Effect of Platinum-Based Chemotherapy on PD-L1 Expression on Tumor Cells in Non-small Cell Lung Cancer

Abstract

Purpose: Programmed death-1 (PD-1)/PD-1 ligand (PD-L1) axis blockades have revolutionized the treatment of advanced non-small cell lung cancer (NSCLC). We assessed the effect of platinum-based chemotherapy on tumor PD-L1 expression and its clinical implications.

Materials and methods: We used immunohistochemistry to retrospectively evaluate the percentage of tumor cells with membranous PD-L1 staining (tumor proportion score) in paired tumor specimens obtained before and after platinum-based neoadjuvant chemotherapy (NACT) in 86 patients with NSCLC. We analyzed the correlation between the change in PD-L1 tumor proportion score and clinicopathologic characteristics, response to NACT, and survival.

Results: The PD-L1 tumor proportion score increased in a significant proportion of patients with NSCLC after platinum-based NACT (Wilcoxon signed-rank test, p=0.002). That pattern was consistent across clinically defined subgroups except for patients with partial response to NACT. Tumors from 26 patients (30.2%) were PD-L1‒negative before NACT but PD-L1-positive after NACT, whereas the reverse pattern occurred in six patients (7%) (McNemar's test, p < 0.001). Increase in PD-L1 tumor proportion score was significantly associated with lack of response to NACT (Fisher exact test, p=0.015). There was a tendency, albeit not statistically significant, for patients with an increase in PD-L1 tumor proportion score to have shorter survival.

Conclusion: Tumor PD-L1 expression increased after platinum-based NACT in a significant proportion of patients with NSCLC. Increase in tumor PD-L1 expression may predict poor clinical outcome.

Keywords: Neoadjuvant therapy; Non-small cell lung carcinoma; PD-L1; Platinum; Prognosis.

Fig. 1.

Flow diagram of patient selection. NSCLC, non-small cell lung cancer; NACT, neoadjuvant chemotherapy; SNUBH, Seoul National University Bundang Hospital; IHC, immunohistochemistry; PD-L1, programmed death ligand 1.

Fig. 2.

Distribution of programmed death ligand 1 (PD-L1) tumor proportion score before and after neoadjuvant chemotherapy (NACT) in the landmark analysis cohort (A). Subgroup analyses of males (B), females (C), never-smokers (D), current or former smokers (E), adenocarcinoma (F), squamous cell carcinoma (G), patients who received NACT without radiotherapy (H), gemcitabine-platinum (I), taxane-platinum (J), patients with partial response to NACT (K), and patients with stable disease (L). Numbers in bar plots indicate the number of patients included in each PD-L1 tumor proportion score category.

Fig. 3.

Representative immunohistochemical staining patterns of programmed death ligand 1 (PD-L1) in tumor specimens. (A, D) PD-L1 tumor proportion score ≥ 50% before (A) and after (D) neoadjuvant chemotherapy (NACT). (B, E) PD-L1 tumor proportion score ≥ 50% before (B) and < 1% after (E) NACT. (C, F) PD-L1 tumor proportion score < 1% before (C) and ≥ 50% after (F) NACT (A-F, ×200).

Fig. 4.

Disease-free survival (A) and overall survival (B) according to the direction of change in programmed death ligand 1 (PD-L1) tumor proportion score following platinum-based neoadjuvant chemotherapy (NACT). HR, hazard ratio; CI, confidence interval.

Fig. 5.

Subgroup analyses of the prognostic value of increased (versus unchanged or decreased) programmed death ligand 1 tumor proportion score following platinum-based neoadjuvant chemotherapy (NACT) for disease-free survival (A) and overall survival (B). Note that subgroups with less than 10 patients are omitted. The vertical dashed line indicates the hazard ratio (HR) for all patients in the survival analysis cohort. CI, confidence interval; PR, partial response; SD, stable disease.