CCTG CO.28 primary endpoint analysis: Neoadjuvant chemotherapy, excision and observation for early rectal cancer, the NEO trial.

Abstract

3508 Background: CO.28 (NCT03259035) is a phase II study designed to determine if patients with cT1-T3a/bN0 rectal cancer can be treated with induction chemotherapy (FOLFOX/CAPOX) and organ-preserving surgery. Methods: Patients with MRI staged cT1-3a/bN0 tumors and no pathologic (p) high risk features received 6/4 cycles of FOLFOX/CAPOX, repeat sigmoidoscopy/pelvic MRI and subsequent Transanal Endoscopic Surgery (TES) in the absence of tumor progression. ypT0/T1N0 tumors were treated with observation while ypT2+ or ypN+ stage were recommended Total Mesorectal Excision (TME). The primary endpoint was protocol specified Organ Preservation Rate (psOPR = ypT0/T1N0, no p high risk features) and actual Organ Preservation Rate (aOPR = ypT0/T1N0 stage plus higher yp stage patients who declined TME surgery). The study would be considered negative with an psOPR of 50% or lower (H0) and as promising if it is 65% or higher (H1). Results: Between 08/2017 to 05/2020, 58 eligible patients were accrued in Canada and the United States, median age was 67 years, 71% male. All had well-moderately differentiated, non-mucinous rectal adenocarcinoma and median tumor height was 6 cm (range 0-18). Median follow-up was 15.4 months. Chemotherapy with FOLFOX (32) or CAPOX (26) was administered, 90% completed all planned cycles. A total of 56/58 (97%) proceeded to TES, while one patient was ineligible due to tumor progression (1.7%) and one declined. In the intention to treat analysis, the psOPR was 57% (95% CI 43-70%) while the aOPR was 79% (95% CI 67% to 89%) due to 13/23 declining recommended TME surgery. Of 10 patients who proceeded to recommended TME, a complete R0 TME was performed in 9/10, and no p residual carcinoma was found in 7/10. Crude loco-regional (LR) and distant recurrence rates were 3.5% (95% CI 0.4 to 12%) and 0%, respectively. A recurrence occurred in 1/13 patients who initially declined TME surgery. Conclusions: In select patients with early stage rectal cancer, three months of induction CAPOX/FOLFOX followed by TES resulted in a high OPR without the use of pelvic irradiation. The observed high rate of pathologic downstaging may point to high chemo-responsiveness in early rectal adenocarcinoma with no p high risk features. Further trials to evaluate this approach are justified and updated results will be presented. Clinical trial information: NCT03259035. [Table: see text]