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Pathological response after neoadjuvant bevacizumab- or cetuximab-based chemotherapy in resected colorectal cancer liver metastases

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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.

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Authors and Affiliations

  1. Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori (National Cancer Institute), Via Venezian, 1, 20133, Milan, Italy

    Filippo Pietrantonio, Giuseppe Fanetti, Pamela Biondani, Maria Di Bartolomeo, Claudia Maggi & Filippo de Braud

  2. Departments of Surgery, Liver Transplantation and Gastroenterology, Fondazione IRCCS Istituto Nazionale dei Tumori (National Cancer Institute), Milan, Italy

    Vincenzo Mazzaferro, Christian Cotsoglou, Cecilia Muscarà & Jorgelina Coppa

  3. Biomedical Statistics and Trial Office, Fondazione IRCCS Istituto Nazionale dei Tumori (National Cancer Institute), Milan, Italy

    Rosalba Miceli

  4. Department of Pathology, Azienda Ospedaliera di Desenzano del Garda, Desenzano del Garda, Italy

    Flavia Melotti

  5. Department of Pathology and Molecular Biology, Fondazione IRCCS Istituto Nazionale dei Tumori (National Cancer Institute), Milan, Italy

    Federica Perrone, Massimo Milione & Elena Tamborini

Authors
  1. Filippo Pietrantonio
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  2. Vincenzo Mazzaferro
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Correspondence to Filippo Pietrantonio or Vincenzo Mazzaferro.

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12032_2015_638_MOESM1_ESM.pptx

Distributions of three-category tumour regression grade (TRG) according to treatment group (bevacizumab- versus cetuximab-based neoadjuvant chemotherapy). TRG categories (TRG1–2: major-to-complete pathological response vs. TRG3: partial response vs. TRG4–5: no response) are shown as absolute percentages (bars). (PPTX 47 kb)

Supplementary material 2 (DOC 44 kb)

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Pietrantonio, F., Mazzaferro, V., Miceli, R. et al. Pathological response after neoadjuvant bevacizumab- or cetuximab-based chemotherapy in resected colorectal cancer liver metastases. Med Oncol 32, 182 (2015). https://doi.org/10.1007/s12032-015-0638-3

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  • DOI: https://doi.org/10.1007/s12032-015-0638-3

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