Elevated levels of pre-treatment lactate dehydrogenase are an unfavorable predictor factor in patients with EML4-ALK rearrangement non-small cell lung cancer treated with crizotinib

Abstract

Background: Targeted therapy is an important treatment for advanced non-small cell lung cancer (NSCLC) patients with specific genetic mutations, crizotinib can prolong survival in advanced NSCLC patients with echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) rearrangement. We performed a retrospective analysis to investigate the association between the lactate dehydrogenase (LDH) levels and progressionfree survival (PFS) in patients with EML4-ALK rearrangement NSCLC receiving treatment with crizotinib. Methods: Advanced (stage IIIb-IV) NSCLC patients with EML4-ALK rearrangement receiving treatment with crizotinib were enrolled between January 2007 and January 2016 at Peking Union Medical College and Cancer Hospital Chinese Academy of Medical Sciences. Results: Overall, 212 patients were enrolled. Kaplan-Meier univariate analysis showed that elevated pre-treatment LDH level (7.9 vs 14.1 months, HR =1.251, CI: 1.008-1.553, P=0.004) was significantly associated with shorter PFS, while the post-treatment mean- LDH level (13.3 vs 14.3 months, HR=1.439, 95% CI: 0.994-2.082, P=0.970) was not significantly associated with PFS. Cox proportional hazards model also identified that pretreatment LDH level (HR=2.085, 95% CI: 1.150-3.781, P=0.016) was associated with the PFS. Logistic regression analysis showed that post-treatment LDH level was associated with creatine kinase (OR=6.712, 95% CI 3.395-13.273, P<0.01), creatine kinase isoenzyme (OR=6.297, 95% CI 2.953-13.427, P<0.01), and hemoglobin (OR=4.163, 1.741-9.956, P<0.001). Conclusion: An elevated pre-treatment serum LDH level (>250 U/L) was significantly associated with shorter PFS in patients with EML4-ALK rearrangement NSCLC. Posttreatment elevated serum LDH level was not significantly associated with PFS, which related to adverse events including muscle damage and anemia.