title: Pathological response after neoadjuvant bevacizumab- or cetuximab-based chemotherapy in resected colorectal cancer liver metastases.
abstract: Neoadjuvant chemotherapy (NACT) prior to liver resection is advantageous for patients with colorectal cancer liver metastases (CLM). Bevacizumab- or cetuximab-based NACT may affect patient outcome and curative resection rate, but comparative studies on differential tumour regression grade (TRG) associated with distinct antibodies-associated regimens are lacking. Ninety-three consecutive patients received NACT plus bevacizumab (n = 46) or cetuximab (n = 47) followed by CLM resection. Pathological response was determined in each resected metastasis as TRG rated from 1 (complete) to 5 (no response). Except for KRAS mutations prevailing in bevacizumab versus cetuximab (57 vs. 21 %, p = 0.001), patients characteristics were well balanced. Median follow-up was 31 months (IQR 17-48). Bevacizumab induced significantly better pathological response rates (TRG1-3: 78 vs. 34 %, p < 0.001) as well as complete responses (TRG1: 13 vs. 0 %, p = 0.012) with respect to cetuximab. Three-year progression-free survival (PFS) and overall survival (OS) were not significantly different in the two cohorts. At multivariable analysis, significant association with pathological response was found for number of resected metastases (p = 0.015) and bevacizumab allocation (p < 0.001), while KRAS mutation showed only a trend. Significant association with poorer PFS and OS was found for low grades of pathological response (p = 0.009 and p < 0.001, respectively), R2 resection or presence of extrahepatic disease (both p < 0.001) and presence of KRAS mutation (p = 0.007 and p < 0.001, respectively). Bevacizumab-based regimens, although influenced by the number of metastases and KRAS status, improve significantly pathological response if compared to cetuximab-based NACT. Possible differential impact among regimens on patient outcome has still to be elucidated.
authors.affiliation: Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori (National Cancer Institute), Via Venezian, 1, 20133, Milan, Italy, filippo.pietrantonio@istitutotumori.mi.it.
authors.forename: Filippo
authors.initials: F
authors.lastname: Pietrantonio
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Mazzaferro
authors.forename: Rosalba
authors.initials: R
authors.lastname: Miceli
authors.forename: Christian
authors.initials: C
authors.lastname: Cotsoglou
authors.forename: Flavia
authors.initials: F
authors.lastname: Melotti
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Fanetti
authors.forename: Federica
authors.initials: F
authors.lastname: Perrone
authors.forename: Pamela
authors.initials: P
authors.lastname: Biondani
authors.forename: Cecilia
authors.initials: C
authors.lastname: Muscarà
authors.forename: Maria
authors.initials: M
authors.lastname: Di Bartolomeo
authors.forename: Jorgelina
authors.initials: J
authors.lastname: Coppa
authors.forename: Claudia
authors.initials: C
authors.lastname: Maggi
authors.forename: Massimo
authors.initials: M
authors.lastname: Milione
authors.forename: Elena
authors.initials: E
authors.lastname: Tamborini
authors.forename: Filippo
authors.initials: F
authors.lastname: de Braud
mesh_terms: D000368:Aged; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D000068258:Bevacizumab / Q000627:therapeutic use*; D000068818:Cetuximab / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology* / Q000601:surgery; D018572:Disease-Free Survival; D005260:Female; D006498:Hepatectomy / Q000379:methods; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000473:pathology / Q000601:surgery; D008113:Liver Neoplasms / Q000235:genetics / Q000473:pathology* / Q000556:secondary / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D020360:Neoadjuvant Therapy / Q000379:methods; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics; D016896:Treatment Outcome
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; C117307:KRAS protein, human; D000068258:Bevacizumab; D016283:Proto-Oncogene Proteins p21(ras); D000068818:Cetuximab