Pneumologie 2020; 74(S 01): 127-128
DOI: 10.1055/s-0039-3403352
Freie Vorträge (FV14) – Sektion Pneumologische Onkologie
Aktuelle Systemtherapie des Lungenkarzinoms
Georg Thieme Verlag KG Stuttgart · New York

Evaluation of combined biomarkers for tumor response to immunotherapy (I/O) in patients with advanced non-small cell lung cancer (NSCLC)

H Ramdani
1   Carl von Ossietzky University Oldenburg, Pius Hospital, University of Groningen – University Medical Center Groningen
,
M Falk
2   Lung Cancer Network Nowel, Institut for Hematopathology Hamburg
,
S Schatz
2   Lung Cancer Network Nowel, Institut for Hematopathology Hamburg
,
LC Heukamp
2   Lung Cancer Network Nowel, Institut for Hematopathology Hamburg
,
M Tiemann
2   Lung Cancer Network Nowel, Institut for Hematopathology Hamburg
,
E Schuuring
3   University of Groningen – University Medical Center Groningen
,
H Groen
3   University of Groningen – University Medical Center Groningen
,
F Griesinger
4   Carl von Ossietzky University of Oldenburg, Pius Hospital Oldenburg, Lung Cancer Network Nowel
› Institutsangaben
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Publikationsverlauf

Publikationsdatum:
28. Februar 2020 (online)

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    Background: 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.

    Methods: 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.

    Results: 43/54 pts received nivolumab, 11/54 pembrolizumab in different therapy lines (from 1st to 5th). 24 pts were defined as having a durable tumor response (median PFS44 months, median OS53 months; p < 0.0001) 30 pts as primary progressors (median PFS2 months, median OS12 months; p < 0.0001). In 30/54 pts enough material was available for TMB testing. 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 the biomarkers will be presented at the meeting as well as correlative data of the parameters analyzed.

    Conclusion: 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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