602P - Brazil-TNT: A randomized phase II trial of neo-adjuvant chemoradiation followed by FOLFIRINOX vs chemoradiation for stage II/III rectal cancer

Background

Neoadjuvant radiation and oxaliplatin-based systemic therapy (Total Neoadjuvant Therapy – TNT) has been shown to increase response and organ-preservation rates in localized rectal cancer. However, trials have been heterogeneous regarding treatment protocols and few have used a watch-and-wait (WW) approach for complete responders. This trial evaluates if conventional long-term chemoradiation followed by consolidation FOLFIRINOX increases complete response rates and number of patients managed by WW.

Methods

Thiswas apragmatic randomized phase II trial conducted in 2 Cancer Centers in Brazil that included patients with T3+ or N+ rectal adenocarcioma. After completing long-course 54Gy chemoradiation with capecitabine patients were randomized 1:1 to observation or 4 cycles of mFOLFIRINOX (Oxaliplatin 85, irinotecan 135, 5-FU 2400). All patients were re-staged with dedicated pelvic MRI and sigmoidoscopy 12 weeks after the end of radiation. Patients with a clinical complete response were followed using a WW protocol. Primary enpoint was complete response: complete clinical response (cCR) or pathological response(pCR).

Results

Between Feb 2020 and April 2023, 46 patients were randomized to TNT and 42 to standard of care. Median age was 59 and 64% were male. Tumors were 68% stage 3, median distance from anal verge was 5cm, 43% had at-risk circumferential margin and 21% involved sphincter. The rates of cCR+pCR were 9/46 (19%) for TNT vs 5/42 (11%) for controls (OR 1.79, CI95% 0.54-6.3 p=0.16) and rates of WW were 5/46 (10.8%) and 2/45 (4%) (ns). Median follow-up was 16.9 months and recurrence rates were 8/46 (17%) and 11/42 (26%) for TNT and controls (ns).

Conclusions

TNT with consolidation FOLFIRINOX is feasible and has high response rates. Complete data from 96 patients will be presented at the meeting. This trial was supported by a grant from the Brazilian Ministry of Health (PROADI-SUS) - NUP 25000.164382/2020-81.

Clinical trial identification

NCT05081687.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Brazilian Ministry of Health - "PROADI-SUS".

Disclosure

All authors have declared no conflicts of interest.