PD-L1 expression testing is mandatory prior to pembrolizumab prescription in non-small cell lung cancer. Pembrolizumab was made available in the UK through the Early Access to Medicines Scheme (EAMS) in May 2016 and was NICE-approved in December 2016. Our Molecular Pathology Diagnostic Service has been offering PD-L1 testing using Dako’s 22C3 IHC assay in parallel with EGFR and ALK testing. We present here data on the relationships between PD-L1 expression, and EGFR and ALK status in a series of 982 tumours.
PD-L1 expression testing was performed using the aforementioned assay on the 4800 Dako stainer. EGFR mutation testing was performed using the Therascreen kit on the RGQ platform and using COBAS kit (both screening for exon 19 deletions, L858R, G719X, L861Q, S768I, exon 20 insertions and T790M); ALK translocation was assessed using the D5F3 Ventana antibody on XT platform. PD-L1 was considered positive when more than 1% of tumour cells showed membranous staining.
Of the 982 tumours, 492 were positive for PD-L1 (50.1%), 85 bore EGFR mutations (8.7%) and 14 bore ALK translocations (1.4%). There was no significant difference in PD-L1 expression rate with EGFR mutation status. However, whereas 39.3% tumours with a classical EGFR mutation were PD-L1 positive, 86.4% with a rare EGFR mutation (G719X, L861Q, S768I, exon 20 insertions) were PD-L1 positive (p = 0.0006). PD-L1 positivity rate was 52.3% and 85.7% in ALK non-rearranged and rearranged tumours, respectively (p = 0.01).
Our data show that the presence of classical or of rare EGFR mutations is associated with different degrees of PD-L1 expression, which may have future therapeutic implications. Our data also show that the presence of an ALK translocation is positively associated with PD-L1 expression.
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All authors have declared no conflicts of interest.