Type of publication:
Conference abstract
Author(s):
Sebag-Montefiore D.; Samuel L.; *Gollins S.; Glynne-Jones R.; Harte R.; West N.; Quirke P.; Myint A.S.; Bach S.; Falk S.; Parsons P.; Dhadda A.; Misra V.; Brown G.; Harrison M.; White L.; Duggan M.; Begum R.; Chang E.; Musleh R.; Lopes A.; Adams R.
Citation:
Radiotherapy and Oncology. Conference: ESTRO 2025. Vienna Austria. 206(Supplement 1) (pp S1192-S1194), 2025. Date of Publication: 01 May 2025
Abstract:
Purpose/Objective: To determine if the addition of irinotecan to capecitabine chemoradiation (CRT) improves disease-free survival in MRI-defined locally advanced rectal cancer (LARC). Material/Methods: ARISTOTLE (ISRCTN:09351447) is a phase III, multi-centre, open-label trial that randomly assigned (1:1) patients with MRI-defined LARC threatening or involving resection margins without metastases to pre-operative radiotherapy:45Gy/25 fractions combined with either capecitabine 900mg/m2 (CRT) or 650 mg/m2 bd weekdays with Irinotecan iv once-weekly 60mg/m2 (IrCRT) weeks 1-4. The primary endpoint is disease-free survival (DFS). Result(s): 75 UK sites randomised 564 eligible patients from 10/2011 to 07/2018; 284 to CRT and 280 to IrCRT. 66% male; median age 61 years (range:24-83). Radiological staging in both arms was similar:mrT3(77%), mrT4(16%); mrCRM involved(49%);resection margin threatened <=1mm(38%). Median follow-up is 62.1 months.Compared with CRT, IrCRT patients were less likely to receive 45Gy RT: 208(75%) vs 251(89%), p < 0.001; or receive >=90% capecitabine dose:187(68%) in IrCRT vs 253(89%) CRT, p < 0.001. 205(74%) IrCRT patients received >=90% irinotecan dose. >=Gd 3 non-haematological adverse events included fatigue 17(6%) vs 8(3%) p=0.06; diarrhoea:14% vs 4% p<0.001; abdominal pain 5% vs <1% p=0.001 for IrCRT and CRT respectively. >=Gd 3 haematological adverse events included leucopaenia: 9% vs 2%, p<0.001; neutropaenia: 10% vs 1%,p<0.001; and febrile neutropaenia: 1% vs <1% for IrCRT and CRT respectively. 5 patients had a grade 5 adverse event (3 lrCRT,2 CRT). The median time from the end of RT to surgery was 10.6 weeks. 238(85%) and 243(86%) patients underwent surgery in the IrCRT and CRT arms. The R0 resection rate was 90% vs 89% p=0.75 for IrCRT and CRT respectively. The pCR rate was 20% for IrCRT vs 18% for CRT p = 0.52. The rate of any post-surgical complications was similar in both arms:94(39%) for IrCRT and 91(37%) for CRT p=0.65). There is no evidence of a difference in loco-regional failure free (HR 0.94 [0.46-1.90]p=0.86, distant metastasis free (HR 0.89 [0.63-1.25] p=0.51), disease free HR 0.87 [0.64-1.18] p=0.37) or overall survival (HR 0.91[0.63-1.30],p=0.59) when IrCRT is compared with CRT. Conclusion(s): For patients with MRI-defined high risk LARC, low rates of CRM involvement and 36 month loco-regional failure were observed.The addition of irinotecan to CRT was associated with decreased radiotherapy and chemotherapy compliance and a higher rate of adverse events.There is no evidence of a difference in the pCR rate,36 month locoregional recurrence free or disease-free survival.
DOI: 10.1016/S0167-8140%2825%2900901-6
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