MS 18.04 PD-L1 Expression in Early Stage Lung Cancer

Abstract

The significant activity of programmed cell death 1 (PD-1)/PD-1 ligand 1 (PD-L1) checkpoint inhibitors in heavily pre-treated patients with advanced non–small-cell lung cancer (NSCLC) marked the beginning of a new era of immunotherapy. Recently published randomized clinical trials’ data have led to the approval of 3 PD-1/PD-L1 inhibitors—nivolumab (Opdivo; Bristol-Myers Squibb Company), pembrolizumab (Keytruda; Merck Sharp & Dohme Corp), and atezolizumab (Tecentriq, Genentech/Roche)—for the treatment of advanced NSCLC after first-line therapy. Furthermore, pembrolizumab was recently approved by the FDA as a first-line therapy for patients with advanced NSCLC. However, the overall response rates to these agents in an unselected population are reportedly low, thus emphasising the need for predictive biomarkers that identify beneficial candidates. The recently approved tests for anti-PD-1/PD-L1 therapy in NSCLC include the assessment of PD-L1 expression using immunohistochemistry (IHC) as a companion diagnostic test (22C3 for pembrolizumab) and 2 complementary diagnostic tests (28-8 for nivolumab and SP142 for atezolizumab). Another PD-L1 assay is being currently tested in clinical trials (e.g. SP263). In addition to commercial assays, laboratories and research institutions may establish their own laboratory-developed tests (LDTs) using various antibodies available, most notably the E1L3N clone. Hence, the PD-L1 expression status, as well as its predictive and prognostic value, differ considerably based on the antibody clones, platforms, and interpretation criteria used. However, the current assays evaluating the predictive role of tumor PD-L1 expression remain without harmonization in terms of the staining analysis and scoring system. The intratumoral heterogeneity in PD-L1 expression is another important issue. At present, PD-L1 testing is mainly conducted on biopsy specimens, which may not represent the tumor as a whole, and it may lead to false results, particularly in cases where testing is conducted using small tissue specimens, such as bronchial or transthoracic biopsy specimens. The resulting false-negative results could lead to the under-treatment of patients. In this presentation, I’d like to introduce 1) the results of comparison study between 4 different PD-L1 IHC and scoring systems in the surgically resected early stage lung cancer specimen 2) the correlation of PD-L1 expression between TMA specimens and the corresponding resected specimen to better understand the intratumoral heterogeneity. PD-L1, immunohistochemistry, lung cancer