ARISTOTLE: A phase III trial comparing concurrent capecitabine with capecitabine and irinotecan (Ir) chemoradiation as preoperative treatment for MRI-defined locally advanced rectal cancer (LARC).

• DOI: 10.1200/jco.2020.38.15_suppl.4101
• Publication Date: 2020-05-25T15:25:21Z
• Authors: David Sebag-Monte...; Richard Adams; Simon Gollins; Leslie M. Samuel; Robert Glynne-Jones; Robert Harte; Nicholas West; Philip Quirke; Arthur Sun Myint; Simon P Bach; Philip Parsons; Stephen Falk; Amandeep Singh Dh...; Vivek Misra; Nick Brown; Gina Brown; Mark Harrison; Laura White; Marian Duggan; Andre Lopes
• Keywords: Clinical endpoint; Chemoradiotherapy

4101 Background: Phase II studies reported high pathological complete response (pCR) rates and acceptable toxicity using irinotecan fluoropyrimidine chemoradiation in LARC (ISRCTN:09351447). Methods: This phase III, multicentre, open-label trial funded by Cancer Research UK, randomly assigned (1:1) patients with MRI defined threatening or involving resection margins without metastases, to pre-operative radiotherapy (RT) 45Gy/25 fractions combined either capecitabine 900mg/m 2 (CRT) 650 mg/m2 bd weekdays Irinotecan iv once-weekly 60mg/m2 weeks 1-4 (IrCRT). The primary endpoint is disease-free survival (DFS). Secondary endpoints include treatment compliance, safety pCR. Results: 75 UK sites randomised 564 eligible from Oct/11 July/18; 284 CRT 280 IrCRT. 370 (66%) male; median age 61 years (range:29-83). Staging both arms was similar: mrT3 (432/564(77%), mrT4 (89/564(16%); mrCRM involved (275/564(49%); threatened ≤1mm (215/564(38%). Compared CRT, IrCRT were less likely receive 45Gy RT (207/276(75%) vs 251/283(89%), p < 0.001) ≥90% dose 188/276(68%) 253/283(89.4%)p 0.001). A total of 204/276(74%) received dose. grade 3-4 gastrointestinal adverse event rate 21%(58/276) 12%(34/283) (p = 0.004). Patients receiving had significantly more diarrhoea 38/276(13.8%) 10/283(3.5%)p neutropenia 27/276(9.8%) 3/283 (1.1%) Two three experienced a related death. 237/276(86%) 241/283(85%) surgery. time end surgery(10.6 weeks), the surgical procedure APE 262/478(55%), AR 189/478(40%), Hartmann’s 10/478(2%); complications(any event) 38%(181/478) similar arms. pCR available > 95% 20.2%(46/228) for IrCRTvs.17.4%(40/230) 0.45), 84% CRM-ve Conclusions: For risk low CRM involvement observed reflecting quality multidisciplinary care. addition did not improve rate, associated decrease compliance higher events. Surgical complications unaffected. Longer follow-up required assess DFS translational data. Clinical information: 09351447 .