Perioperative Bevacizumab-based Triplet Chemotherapy in Patients With Potentially Resectable Colorectal Cancer Liver Metastases

Filippo Pietrantonio, Christian Cotsoglou, Giovanni Fucà, Salvatore Lo Vullo, Federico Nichetti, Massimo Milione, Jorgelina Coppa, Marta Vaiani, Alessandra Alessi, Michele Prisciandaro, Michele Droz-Dit Busset, Federica Morano, Salvatore Corallo, Silvia Lazzati, Maria Antista, Alessia Mennitto, Giovanni Randon, Alessandra Raimondi, Antonino Belfiore, Barbara PadovanoFederica Perrone, Luigi Mariani, Maria Di Bartolomeo, Filippo de Braud, Vincenzo Mazzaferro

Research output: Contribution to journalArticlepeer-review


Neoadjuvant triplet chemotherapy plus bevacizumab achieved pathologic response in 63% of colorectal cancer liver metastases. Early tumor shrinkage and posttreatment positron emission tomography predicted pathologic findings. Background: In colorectal cancer liver metastases (CRCLM), bevacizumab-based neoadjuvant strategies provide increased pathologic response. We aimed at assessing the activity of perioperative capecitabine, oxaliplatin, irinotecan, and bevacizumab (COI-B regimen) in patients with potentially resectable CRCLM, and investigating biomarkers for early prediction of pathologic response. Patients and Methods: This was a single-center phase II study enrolling patients with liver-limited, borderline resectable disease and/or high-risk features. Patients received 5 preoperative and 4 postoperative cycles of biweekly COI-B (irinotecan 180 mg/m 2 and bevacizumab 5 mg/Kg on day 1, oxaliplatin 85 mg/m 2 on day 2, and capecitabine 1000 mg/m 2 twice a day on days 2 to 6). The primary endpoint was pathologic response rate in the intention-to-treat population. A Simon 2-stage design was adopted to detect an increase from 30% to 50% with a power of 90%. Dynamic imaging biomarkers (early tumor shrinkage [ETS], deepness of response, maximum standardized uptake volume [SUVmax]/regression index) and next generation sequencing data were explored as surrogates. Results: From June 2013 to March 2017, 46 patients were enrolled. Pathologic response was achieved in 63% patients (endpoint met), and responders achieved significantly better survival outcomes with respect to non-responders. The most frequent grade 3/4 adverse events were diarrhea and neutropenia (8.7%) in the preoperative phase and thromboembolic events (5.9%) in the postoperative phase. ETS and lower SUV-2 were significantly associated with pathologic response. Conclusion: The COI-B regimen is a feasible and highly active perioperative strategy in patients with molecularly unselected, potentially resectable CRCLM. ETS and SUV-2 have a promising role as imaging-based biomarkers for pathologic response.

Original languageEnglish
Pages (from-to)34-43.e6
JournalClinical Colorectal Cancer
Issue number1
Publication statusPublished - Mar 2019


  • Colorectal cancer liver metastases
  • Pathologic response
  • Triplet chemotherapy
  • Tumor regression grade

ASJC Scopus subject areas

  • Oncology
  • Gastroenterology


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