873P - Identification of PIK3CA mutation as a novel predictor of efficacious immunotherapy in head and neck cancer

Background

PIK3CA mutations led to the activation of PI3K-AKT-mTOR signaling pathway. This pathway controls cell proliferation, growth, differentiation, migration, and apoptosis. In clinical practice, only a minority of patients with HNSC derive benefit from immunotherapy and the need for the discovery of novel biomarkers to optimize treatment strategies is becoming increasingly more relevant. Whether mutations of PIK3CA are associated with clinical efficacy of immunotherapy (ICIs) in HNSC have not been reported.

Methods

We used cBioportal to collected clinical and mutation data of the MSKCC cohort including 139 patients receiving ICIs. Gene expression data and WES mutation data of 502 samples in the TCGA were obtained for further analysis of the potential biological mechanisms between PIK3CA-MT and PIK3CA-WT tumors. TMB was calculated as the total number of somatic non-synonymous mutations per megabase in both MSKCC and TCGA cohorts. CIBERSORT algorithm was applied to infer 22 human immune cell type proportions in TCGA HNSC.

Results

The TMB level of PIK3CA-Mut patients was higher than PIK3CA-WT patients in both MSKCC (Median [IQR]: 7.02[4.92-10.53] vs. 4.91[2.63-7.90], P=0.006) and TCGA (Median [IQR]: 3.03[1.98-4.42] vs. 2.62[1.66-3.92], P=0.045) cohort. In MSKCC cohort, compared to PIK3CA-WT patients, the PIK3CA-Mut patients achieved prolonged OS (median OS: 25.0 vs. 9.0 months, HR (95%CI): 0.51(0.27-0.94), P=0.029). Moreover, a multivariable analysis across the MSKCC cohort using Cox proportional-hazards regression demonstrated that PIK3CA-Mut was associated with better OS (HR= 0.49; 95%CI, 0.26-0.91; P=0.025), after adjusting for age, gender, metastasis and treatment. Then we used CIBERSORT to explore infiltration of immune cells and two types of immune cells (CD8+ T-cells, CD4+ naïve T-cells) were higher expression in PIK3CA-Mut tumors (P<0.05). These results indicated PIK3CA-Mut tumors had an activated antitumor immune microenvironment.

Conclusions

PIK3CA-Mut is associated with higher TMB in ICI-treated HNSC patients. Survival analysis shows PIK3CA-Mut have a good link with longer OS after immunotherapy. These findings indicate that PIK3CA mutation may serve as a potential predictive biomarker for ICIs in HNSC.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.