Early-treatment coagulation activation and radiographic progression during VEGF/VEGFR inhibitor therapy: A multicancer real-world cohort study

Coagulation activation is common in cancer, but its link to treatment durability is unclear. We investigated whether early-treatment coagulation activation correlated with radiographic progression during vascular endothelial growth factor (VEGF)/vascular endothelial growth factor receptor (VEGFR) inhibitor therapy. This single-center, retrospective, multicancer cohort study developed a coagulation activation score (0-2) based on the last available D-dimer (>500 ng/mL) and fibrinogen (>4.0 g/L) measurements taken within 100 days after baseline. Multivariable Cox models calculated hazard ratios (HRs) and 95% confidence intervals (CIs) for subsequent radiographic time to progression among patients who were progression-free at the 100-day landmark. Of 1400 eligible patients, 1089 had evaluable early-treatment measurements, and 909 were included in the landmark analysis. Compared to a score of 0, adjusted HRs were 1.29 (95% CI 1.02-1.62) for score 1 and 1.51 (95% CI 1.07-2.12) for score 2. Score 2 also correlated with lower odds of durable clinical benefit (adjusted odds ratio 0.56, 95% CI 0.38-0.84), while objective response and best tumor shrinkage did not show a consistent gradient. These associations remained significant in time-dependent and timing-restricted analyses. Exploratory subgroup analyses revealed the strongest association in colorectal cancer patients treated with bevacizumab (score 2 vs. 0: HR 2.23, 95% CI 1.21-4.11); however, no association was observed in lung cancer patients treated with bevacizumab. No significant interaction with documented immune checkpoint inhibitor exposure was detected. The score did not enhance discrimination beyond clinical variables and baseline coagulation markers. Early-treatment coagulation activation was associated with reduced treatment durability during VEGF/VEGFR inhibition. Prospective validation in specific cancer-drug contexts is necessary.