560P - Impact of pre-treatment lactate dehydrogenase (LDH) levels on prognosis and bevacizumab efficacy in advanced colorectal cancer patients

Date 29 September 2014
Event ESMO 2014
Session Poster Display session
Topics Anti-Cancer Agents & Biologic Therapy
Colon Cancer
Rectal Cancer
Presenter Alessandro Passardi
Citation Annals of Oncology (2014) 25 (suppl_4): iv167-iv209. 10.1093/annonc/mdu333
Authors A. Passardi1, A. Farolfi1, O. Nanni1, D. Tassinari2, D. Turci3, L. Cavanna4, A. Fontana5, S. Ruscelli1, C. Mucciarini6, V. Lorusso7, A. Ragazzini1, D. Amadori1
  • 1Medical Oncology, IRCCS Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (I.R.S.T.), 47014 - Meldola/IT
  • 2Oncology, Ospedale Infermi, 47900 - Rimini/IT
  • 3Oncology, Ospedale Sta Maria delle Croci, IT-48400 - Ravenna/IT
  • 4Oncology Hematology Department, Azienda Ospedaliera Piacenza, IT-29121 - Piacenza/IT
  • 5Oncology Unit, University Hospital of Modena and Reggio Emilia, Modena/IT
  • 6U.o. Medicina Oncologica, Ospedale Ramazzini, Carpi/IT
  • 7Medical Oncology Unit, Ospedale Vito Fazzi, 73100 - Lecce/IT

Abstract

Aim

As LDH and pro-angiogenesis factors are regulated by the same HIF1α-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 < ULN 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 < ULN 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.