877P - ROS1 mutations as potential negative predictor for response of immunotherapy in patient with head and neck cancer

Background

The c-ros oncogene 1 (ROS1) gene has aroused great research interest for its role as an oncogenic driver of malignancies, as well as its untapped potential for novel therapeutic target. Despite the success of targeted therapy in ROS1-rearranged across multiple cancers, there were few studies on variations other than rearrangement concerning ROS1, and what role the ROS1 mutation would act in ICI treatment of Head and Neck cancer (HNSC) has not yet been studied. We sought to elucidate the predictive effect of ROS1 mutation, instead of rearrangement, for the efficacy of immunotherapy in HNSC

Methods

139 HNSC patients with NGS and immunotherapy data obtained from MSKCC cohort were used to explore the association between ROS1 mutation and efficacy of ICIs. TMB was defined as the total number of somatic non-synonymous mutations. The sequencing, mRNA and survival data of 502 patients with HNSC from TCGA was used to explore the underlying mechanism

Results

In the MSKCC cohort, we observed 7 (5.04%) patients harbored ROS1 somatic mutation. As indicated by Kaplan-Meier analysis, the patients with ROS1-Mut had significantly worse OS in the MSKCC cohort (P=0.011, HR=3.22, 95%CI=1.26-8.19). This link was still existing when controlling for age, sex, stage, tumor site type, TMB and therapy type in the multivariate Cox regression analysis (P=0.006, HR=4.08, 95%CI=1.48-11.2). Patients with ROS1-Mut had higher TMB compared to patients with wild-type ROS1 in both MSKCC (P=0.043) and TCGA cohort (P<0.001). While as shown above, ROS1-Mut was an independent indicator of poorer outcomes beyond TMB status, suggesting the negative prognosis of ROS1-Mut receiving ICIs treatment may attribute to other factors. In TCGA, no association was observed between ROS1-Mut and survival (P=0.26). These results suggested that ROS1-Mut was a potential negative predictor for immunotherapy, instead of a prognosis factor for HNSC. Immune cell analysis showed that Regulatory Tregs T-cells were significantly less abundant in the ROS1-Mut group (P=0.037), indicating an deactivated antitumor immune microenvironment.

Conclusions

We identified that ROS1 mutation predicted the resistance to ICIs in HNSCs. The clinical delivery of ICIs should be cautious in those patients.

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.