Association of PD-L1 expression with efficacy of alectinib in advanced NSCLC patients with ALK fusion

Area of Science:

• Oncology
• Molecular Biology
• Clinical Research

Background:

• Programmed cell death-ligand 1 (PD-L1) expression is a known biomarker for reduced efficacy of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in EGFR-mutated non-small cell lung cancer (NSCLC).
• The predictive role of PD-L1 expression for alectinib efficacy in anaplastic lymphoma kinase (ALK)-positive NSCLC remains uncertain.

Purpose of the Study:

• To investigate the association between PD-L1 expression levels and the efficacy of front-line alectinib treatment in patients with ALK-positive NSCLC.
• To determine if PD-L1 expression can serve as a predictive biomarker for alectinib response in this patient population.

Main Methods:

• Retrospective analysis of 56 advanced ALK-positive NSCLC patients treated with front-line alectinib.
• Baseline PD-L1 expression was assessed using immunohistochemistry (IHC).
• Patients were categorized based on PD-L1 tumor proportion score (TPS): negative, 1%-49%, and ≥50%.

Main Results:

• No statistically significant association was found between PD-L1 positivity and objective response rate (ORR) or progression-free survival (PFS) in patients treated with alectinib.
• ORR was 90.0% in PD-L1 negative patients versus 80.8% in PD-L1 positive patients (p=0.274).
• PFS showed no significant difference between PD-L1 expression groups (HR: 0.98, p=0.97), with a trend towards longer PFS in patients with high PD-L1 expression (TPS ≥50%).

Conclusions:

• PD-L1 expression may not be a reliable predictive biomarker for the efficacy of front-line alectinib in ALK-positive NSCLC patients.
• Further research is warranted to fully elucidate the role of PD-L1 in ALK-positive NSCLC treated with targeted therapies.