Abstract 873P
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.
Resources from the same session
942P - Response to salvage chemotherapy with paclitaxel +/- cetuximab after progression on immune checkpoint inhibitors in platinum-refractory recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN) patients (CeTax study)
Presenter: Ruth Gabriela Herrera Gomez
Session: Poster session 12
944TiP - Randomized phase II study of immune stimulation with pembrolizumab and radiotherapy of recurrent and/or metastatic head and neck squamous cell carcinoma : The IMPORTANCE trial
Presenter: Bálint Tamaskovics
Session: Poster session 12
1089P - Adjuvant nivolumab (NIVO) vs ipilimumab (IPI) in resected stage III/IV melanoma: 7-y results from CheckMate 238
Presenter: Paolo Ascierto
Session: Poster session 12
1090P - Outcome impact of time from complete resection to start of adjuvant immunotherapy in stage III-IV melanoma patients
Presenter: Sergio Martinez Recio
Session: Poster session 12
1092P - Adjuvant treatment with anti-PD-1 in acral melanoma patients: A nationwide study
Presenter: Manja Bloem
Session: Poster session 12
1093P - Neoadjuvant (NeoAd) intratumoral (IT) TAVO-EP (plasmid IL-12 electro gene transfer) in combination with nivolumab (NIVO) for patients (pts) with operable locoregionally advanced melanoma
Presenter: Ahmad Tarhini
Session: Poster session 12
1094P - Relapse free survival (RFS) at 3 years by pathological (path) response to neoadjuvant systemic treatment (NST) in patients (pts) with surgically resectable, high-risk melanoma
Presenter: Elizabeth Burton
Session: Poster session 12
1095P - Associations between baseline biomarkers and 3-year survival in the PRADO trial testing neoadjuvant ipilimumab and nivolumab in stage III melanoma
Presenter: Irene Reijers
Session: Poster session 12