P2.04-63 Evaluation of Combined Biomarkers for Tumor Response to Immunotherapy (I/O) in Patients with Advanced Non-Small Cell Lung Cancer (NSCLC)
JOURNAL OF THORACIC ONCOLOGY(2019)
Abstract
Immune checkpoint inhibitors have revolutionized NSCLC treatment. At present, the only established predictive biomarker for I/O-therapy stratification are PD-L1 expression and MSI status. However, the expression of PD-L1 is limited by heterogeneous expression and even high expressors not always respond to I/O therapy. The aim of the study is to evaluate the value of combinations of positive (Tumor Mutational Burden, PD-L1) and negative (a.o. CD73 expression and inactivating STK11 mutations) predictive markers in patients (pts) with advanced NSCLC on I/O therapy. A retrospective study was performed on a cohort of 54 pts with advanced NSCLC that have been treated with I/O between 2015 and 2018. Pts were selected by the availability of tumor tissue and based on tumor response evaluated by RECIST v1.1 criteria: only patients with durable tumor response (CR, PR ≥ 6 months) and patients with no tumor response (PD as best response) were analyzed for biomarkers: hybrid capture NGS assay for TMB (New Oncology) including STK11 mutations and IHC tests for PD-L1, CD73 and VISTA. Adjusted Cox regression and ROC analysis will be performed to evaluate the predictive value of the different biomarkers. 43/54 pts received nivolumab, 11/54 pembrolizumab in different therapy lines (from 1st to 5th line). 24 pts were defined as having a durable tumor response (median PFS 20 months, median OS not reached) 30 pts as primary progressors (median PFS 2 months, p<0.0001), median OS 12 months, p<0.0001). In 30/54 pts enough material was available for TMB testing. The median TMB-value is 11.42 mutations/Mb. In 13 durable responders median TMB-value was 13.28 mutations/Mb versus 11.00 mutations/Mb in 17 primary non-responders. STK11 mutations were observed in 3/17 primary non-responders (10%) vs. 0/13 in durable responders (0%). Additional analyses of PD-L1, CD73, and VISTA will be presented at the meeting as well as correlative data of the parameters analysed. Our results suggest that integrating several biomarkers including positive and negative predictive markers may correlate better with responses to I/O than PD-L1 and TMB alone.
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Key words
NSCLC,Immune Checkpoint Inhibitors,tumor mutational burden
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