Serum LDH predicts benefit from bevacizumab beyond progression in metastatic colorectal cancer

Br J Cancer. 2017 Jan;116(3):318-323. doi: 10.1038/bjc.2016.413. Epub 2017 Jan 12.

Abstract

Background: Different antiangiogenics are currently indicated in the second-line treatment of metastatic colorectal cancer (mCRC), following a first-line bevacizumab-containing treatment. The magnitude of benefit is limited, but no predictors of benefit have been identified.

Methods: A total of 184 mCRC patients progressing to a first-line bevacizumab-containing treatment were randomised in the BEBYP study to continue or not the antiangiogenic in combination with a second-line chemotherapy. A subgroup analysis according to baseline serum lactate dehydrogenase (LDH) levels was carried out.

Results: A significant interaction effect between LDH levels and treatment was found in terms of progression-free survival (PFS; P=0.002). Although patients with low LDH levels achieved significant PFS benefit from the continuation of bevacizumab (HR: 0.39 (95% CI: 0.23-0.65)), patients with high levels did not (HR: 1.10 (95% CI: 0.74-1.64)). Consistent results were reported in overall survival (OS; P=0.075).

Conclusions: As preclinical evidence suggests that serum LDH may be a marker of tumour angiogenesis activation, low levels may indicate that bevacizumab is still efficacious in inhibiting angiogenesis. Validation of present results in subgroup analyses of other randomised trials of second-line angiogenesis inhibitors is warranted.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / pathology
  • Adult
  • Aged
  • Angiogenesis Inhibitors / therapeutic use*
  • Bevacizumab / therapeutic use*
  • Biomarkers, Tumor / blood
  • Chemotherapy, Adjuvant
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / pathology
  • Disease Progression
  • Female
  • Humans
  • L-Lactate Dehydrogenase / blood*
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Prognosis
  • Treatment Outcome

Substances

  • Angiogenesis Inhibitors
  • Biomarkers, Tumor
  • Bevacizumab
  • L-Lactate Dehydrogenase