TRUST: Phase II trial of induction chemotherapy (CT) with FOLFOXIRI + bevacizumab (BV) followed by chemo-radiotherapy (CRT) + BV and surgery in locally advanced rectal carcinoma (LARC)

Background

Induction CT followed by CRT is a promising strategy in LARC. FOLFOXIRI + BV is an effective treatment in metastatic colorectal cancer.

Methods

This is a phase II single-arm trial. Patients (pts) with LARC at

Results

We enrolled 48 pts: median age, 53 years (30-74); cT2/T3/T4, 4%/60%/36%; cN0/N + , 4%/96%; distance from anal verge 0-5/5-10/ > 10 cm, 56%/38%/6%. 46 pts completed induction therapy; 2 pts prematurely stopped treatment: 1 bowel perforation and sepsis resulting in death and 1 acute kidney injury recovered without sequelae. Main grade (G) 3/4 toxicities were: neutropenia (42%), febrile neutropenia (4.2%) and diarrhea (12.5%). After induction therapy 45 pts started CRT and 1 underwent surgery. After the first 13 pts, the protocol was amended and the schedule of capecitabine slightly modified (800 mg/m²/bid 5 days/week) due to an excessive rate of G3 hand-foot syndrome (23%) and proctitis (23%). After amendment, all pts completed CRT with acceptable toxicity: no G3-4 toxicities were reported, with the exception of proctitis (6.2%). After CRT 44 pts underwent surgery (1 died due to early progression after CRT): low anterior (89%) or abdomino-perineal (7%) resection. R0 resection was achieved in 98% resected pts. Early post-surgical complication rate was 32%, with a rate of 18% of anastomotic dehiscences (all solved). Pathologic complete response (pCR) rate was 36%. At a median follow up of 25.1 months, 11 pts experienced disease progression (3 local recurrences) and the estimated 2-year DFS is 78.8%.

Conclusions

Induction therapy with FOLFOXIRI + BV followed by CRT + BV is feasible, but a careful patient selection is needed because of the overall safety profile. Results in terms of pCR and preliminary DFS data are promising.

Clinical trial identification

EUDRACT 2011-003340-45 Start Date: 2012-02-23

Legal entity responsible for the study

Fondazione ARCO Onlus

Funding

trial promoted by Fondazione ARCO Onlus, bevacizumab provided by Roche

Disclosure

A. Falcone: Honoraria, advisory role, speakers' bureau: Amgen, Bayer, Merck Serono, Roche, Sanofi, Lilly. Research funding: Amgen, Bayer, Merck Serono, Roche, Sanofi. G. Masi: Honoraria: Roche, Merck Serono, Amgen, Sirtex. All other authors have declared no conflicts of interest.