Total neoadjuvant approach with FOLFOXIRI plus bevacizumab followed by chemoradiotherapy plus bevacizumab in locally advanced rectal cancer: the TRUST trial

Gianluca Masi, Caterina Vivaldi, Lorenzo Fornaro, Sara Lonardi, Piero Buccianti, Aldo Sainato, Lorenzo Marcucci, Angelo Martignetti, Emanuele Damiano Luca Urso, Maura Castagna, Gabriella Fontanini, Francesca Bergamo, Gianna Musettini, Lucio Urbani, Elisa Sensi, Riccardo Balestri, Sabrina Montrone, Francesco Pasqualetti, Chiara Cremolini, Antonello Di PaoloVittorina Zagonel, Alfredo Falcone

Research output: Contribution to journalArticle

Abstract

BACKGROUND: Neoadjuvant chemoradiotherapy (CRT) in locally advanced rectal cancer (LARC) does not achieve effective control of distant metastases. Induction chemotherapy is a promising strategy, and bevacizumab (BV) could improve the results of CRT. 5-Fluorouracil, oxaliplatin and irinotecan (FOLFOXIRI) plus BV is a treatment option in metastatic colorectal cancer. We evaluate feasibility and efficacy of neoadjuvant treatment comprising induction FOLFOXIRI plus BV followed by CRT with fluoropyrimidines plus BV.

METHODS: In this phase II single-arm trial, patients node-positive or clinical T4 or high-risk T3 LARC underwent 6 cycles of induction FOLFOXIRI plus BV, followed by CRT (50.4 Gy plus concomitant capecitabine) and BV (5 mg/kg on days 1, 15 and 28). Surgery was planned 8 weeks after completion of CRT. Primary end-point was 2-year disease-free survival (DFS).

RESULTS: We enrolled 49 patients: All but one (withdrewing consent after enrolment) were included in the per-protocol analyses. The study met its primary end-point: 36 patients were free of recurrence at 2 years (2-y DFS: 80.45%, 95% confidence interval [CI]: 78.79-82.10). Forty-four patients underwent surgery; pathologic complete response rate was 36.4%. Forty-six patients completed induction: neutropenia (41.6%) and diarrhoea (12.5%) were main G3/4 toxicities. Forty-five patients received CRT, but the protocol was amended and the capecitabine schedule during CRT was slightly modified after 13 patients due to the incidence of G3 hand-foot syndrome and proctitis (23.1%). After amendment, no severe events during CRT were reported.

CONCLUSIONS: FOLFOXIRI plus BV followed by CRT plus BV is feasible and active. Results in terms of DFS suggest that this strategy may improve distant disease control in LARC.

Original languageEnglish
Pages (from-to)32-41
Number of pages10
JournalEur. J. Cancer
Volume110
DOIs
Publication statusPublished - Mar 2019

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    Masi, G., Vivaldi, C., Fornaro, L., Lonardi, S., Buccianti, P., Sainato, A., Marcucci, L., Martignetti, A., Luca Urso, E. D., Castagna, M., Fontanini, G., Bergamo, F., Musettini, G., Urbani, L., Sensi, E., Balestri, R., Montrone, S., Pasqualetti, F., Cremolini, C., ... Falcone, A. (2019). Total neoadjuvant approach with FOLFOXIRI plus bevacizumab followed by chemoradiotherapy plus bevacizumab in locally advanced rectal cancer: the TRUST trial. Eur. J. Cancer, 110, 32-41. https://doi.org/10.1016/j.ejca.2019.01.006