Stratification of Non-Small-Cell Lung Cancer patients by PD-L1 Expression across Four NHS Trusts
Session type: E-poster/poster
Theme: Immunology and immunotherapy
In non-small-cell lung cancer (NSCLC), immunotherapy manipulates a checkpoint involving programmed death receptor 1 (PD-1) and programmed death ligand 1 (PD-L1). Response to PD-1 inhibitors may be predicted by PD-L1 expression of neoplastic cells. Pembrolizumab is used to treat NSCLC based on PD-L1 levels. PD-L1 assays were intially validated for histological specimens only, now there is evidence that cytology specimens are suitable. We stratified NSCLC patients using PD-L1 expression and evaluated expression in cytological specimens.
Stratification of patients tested for PD-L1 expression across four NHS trusts (Royal Devon and Exeter, North Devon, Torbay and South Devon, and Royal Cornwall NHS Trusts) was performed using DAKO PDL1 immunohistochemistry (IHC; 22C3 pharmDX); by percentage of tumour cells positive. Within the Royal Devon and Exeter Trust pathology reports were scrutinised for NSCLC subtype and speciment type for testing. In a further subset of these patients, notes and radiology revealed clinical response in a cohort receiving immunotherapy.
Between January 2017 and May 2019 483 PD-L1 assays were performed across the four NHS trusts, 172 (36%) were negative (<1% PD-L1 expression), 167 (35%) showed expression ≤49%, and 136 (28%) showed expression ≥50%. Eight tests contained insufficient cell populations to score PD-L1 expression. Within the Royal Devon and Exeter Trust, 101 assays on histological specimens showed 25 with ≥50% PD-L1 expression (25%), 72 with ≤49% (71%), and 4 insufficient samples (4%). The 60 cytological samples were comparable, 17 showing ≥50% (28%), 40 showing ≤49% (67%), and 3 insufficient samples (5%). Twenty two patients received immunotherapy as of November 2017, 16 had ≥50% expression, 6 patients showed expression between 5-49%. 9 patients demonstrated disease reduction, 5 stable disease, 8 no response.
The Keynote-024 trial demonstrated that in NSCLC patients with PD-L1 expression ≥50%, pembrolizumab improved progression-free and overall survival compared to chemotherapy. Stratification by PDL-1 expression in our cohort is consistent with previous literature. Studies with paired comparison of PD-L1 expression on cytological and histological specimens indicate feasibility of using cytological material alone, this is supported by our experience.
Demonstrating feasability of PD-L1 testing on cytology may preclude the need for biopsy in assessing suitablity for immunotherapy.