PD-L1 expression in lung adenocarcinoma harboring EGFR mutations or ALK rearrangements

Highlights

• PD-L1 expression in NSCLC positive for known driver oncogenes has remained unclear.

• We measured PD-L1 TPS in patients with EGFR mutations or ALK rearrangements.

• 32.5% had a PD-L1 TPS of 1%–49% and 11.3% had a PD-L1 TPS of at least 50%.

• PFS on initial TKI was poorer for patients with a PD-L1 TPS of ≥1% than <1%.

Abstract

Objectives

Expression of programmed cell death–ligand 1 (PD-L1) has been associated with clinical outcome of programmed cell death–1 (PD-1) pathway blockade in non–small cell lung cancer (NSCLC). The PD-L1 IHC 22C3 pharmDx assay, the only companion diagnostic for pembrolizumab therapy, has revealed that ∼30% of all NSCLCs express PD-L1 at a high level. The frequency of high PD-L1 expression in NSCLCs with known driver oncogenes has remained unclear, however.

Materials and methods

We retrospectively evaluated PD-L1 expression with the 22C3 assay in tumor tissue of 80 lung adenocarcinoma patients including 71 with EGFR mutations and 9 with ALK rearrangements, all of whom were treated with corresponding tyrosine kinase inhibitors (TKIs).

Results

Of the 80 tumors analyzed, 26 (32.5%) had a PD-L1 tumor proportion score (TPS) of 1%–49% and 9 (11.3%) had a PD-L1 TPS of ≥50%; 35 (43.8%) thus had a PD-L1 TPS of ≥1%. Of the 71 tumors with EGFR mutations, 23 (32.4%) had a PD-L1 TPS of 1%–49% and 7 (9.9%) had a PD-L1 TPS of ≥50%. A PD-L1 TPS of ≥1% was not associated with any clinical characteristic examined. Progression-free survival on initial TKI treatment was significantly poorer for patients with a PD-L1 TPS of ≥1% than for those with a PD-L1 TPS of <1% (p = .016).

Conclusions

A subset of patients with EGFR mutations or ALK rearrangements had a PD-L1 TPS of ≥50%. Prospective studies are thus warranted to examine the efficacy of PD-1/PD-L1 inhibitors in such patients.

Introduction

Management of advanced non–small cell lung cancer (NSCLC) has improved profoundly in recent years as a result of rapid advances in our understanding of its genetic drivers [1]. The presence of epidermal growth factor receptor gene (EGFR) mutations, anaplastic lymphoma kinase gene (ALK) rearrangements, or ROS1 rearrangements is predictive of the therapeutic efficacy of corresponding oral tyrosine kinase inhibitors (TKIs), which are associated with more durable outcomes, less toxicity, and a better quality of life compared with conventional chemotherapy [[2], [3], [4]]. Immunotherapy is a new paradigm for the treatment of NSCLC, with immune-checkpoint inhibitors that target programmed cell death–1 (PD-1) or its ligand PD-L1 also conferring a survival benefit for patients with advanced disease when compared with conventional chemotherapy [[5], [6], [7], [8], [9]]. PD-L1 expression in tumor cells has been associated with an improved clinical outcome of PD-1 pathway blockade in NSCLC patients [[6], [10], [11]]. Although many antibodies are available for detection of PD-L1 expression by immunohistochemistry (IHC), the PD-L1 IHC 22C3 pharmDx assay is the only approved companion diagnostic for the treatment of NSCLC with the PD-1–targeted monoclonal antibody pembrolizumab.

On the basis of the results of the KEYNOTE-024 phase III trial, a randomized comparison of pembrolizumab versus platinum-based chemotherapy [8], pembrolizumab has become a standard option for first-line treatment of advanced NSCLC with a PD-L1 tumor proportion score (TPS) of at least 50%. Given that patients with EGFR mutations or ALK rearrangements were excluded from this study, the frequency of a high level of PD-L1 expression in NSCLC harboring these driver oncogenes has remained unclear. We have therefore now determined the PD-L1 TPS with the 22C3 pharmDx assay for lung adenocarcinoma patients with EGFR mutations or ALK rearrangements.