Longitudinal analysis of PD-L1 expression in patients with relapsed NSCLC

Abstract

Background: The use and approval of immune checkpoint inhibitors for the treatment of non-small cell lung cancer (NSCLC) depends on PD-L1 expression in the tumor tissue. Nevertheless, PD-L1 often fails to predict response to treatment. One possible explanation could be a change in PD-L1 expression during the course of the disease and the neglect of reassessment. The purpose of this study was a longitudinal analysis of PD-L1 expression in patients with relapsed NSCLC.

Methods: We retrospectively analyzed PD-L1 expression in patients with early-stage NSCLC and subsequent relapse in preoperative samples, matched surgical specimens and biopsy samples of disease recurrence. Ventana PD-L1 (SP263) immunohistochemistry assay was used for all samples. PD-L1 expression was scored based on clinically relevant groups (0%, 1%-49%, and ≥50%). The primary endpoint was the change in PD-L1 score group between preoperative samples, matched surgical specimens and relapsed tumor tissue.

Results: 395 consecutive patients with stages I-III NSCLC and 136 (34%) patients with a subsequent relapse were identified. For 87 patients at least two specimens for comparison of PD-L1 expression between early stage and relapsed disease were available. In 72 cases, a longitudinal analysis between preoperative biopsy, the surgically resected specimen and biopsy of disease recurrence was feasible. When comparing preoperative and matched surgical specimens, a treatment-relevant conversion of PD-L1 expression group was found in 25 patients (34.7%). Neoadjuvant treatment showed no significant effect on PD-L1 alteration (p=0.39). In 32 (36.8%) out of 87 cases, a change in PD-L1 group was observed when biopsies of disease relapse were compared with early-stage disease. Adjuvant treatment was not significantly associated with a change in PD-L1 expression (p=0.53). 39 patients (54.2%) showed at least 1 change into a different PD-L1 score group during the course of disease. 14 patients (19.4%) changed the PD-L1 score group twice, 5 (6.9%) of them being found in all different score groups.

Conclusion: PD-L1 expression shows dynamic changes during the course of disease. There is an urgent need for consensus guidelines to define a PD-L1 testing strategy including time points of reassessment, the number of biopsies to be obtained and judgment of surgical specimens.

Keywords: Biomarker; Immune Checkpoint Inhibitor; Lung Cancer.

Figure 1

Consolidated Standards of Reporting Trials diagram and study design. NSCLC, non-small cell lung cancer.

Figure 2

PD-L1 change of all matched samples (N=72). PD-L1 expression (TPS) in biopsy samples, surgical specimens, and rebiopsy was compared. Each line represents one patient. Green lines represent patients who stayed within in the same PD-L1 score group, red lines represent patients who changed the PD-L1 score group at least one time during the course of disease. TPS, Tumor Proportion Scores.

Figure 3

Association between an absolute percentage change in PD-L1 expression of ≤10 or >10% with a change in PD-L1 score group.

Figure 4

Heterogeneity of PD-L1 expression in the same tumor: tumor proportion scores ranging from 100% (A), over 20 (B) to <1% (C).