A decrease in D-dimer concentration and an occurrence of skin rash as iatrogenic events and complementary predictors of survival in lung cancer patients treated with EGFR tyrosine kinase inhibitors.

BACKGROUND

Progression of lung cancer is associated with some abnormalities in coagulation. The aim of the study was to determine the predictive and prognostic value of changes in D-dimer concentration in non-small cell lung cancer (NSCLC) patients on anti-EGFR targeted therapy.

METHODS

The analysis included fifty two NSCLC patients treated with EGFR tyrosine kinase inhibitors (TKIs): erlotinib or gefitinib. All clinical data were collected before treatment and after 2 cycles (60days) of therapy and correlated with progression free and overall survival (PFS, OS).

RESULTS

Two iatrogenic events were noted within the first 60days of anti-EGFR treatment: typical skin rash in 38 (73.1%) and a decrease in D-dimer concentration in 26 (50%) patients. Multivariate analysis revealed a decrease of D-dimer concentration as the strongest factor associated with longer PFS (HR=0.39; 95%CI: 0.16-0.91; p=0.029) and OS (HR=0.33; 95%CI: 0.13-0.82, p=0.017) independently of skin rash, baseline level of D-dimer and other clinical characteristics. Coexisting a decrease in D-dimer concentration with an occurrence of skin rash correlated significantly with the positive objective response after 60days of anti-EGFR therapy (p=0.0175) and indicated the longest PFS (HR=0.31; 95%CI: 0.16-0.60, p=0.0005) as well as OS (HR=0.30; 95%CI: 0.15-0.59, p=0.0005).

CONCLUSIONS

Adverse events may predict the outcomes of cancer patients. Apart from skin rash, change in D-dimer concentration may be valuable parameter in creation of predictive and prognostic models in NSCLC patients receiving anti-EGFR targeted therapy.