Evaluation of Biomarker for Response to Immune Chekcpoint Inhibitors in Patients with Advanced Non-Small Cell Lung Cancer

Introduction Immune checkpoint inhibitors (I/O) have revolutionized NSCLC treatment. The only established and therapy stratification relevant predictive marker for I/O is the expression of PD-L1, which is however not reliable due to ist heterogenous expression and independant mode of action. Therefore, novel biomarkers are needed to better predict tumour response (positive and negative predictive). Thus, the establishment of new predictive markers such as positive predictive markers (Tumour Mutational Burden) or negative predictive markers such as the expression of CD73 is of interest.

Methods A retrospective study will be performed on a cohort of 50 pts with advanced NSCLC from two institutions (cross border Germany and Netherlands) that have been treated with I/O. The pts were selected by availability of material and their response to I/O: good response (more than 6 months PR) or bad response (PD as best response). 25 pts from each category will be selected based on the DNA yield. On these ptsʼ samples two tests will be performed, namely: Hybrid Capture NGS assay from NEO New Oncology (NEO Plus) and the Foundation1 CDx test. IHC tests will also be performed on the tumor samples to estimate the expression of both PD-L1 and CD73.

Results 54 pts were selected from the first institution (Oldenburg, Germany). These pts received I/O, either Nivolumab (n = 43) or Pembrolizumab (n = 11), between 2015 and 2017 in different therapy lines (from 1st to 6th line). 24 pts were good responders and 30 pts bad responders. 21 pts are alive, 32 deceased and 1 lost to follow-up. From 14 good responders, 4 pts had a PDL1 score TC0, 2 pts had TC1 and 8 pts had TC2; and from 17 bad responders, 6 pts had a TC0, 7 pts TC1 and 4 pts TC2. The median PFS under I/O for good responders was 19 months whereas the bad responders had a median PFS of 2 months (p < 0.000). Median OS for the cohort was 30 months. Median OS in the good responders was 42 months while the bad responders had a median OS of 17 months (p < 0.000).

Conclusion Significant difference in both PFS and OS between good responders and bad responders were observed. The TC PD-L1 score available shows the heterogeneity of PD-L1 as a positive predictive biomarker and thus the need for new positive and negative predictive biomarkers for I/O. Results of the TMB and IHC analyses (CD73) will be presented at the meeting.