title: Serum LDH predicts benefit from bevacizumab beyond progression in metastatic colorectal cancer.
abstract: 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.
  
  
  
  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.
  
  
  
  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).
  
  
  
  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.
authors.affiliation: Azienda Ospedaliero-Universitaria Pisana, University of Pisa, Istituto Toscano Tumori, Via Roma, 67, 56126 Pisa, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Marmorino
authors.affiliation: Azienda Ospedaliero-Universitaria Pisana, University of Pisa, Istituto Toscano Tumori, Via Roma, 67, 56126 Pisa, Italy.
authors.forename: Lisa
authors.initials: L
authors.lastname: Salvatore
authors.affiliation: Department of Medical Oncology, Ospedale Civile di Livorno, Viale Alfieri, 36, 57121 Livorno, Italy.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Barbara
authors.affiliation: Division of Medical Oncology, Pontedera Hospital, via Taddeo Alderotti, 26, 56025 Pisa, Italy.
authors.forename: Giacomo
authors.initials: G
authors.lastname: Allegrini
authors.affiliation: Azienda Ospedaliero-Universitaria Careggi, Largo Brambilla, 3, 50134 Firenze, Italy.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Antonuzzo
authors.affiliation: Azienda Ospedaliero-Universitaria Pisana, University of Pisa, Istituto Toscano Tumori, Via Roma, 67, 56126 Pisa, Italy.
authors.forename: Gianluca
authors.initials: G
authors.lastname: Masi
authors.affiliation: Istituto Oncologico Venoto, Via Gattamelata, 64, 35128 Padova, Italy.
authors.forename: Fotios
authors.initials: F
authors.lastname: Loupakis
authors.affiliation: Azienda Ospedaliero-Universitaria Pisana, University of Pisa, Istituto Toscano Tumori, Via Roma, 67, 56126 Pisa, Italy.
authors.forename: Beatrice
authors.initials: B
authors.lastname: Borelli
authors.affiliation: National Institute for Cancer Research, Largo R. Benzi, 10, 16132 Genova, Italy.
authors.forename: Silvana
authors.initials: S
authors.lastname: Chiara
authors.affiliation: Arcispedale Santa Maria Nuova, IRCCS, Viale Risorgimento, 80, 42123 Reggio Emilia, Italy.
authors.forename: Maria Chiara
authors.initials: MC
authors.lastname: Banzi
authors.affiliation: Department of Oncology, S. Croce General Hospital, Via Carle 25, 12100 Cuneo, Italy.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Miraglio
authors.affiliation: Ospedale Versilia-Lido di Camaiore, Strada Statale 1 Via Aurelia, 335, 55041 Viareggio, Italy.
authors.forename: Domenico
authors.initials: D
authors.lastname: Amoroso
authors.affiliation: Dipartimento oncologico AUSL 6 Livorno-Piombino, Via Forlanini, 57025 Piombino, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Dargenio
authors.affiliation: Department of Medical Oncology Mater Salutis Hospital Legnago, Via Gianella 1, 37045 Legnago, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Bonetti
authors.affiliation: Dipartimento Oncologico AUSL 7, Val d'Elsa, 53036 Poggibonsi, Italy.
authors.forename: Angelo
authors.initials: A
authors.lastname: Martignetti
authors.affiliation: S.O.C. Oncologia-Ospedale degli Infermi, Via Ponderanesi, 2, 13811 Biella, Italy.
authors.forename: Myriam
authors.initials: M
authors.lastname: Paris
authors.affiliation: Fondazione Sandro Pitigliani, Via Dolce de Mazzamuti, 7, 59100 Prato, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Tomcikova
authors.affiliation: Clinical Trial Coordinating Center, AOU Careggi, Istituto Toscano Tumori, Largo Brambilla, 3, 50134 Firenze, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Boni
authors.affiliation: Azienda Ospedaliero-Universitaria Pisana, University of Pisa, Istituto Toscano Tumori, Via Roma, 67, 56126 Pisa, Italy.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Falcone
authors.affiliation: Azienda Ospedaliero-Universitaria Pisana, University of Pisa, Istituto Toscano Tumori, Via Roma, 67, 56126 Pisa, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Cremolini
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000068258:Bevacizumab / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000097:blood; D017024:Chemotherapy, Adjuvant; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D018450:Disease Progression; D005260:Female; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011379:Prognosis; D016896:Treatment Outcome
chemical_list: D020533:Angiogenesis Inhibitors; D014408:Biomarkers, Tumor; D000068258:Bevacizumab; D007770:L-Lactate Dehydrogenase