PD-L1 expression in primary lung tumor as a superior predictive biomarker to metastatic lymph nodes for first-line immunochemotherapy in advanced KRAS-mutant non-small cell lung cancer.

Background: The correlation between programmed death-ligand 1 (PD-L1) expression and the efficacy of first-line chemoimmunotherapy in advanced KRAS-mutant non-small cell lung cancer (NSCLC) is inconsistent across studies, possibly due to the spatial heterogeneity of PD-L1 expression. We characterized the PD-L1 expression profile at different tumor sites and its impact on the clinical efficacy of first-line immunochemotherapy in advanced KRAS-mutant NSCLC patients. Methods: A retrospective analysis was performed on 302 patients with advanced KRAS-mutant NSCLC who received first-line immunochemotherapy from January 2018 to December 2022. Patients were categorized by biopsy sites: primary lung lesions (n=211) and metastatic lymph nodes (n=91). PD-L1 expression was stratified into <1%, 1-49%, and ≥50%. Primary endpoints included progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR). Results: Median PFS was 9.07 months overall, 7.27 months for PD-L1 <1%, 8.30 months for PD-L1 =1-49%, and 15.00 months for PD-L1 ≥50% (P<0.001). The corresponding median PFS values for patients with primary lung lesions were 7.23, 8.30, and 15.03 months, which were statistically significant (P=0.001). In contrast, no significant differences in PFS were observed among the PD-L1 subgroups for patients with metastatic lymph nodes (P=0.17). Moreover, the non-G12C subgroup exhibited a more pronounced PD-L1 expression heterogeneity between the primary and metastatic sites than the G12C subgroup. Conclusions: In advanced KRAS-mutant NSCLC, the PD-L1 expression in primary lung lesions may predict first-line immunochemotherapy efficacy, while PD-L1 expression in metastatic lymph nodes lacks predictive value, especially in non-G12C mutations.