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

Federica Marmorino, Lisa Salvatore, Cecilia Barbara, Giacomo Allegrini, Lorenzo Antonuzzo, Gianluca Masi, Fotios Loupakis, Beatrice Borelli, Silvana Chiara, Maria Chiara Banzi, Emanuela Miraglio, Domenico Amoroso, Francesco Dargenio, Andrea Bonetti, Angelo Martignetti, Myriam Paris, Daniela Tomcikova, Luca Boni, Alfredo Falcone, Chiara Cremolini

Research output: Contribution to journalArticle

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.
Original languageEnglish
Pages (from-to)318-323
Number of pages6
JournalBritish Journal of Cancer
Volume116
Issue number3
DOIs
Publication statusPublished - Jan 2017

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Keywords

  • Adenocarcinoma
  • Adult
  • Aged
  • Angiogenesis Inhibitors
  • Bevacizumab
  • Biomarkers, Tumor
  • Chemotherapy, Adjuvant
  • Colorectal Neoplasms
  • Disease Progression
  • Female
  • Humans
  • L-Lactate Dehydrogenase
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Prognosis
  • Treatment Outcome
  • Clinical Trial, Phase III
  • Journal Article
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

Cite this

Marmorino, F., Salvatore, L., Barbara, C., Allegrini, G., Antonuzzo, L., Masi, G., Loupakis, F., Borelli, B., Chiara, S., Banzi, M. C., Miraglio, E., Amoroso, D., Dargenio, F., Bonetti, A., Martignetti, A., Paris, M., Tomcikova, D., Boni, L., Falcone, A., & Cremolini, C. (2017). Serum LDH predicts benefit from bevacizumab beyond progression in metastatic colorectal cancer. British Journal of Cancer, 116(3), 318-323. https://doi.org/10.1038/bjc.2016.413