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S122 Relationship of PDL1 histological findings to prognosis and immunotherapy response in NSCLC: a systematic review

Introduction/Objectives Therapies targeting Programmed Death 1 (PD1) or its ligand (PDL1) are licensed for the management of advanced non-small cell lung cancer (NSCLC), and are currently recommended according to baseline tumour PDL1 expression. However, biopsy sampling biases and inconsistent correlation with patient outcomes suggest this biomarker may be unreliable, thus preventing patients likely to benefit from receiving this therapy. Therefore, we sought to determine the correlation between PDL1 expression and risk of death among patients with NSCLC receiving PD1 and PDL1 immunotherapy and identify alternative correlates of effectiveness. Methods In this systematic review, six databases were searched for randomised controlled trials (RCTs) and observational studies investigating nivolumab, pembrolizumab, atezolizumab or durvalumab. Study selection was performed independently by two reviewers. In this secondary analysis, risk of death pertaining to any reported baseline characteristic was analysed both by meta-analysis and descriptively. The primary results pertaining to treatment efficacy are reported separately. Results 39 studies were included. In 24 of these studies, PDL1 tumour proportion score (TPS) had an unclear relationship with risk of death. Among RCTs, patients with a PDL1 TPS ≥10% or ≥50% had a lower risk of death than patients with PDL1 TPS Additional factors correlating with risk of death included presence of metastases, EGFR mutation status, ECOG performance status (PS) and the neutrophil-to-lymphocyte ratio (NLR) (Table 1). Unlike the RCTs, numerous real-world studies found patients with metastases had a significantly higher risk of death. In RCTs, EGFR wildtype patients had a lower risk of death. In observational studies, a higher ECOG PS and NLR were associated with a higher risk of death. Discussion Our results suggest the current PDL1 threshold for stratifying patients may be redundant. This is problematic because immunotherapy has potential to harm patients and is very costly. However, we also identified several additional correlates of effectiveness which may be better indicators of patient prognosis. Therefore, future research could apply these findings to local cohorts, to test more suitable ways to stratify patients to receive this therapy.