Association of baseline plasma D-dimer and platelets with progression-free survival in patients with stage IV non-small cell lung cancer treated with anti-PD-1 antibody

Background: In past studies, peripheral blood D-dimer and platelets have shown predictive value in the treatment of non-small cell lung cancer (NSCLC). However, it remains unclear whether pretreatment D-dimer and platelets can serve as biomarkers for predicting efficacy and prognosis in stage IV NSCLC patients without driver gene mutations receiving programmed cell death protein 1 (PD-1) antibody. Therefore, this study aims to investigate the correlation between baseline D-dimer and platelet levels and the efficacy and prognosis in the study population, aiding in determining the significance of baseline D-dimer and platelet levels as biomarkers.

Methods: This study included 150 patients who were newly diagnosed with stage IV NSCLC without driver gene mutations and conducted a retrospective analysis. Among them, 100 patients received first-line treatment with anti-PD-1 plus chemotherapy, while 50 patients received chemotherapy alone (2:1). Basic and clinical information for all patients was collected before treatment. Firstly, the differences in progression-free survival (PFS) and objective response rate (ORR) between the two treatment regimens were compared. Subsequently, the anti-PD-1 plus chemotherapy group and chemotherapy-alone group were analyzed separately, dividing patients into pretreatment high and low D-dimer group, as well as pretreatment high and low platelet group. Kaplan-Meier analysis and Cox proportional hazards models were used to analyze PFS data. Chi-squared tests and logistic regression analysis were employed to evaluate treatment efficacy, specifically ORR differences. All patients were followed up through electronic medical records and telephone, and disease assessment was conducted via imaging examinations, with the follow-up deadline being May 19, 2024.

Results: Kaplan-Meier analysis demonstrated that patients receiving anti-PD-1 plus chemotherapy had longer PFS compared to those receiving chemotherapy alone (median, 8.5 versus 5.5 months; P<0.001). Multivariate Cox regression analysis revealed that first-line chemotherapy (P<0.001), high baseline D-dimer level (P=0.002) and platelet count (P=0.04) were independent risk factors for shorter PFS. Pearson's Chi-squared test showed that the ORR was 46.00% for the anti-PD-1 plus chemotherapy group and 14.00% for the chemotherapy group (P<0.001). In the anti-PD-1 plus chemotherapy group, patients with low baseline D-dimer levels had longer PFS compared to those with high D-dimer level (median, 13.0 versus 8.0 months; P=0.005). Similar results were observed for baseline platelet count (median, 9.5 versus 6.5 months; P=0.005). In this group, no statistically significant differences were found in ORR between high and low D-dimer subgroups or high and low platelet subgroups (P=0.51 for D-dimer subgroups, P=0.87 for platelet subgroups). In the chemotherapy group, no correlation was observed between baseline D-dimer or platelet levels and PFS or ORR.

Conclusions: Pretreatment plasma D-dimer and platelet levels could serve as convenient prognostic biomarkers for stage IV NSCLC patients without driver gene mutations receiving anti-PD-1 antibody. Patients with higher baseline D-dimer and platelet levels might have poor PFS.