112). In this group, ORR and median PFS in HER2 3+ were 38.9% and 5.68 months, and 25.0% and 6.30 months in HER2 2+. PD1 was highly expressed in HER2-negative than HER2+ GC (1.8-fold; p=0.002). Among HER2+ GC treated with T-chemo, ORR in PD1-low (low tertile), PD1-med and PD1-high was 10%, 22.2% and 75%, respectively (p=0.009). In this group, PD1-med/high was significantly associated with better PFS compared to PD1-low (HR= 0.10; p<0.001).
Conclusions
High ERBB2 and PD1 mRNA levels might help identify pts most likely to benefit from trastuzumab-based therapy. The role of immune checkpoint inhibitors in HER2+ GC with high PD1 mRNA requires further investigation.
Legal entity responsible for the study
Hospital Clinic of Barcelona.
Funding
Has not received any funding.
Disclosure
C. Teixido Febrero: Travel/Accommodation/Expenses, Personal fees: MSD; Travel/Accommodation/Expenses, Personal fees: Roche; Travel/Accommodation/Expenses, Personal fees: Pfizer; Travel/Accommodation/Expenses, Personal fees: Novartis; Travel/Accommodation/Expenses, Personal fees: AstraZeneca; Travel/Accommodation/Expenses, Personal fees: Angelini; Travel/Accommodation/Expenses, Personal fees: BMS; Travel/Accommodation/Expenses, Personal fees: Takeda; Travel/Accommodation/Expenses, Personal fees: Diaceutics. A. Prat: Honoraria (self), Lecture fees: Roche; Advisory/Consultancy, Lecture fees, Advisory role/consultancy: Pfizer ; Advisory/Consultancy, Lecture fees, Advisory role/consultancy: Novartis; Advisory/Consultancy, Lecture fees, Advisory role/consultancy: Amgen; Honoraria (self), Lecture fees: BMS; Honoraria (self), Lecture fees: Daiichi Sankyo; Advisory/Consultancy, Advisory role/consultancy: Puma; Advisory/Consultancy: Oncolytics Biotech; Advisory/Consultancy: MSD; Advisory/Consultancy: Lilly; Travel/Accommodation/Expenses, Lecture fees: Nanostring technologies; Officer/Board of Directors, Member of the Board Solti's Foundation: Lecture fees; Officer/Board of Directors, Patronage committee: Actitud frente al cancer Foundation; Officer/Board of Directors, Member Executive Board: Solti; Honoraria (institution), Contracted research, Clinical trials: Boehringer; Honoraria (institution), Clinical trials: Lilly; Honoraria (institution), Contracted research, Clinical trials: RochePzifer; Honoraria (institution), Contracted research: Nanostring technologies; Honoraria (institution), Contract research, Clinical trials: Novartis Farma, SA; Honoraria (institution), Clinical trials: Amgen; Honoraria (institution), Clinical trials: Daiichi Sankyo; Advisory/Consultancy, Contract research: Roche Farma, SA; Advisory/Consultancy, Contract research: Sysmex Europa GmbH; Advisory/Consultancy, Contract research: Medica Scientia inno. Research, SL; Advisory/Consultancy, Contract research: Celgene, SLU; Advisory/Consultancy, Contract research: Astellas Pharma, SA. All other authors have declared no conflicts of interest.