Investigation on the survival implications of PD-L1 expression status in ALK- rearranged advanced non-small cell lung cancer treated with first-line crizotinib

Abstract

Background: Programmed cell death-ligand 1 (PD-L1) expression has been associated with shorter progression-free survival (PFS) of crizotinib-treated patients with anaplastic lymphoma kinase (ALK) rearranged non-small cell lung cancer (NSCLC). However, the association between PD-L1 expression and overall survival (OS) in ALK-rearranged NSCLC remains unclear. In this study, we investigated the survival implication of baseline PD-L1 expression status in crizotinib-treated patients with ALK-rearranged advanced NSCLC.

Methods: Between October 1, 2015, and October 31, 2021, we retrospectively analyzed the baseline PD-L1 expression levels using immunohistochemistry 22C3 assay of tissue samples from 128 patients with ALK-rearranged advanced lung adenocarcinoma who were treated with first-line crizotinib.

Results: Of the 128 baseline tumor specimens analyzed, a majority (76.6%, n = 98) had low PD-L1 expression (tumor proportion score (TPS) < 50%), wherein 58.6% (n = 75) had < 1% and 18.0% (n = 23) had 1%-49%, and the remaining 23.4% (n = 30) had high PD-L1 expression level (TPS ≥ 50%). High baseline PD-L1 expression was not associated with any clinical characteristic examined. Patients with high baseline PD-L1 (n = 30) expression level had significantly shorter median PFS (6 vs 11 months, p = 0.011) and OS (17 vs 53 months, p = 0.023) on crizotinib treatment than those with low PD-L1 level (n = 98).

Conclusions: A subset of patients with ALK-rearranged NSCLC having high baseline PD-L1 expression level (TPS of ≥ 50%) had poorer survival outcomes despite crizotinib therapy. Our study raises the need to investigate alternative treatment strategies to improve survival outcomes of this patient subset.

Trial registration: ClinicalTrials.gov NCT03647111.

Keywords: ALK-rearranged NSCLC; Crizotinib; Overall Survival Time; PD-L1.