Predictive value of PD-L1 based on mRNA level in the treatment of stage IV melanoma with ipilimumab

• Published in: Journal of cancer research and clinical oncology 2017-10, Vol.143 (10), p.1977-1984
• Main Authors: Brüggemann, C., Kirchberger, M. C., Goldinger, S. M., Weide, B., Konrad, A., Erdmann, M., Schadendorf, D., Croner, R. S., Krähenbühl, L., Kähler, K. C., Hafner, C., Leisgang, W., Kiesewetter, F., Dummer, R., Schuler, G., Stürzl, M., Heinzerling, L.
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Antibodies; B7-H1 Antigen - biosynthesis; B7-H1 Antigen - genetics; B7-H1 Antigen - immunology; Cancer Research; Case-Control Studies; Chemotherapy; CTLA-4 protein; Dacarbazine; Female; Gene Expression; Hematology; Humans; Immunohistochemistry; Immunotherapy; Internal Medicine; Ipilimumab - administration & dosage; L1 gene; Male; Medical prognosis; Medicine; Medicine & Public Health; Melanoma; Melanoma - drug therapy; Melanoma - genetics; Melanoma - immunology; Melanoma - pathology; MicroRNAs; Middle Aged; Monoclonal antibodies; Neoplasm Staging; Non-small cell lung carcinoma; Oncology; Original Article – Cancer Research; Paraffin; PD-1 protein; PD-L1 protein; Polymerase chain reaction; Predictive Value of Tests; Real-Time Polymerase Chain Reaction; Retrospective Studies; RNA, Messenger - genetics; RNA, Messenger - metabolism; Skin cancer; Skin Neoplasms - drug therapy; Skin Neoplasms - genetics; Skin Neoplasms - immunology; Skin Neoplasms - pathology; Standardization; Statistical analysis; Targeted cancer therapy
• ISSN: 0171-5216; 1432-1335
• DOI: 10.1007/s00432-017-2450-2

Introduction PD-L1 is established as a predictive marker for therapy of non-small cell lung cancer with pembrolizumab. Furthermore, PD-L1 positive melanoma has shown more favorable outcomes when treated with anti-PD1 antibodies and dacarbazine compared to PD-L1 negative melanoma. However, the role of PD-L1 expression with regard to response to checkpoint inhibition with anti-CTLA-4 is not clear, yet. In addition, the lack of standardization in the immunohistochemical assessment of PD-L1 makes the comparison of results difficult. In this study, we investigated the PD-L1 gene expression with a new fully automated technique via RT-PCR and correlated the findings with the response to the anti-CTLA-4 antibody ipilimumab. Materials and methods Within a retrospective multi-center trial, PD-L1 gene expression was evaluated in 78 melanoma patients in a total of 111 pre-treatment tumor samples from 6 skin cancer centers and analyzed with regard to response to ipilimumab. For meaningful statistical analysis, the cohort was enriched for responders with 30 responders and 48 non-responders. Gene expression was assessed by quantitative RT-PCR after extracting mRNA from formalin-fixed paraffin embedded tumor tissue and correlated with results from immunohistochemical (IHC) stainings. Results and discussion The evaluation of PD-L1 expression based on mRNA level is feasible. Correlation between PD-L1 expression as assessed by IHC and RT-PCR showed varying levels of concordance depending on the antibody employed. RT-PCR should be further investigated to measure PD-L1 expression, since it is a semi-quantitative method with observer-independent evaluation. With this approach, there was no statistical significant difference in the PD-L1 expression between responders and non-responders to the therapy with ipilimumab. The evaluation of PD-L1 expression based on mRNA level is feasible. Correlation between PD-L1 expression as assessed by IHC and RT-PCR showed varying levels of concordance depending on the antibody employed. RT-PCR should be further investigated to measure PD-L1 expression, since it is a semi-quantitative method with observer-independent evaluation. With this approach, there was no statistical significant difference in the PD-L1 expression between responders and non-responders to the therapy with ipilimumab.