Abstract 965P
Background
Paclitaxel and cetuximab (ERBITAX) is widely used in platin-unfit R/M HNSCC P. STAT3 signaling hyperactivation has been reported to promote development and progression of HNSCC. PTPRT protein acts as a negative regulator of STAT3. Loss of PTPRT function by mutation or promoter hypermethylation induces STAT3 phosphorylation and pathway activation. Paclitaxel decreases STAT3 phosphorylation and transcriptional activity in cell lines. Also, STAT3 is involved in epidermal growth factor receptor pathway, suggesting that may have a role in the response to cetuximab.
Methods
34 P with R/M HNSCC treated with ERBITAX between 2008 and 2017 with available histological sample, clinical information and data on treatment efficacy were included in this retrospective study. STAT3 transcriptional levels were analyzed in 21 of 34 samples using TaqMan expression assays and quantitative real-time PCR technique. Cut-off point between high and low levels was the median value. Phosphorylated and therefore activated STAT3 form (pSTAT3) was analyzed by immunohistochemistry stratifying activation levels as 0, 1, 2 or 3+. PTPRT promoter hypermethylation was analyzed by methylation-specific PCR (MSP).
Results
41% of tumors showed PTPRT promoter hypermethylation, significantly associated with a lower response rate (RR) (21 vs 60%, p=0,026). pSTAT3 overexpression (2 and/or 3+) was detected in 67% of tumors and was correlated with a non-statistically significant lower RR (36 vs 54%, p=0,32), similar to STAT3 mRNA transcriptional levels (43 vs 64%, p=0,098). PTPRT hypermethylation was correlated with pSTAT3 overexpression (p=0,006) but not with the expression levels. Overall survival of P whose tumors had PTPRT hypermethylated or pSTAT3 overexpressed was lower than those who did not have (6 vs 9 months), but this difference was not statistically significant.
Conclusions
Despite the limitations of this retrospective analysis with a small number of P, STAT3 pathway could be an interesting biomarker and therapeutic target that deserves further investigation in HNSCC.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
B. Cirauqui Cirauqui: Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: BMS; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Roche; Advisory/Consultancy, Travel/Accommodation/Expenses: Merck; Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Eisai; Travel/Accommodation/Expenses: Pierre-Fabre; Travel/Accommodation/Expenses: MSD. V. Quiroga García: Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Roche; Travel/Accommodation/Expenses: BMS; Travel/Accommodation/Expenses: Novartis; Travel/Accommodation/Expenses: Pfizer; Advisory/Consultancy: Kern. M. Margeli Vila: Advisory/Consultancy, Speaker Bureau/Expert testimony: Novartis; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Roche; Advisory/Consultancy, Research grant/Funding (institution): Kern; Research grant/Funding (institution): Celgene. R. Mesia Nin: Advisory/Consultancy, Speaker Bureau/Expert testimony: BMS; Advisory/Consultancy, Speaker Bureau/Expert testimony: Merck; Advisory/Consultancy: MSD; Advisory/Consultancy: Roche; Advisory/Consultancy: Nanobiotics. All other authors have declared no conflicts of interest.