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.

Perioperative Bevacizumab-based Triplet Chemotherapy in Patients with Potentially Resectable Colorectal Cancer Liver Metastases / F. Pietrantonio, C. Cotsoglou, G. Fucà, S. Lo Vullo, F. Nichetti, M. Milione, J. Coppa, M. Vaiani, A. Alessi, M. Prisciandaro, M. Droz-Dit Busset, F. Morano, S. Corallo, S. Lazzat, M. Antista, A. Mennitto, G. Randon, A. Raimondi, A. Belfiore, B. Padovano, F. Perrone, L. Mariani, M. Di Bartolomeo, F. de Braud, V. Mazzaferro. - In: CLINICAL COLORECTAL CANCER. - ISSN 1533-0028. - 18:1(2019 Mar), pp. 34-43.e6. [10.1016/j.clcc.2018.11.004]

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

F. Pietrantonio;C. Cotsoglou;G. Fucà;F. Nichetti;J. Coppa;A. Alessi;M. Prisciandaro;M. Droz-Dit Busset;S. Corallo;A. Mennitto;G. Randon;A. Raimondi;B. Padovano;F. Perrone;M. Di Bartolomeo;F. de Braud;V. Mazzaferro
2019-03

Abstract

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.
colorectal cancer liver metastases; FGD-PET/CT; pathologic response; triplet chemotherapy; tumor regression grade;
Settore MED/06 - Oncologia Medica
Settore MED/18 - Chirurgia Generale
nov-2018
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/621890
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