560P - Impact of Pre-Treatment Lactate Dehydrogenase (Ldh) Levels on Prognosis and Bevacizumab Efficacy in Advanced Colorectal Cancer Patients

Abstract

ABSTRACT Aim: As LDH and pro-angiogenesis factors are regulated by the same HIF1a-driven pathway, high lactate dehydrogenase (LDH) levels are associated with abnormal activation of the VEGF pathway. We assessed the impact of pretreatment LDH levels on the prognosis of advanced colorectal cancer (ACC) patients treated with first-line chemotherapy with or without the anti-VEGF monoclonal antibody, bevacizumab, in a phase 3 randomized trial (NCT01878422). Methods: The relationship between pre-treatment LDH and progression free (PFS) and overall survival (OS) was assessed in 376 patients randomized to receive FOLFOX4 or FOLFIRI with or without bevacizumab. PFS, OS and their 95% confidence intervals (95% CI) were calculated by the Kaplan-Meier method. Results: Information on pre-treatment LDH levels was available for 344 ACC patients; 119 had normal LDH values and 225 had an LDH above the upper limit of the normal range (abnormal LDH). At a median follow up of 36 months (range 1-65), abnormal LDH levels were predictive of a lower median PFS (8.3 months, 95% CI 7.1-8.9 versus 9.8 months, 95% CI 9.1-10.9, p= 0.003) and median OS (19.2 months, 95% CI 16.3-21.1 versus 28.0 months, 95% CI 21.4-36.6, p= 0.0003). In the bevacizumab arm, median PFS was 9.1 (95% CI 7.8-10.2) and 9.7 (95% CI 7.4-12.2) months in patients with abnormal LDH and normal LDH, respectively (p = 0.308), whereas in the chemotherapy-only arm median PFS was 7.2 (95% CI 6.5-8.5) and 9.8 (95% CI 8.9-11.5) months, respectively (p = 0.002). Median OS was significantly associated with LDH levels in both treatment arms. Chemotherapy + bevacizumab Chemotherapy Pre-treatment LDH No. of patients No. of events Median PFS (95% CI) No. of patients No. of events Median PFS (95% CI) p LDH 62 53 9.7 (7.4-12.2) 57 51 9.8 (8.9-11.5) 0.522 LDH ≥ ULN 101 98 9.1 (7.8-10.2) 124 118 7.2 (6.5-8.5) 0.108 p 0.308 0.002 Pre-treatment LDH No. of patients No. of events Median OS (95% CI) No. of patients No. of events Median OS (95% CI) p LDH 62 36 28.0 (17.8-37.6) 57 35 28.6 (21.3-38.7) 0.444 LDH ≥ ULN 101 85 15.8 (13.1-21.1) 124 101 20.2 (17.9-23.2) 0.282 p 0.015 0.007 ULN, upper limit of normal Conclusions: In our study abnormal LDH values were correlated with worse prognosis. Bevacizumab appeared to improve the PFS of this population, but not the OS. Disclosure: All authors have declared no conflicts of interest.