571P - Neoadjuvant chemotherapy with FOLFIRINOX and short course radiotherapy in locally advanced rectal caner (ISANOX): A prospective phase II trial

Background

Total neoadjuvant treatment (TNT) combining induction or consolidation chemotherapy with chemoradiotherapy (RCT) or short course RT is a novel approach in the management of locally advanced rectal cancer (LARC). TNT improved local control with significantly higher pathologic complete response (pCR) compared to RCT. ISANOX trial aimed to improve pathologic pCR compared to RCT.

Methods

We did a single arm phase 2 prospective trial. Patients were eligible if they were aged 18 years or older, with a performance status of 0–1,newly diagnosed, biopsy proven LARC, classified on pelvic MRI : clinical tumour [cT] stage cT3 or cT4 and/or, positive clinical nodal [cN] stage. Participants were assigned to receive six cycles of modified FOLFIRINOX followed by short course RT then 2 cycles of modified FOLFOX. Surgery was performed 6 to 8 weeks after completion of RT. After surgery they received four cycles of mFOLFOX6 irrespective of pathologic response. The primary end point was pCR rate. Safety and tolerability were assessed. This trial is registered ClinicalTrials.gov NCT05868317.

Results

One hundred fourteen patients were enrolled and 100 achieved the treatment. Median age was 57 years. The study included 49 women and 51 men, with 62 % middle and 38 % low rectal tumors. Disease was cT2, cT3, cT4 in 10%, 81% and 9% respectively. 93 % were cN positive. All patients received IC with modified FOLFIRINOX. Grade 3/4 adverse events occurred in 8 of 100 patients (8%). 99 patients completed RT and Consolidation with modified Folfox. After neoadjuvant treatment, 4 patients achieved a complete clinical response and were offered watch and wait strategy, one patient progressed, 1 refused surgery. 93 patients were operated, 2 had a local excision, 73 (78%) an anterior resection and 18 (19%) and abdominoperineal resection. 23 (25%) patients achieved à pCR on histological examination. Treatment-related deaths occurred in one patient in the neoadjuvant chemotherapy.

Conclusions

Induction chemotherapy with mFOLFIRINOX followed by short course RT and mFOLFOX in LARC was associated to important pCR rate with good tolerance. Therefore, ISANOX could be an option in the neoadjuvant setting but these data must be validated in further studies.

Clinical trial identification

NCT05868317.

Editorial acknowledgement

Legal entity responsible for the study

Feryel Letaief Ksontini.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.