BACCHUS: A randomised non-comparative phase II study of neoadjuvant chemotherapy (NACT) in patients with locally advanced rectal cancer (LARC)

Abstract

BackgroundChemoradiation (CRT) or short-course radiotherapy (SCRT) are standard treatments for locally advanced rectal cancer (LARC). We evaluated the efficacy/safety of two neoadjuvant chemotherapy (NACT) regimens as an alternative prior to total mesorectal excision (TME).Methods/designThis multi-centre, phase II trial in patients with magnetic resonance imaging (MRI) defined high-risk LARC (>cT3b, cN2+ or extramural venous invasion) randomised patients (1:1) to FOLFOX + Bevacizumab (Arm 1) or FOLFOXIRI + bevacizumab (Arm 2) every 14 days for 6 cycles prior to surgery. Patients were withdrawn if positron emission tomography (PET) standardised uptake value (SUV) after 3 cycles failed to decrease by >30% or increased compared to baseline. Primary endpoint was pathological complete response rate (pCR). Secondary endpoints included adverse events (AE) and toxicity. Neoadjuvant rectal (NAR) scores based on “T” and “N” downstaging were calculated.FindingsTwenty patients aged 18–75 years were randomised. The trial stopped early because of poor accrual. Seventeen patients completed all 6 cycles of NACT. One stopped due to myocardial infarction, 1 poor response on PET (both received CRT) and 1 committed suicide. 11 patients had G3 AE, 1 G4 AE (neutropenia), and 1 G5 (suicide). pCR (the primary endpoint) was 0/10 for Arm 1 and 2/10 for Arm 2 i.e. 2/20 (10%) overall. Median NAR score was 14·9 with 5 (28%), 7 (39%), and 6 (33%) having low, intermediate, or high scores. Surgical morbidity was acceptable (1/18 wound infection, no anastomotic leak/pelvic sepsis/fistulae). The 24-month progression-free survival rate was 75% (95% CI: 60%–85%).InterpretationThe primary endpoint (pCR rate) was not met. However, FOLFOXIRI and bevacizumab achieved promising pCR rates, low NAR scores and was well-tolerated. This regimen is suitable for testing as the novel arm against current standards of SCRT and/or CRT in a future trial.

Neoadjuvant rectal (NAR) score: Value evaluating the efficacy of neoadjuvant therapy and prognostic significance after surgery?

“…adding neoadjuvant chemotherapy to CRT [19] and in two studies where chemotherapy alone was used [20,21]. However, a recent study from the Netherlands dismissed the prognostic value of NAR-score; single pathological parameters (pT, pN) have similar concordance (C-index of 0.663 and 0.655), i.e.…”

Neoadjuvant Chemotherapy without Radiation in Colorectal Cancer

“…The BACCHUS trial showed early exposure to a triplet NACT combination, FOLFOXIRI with bevacizumab did not impact adversely on compliance or surgical morbidity. 45 The Chinese randomized FOWARC study in rectal cancer show neoadjuvant FOLFOX without chemoradiotherapy achieves similar tumor downstaging rates of R0 resection, with lower rates of surgical morbidity than CRT. 43 Ongoing trials include a randomized phase II trial exploring the best sequence of CRT and NACT (NCT02008656) and the PROSPECT trial investigating NACT with FOLFOX and a selective use of CRT in early-stage patients with cT2N1 and cT3N0-1 rectal cancer.…”

“…In rectal cancer, a single published randomized phase III trial was identified, 43 and two randomized phase II studies, 44,45 nine prospective phase II, [46][47][48][49][50][51][52][53][54] and a single retrospective study 55 have been presented/published (►Table 2).…”

Predicting prognosis according to preoperative chemotherapy response in patients with locally advanced lower rectal cancer

“…NAC could compensate for such shortcomings, potentially yielding better survival outcomes. However, only few studies have reported the efficacy of NAC for LALRC without NACRT [7, 8].…”