ADORE: trial | Bending the Curve: Trial by Trial

ADORE

Randomized phase II study of adjuvant chemotherapy with 5-FU/leucovorin vs oxaliplatin/5-FU/leucovorin after preoperative chemoradiotherapy with fluoropyrimidines followed by surgery in patients with locally advanced rectal cancer

Phase 2N = 321NCT00807911

Population

Patients with postoperative pathological stage II (ypT3-4N0) or III (ypTanyN1-2) rectal cancer after preoperative fluoropyrimidine-based chemoradiotherapy and total mesorectal excision

Design

Open-label, multicentre, phase 2 randomised trial in patients with postoperative pathological stage II (ypT3-4N0) or III (ypTanyN1-2) rectal cancer after preoperative fluoropyrimidine-based chemoradiotherapy and total mesorectal excision. Randomised 1:1 to four cycles of fluorouracil and leucovorin (fluorouracil 380 mg/m2 and leucovorin 20 mg/m2 on days 1-5, every 4 weeks) or eight cycles of FOLFOX (oxaliplatin 85 mg/m2, leucovorin 200 mg/m2, fluorouracil bolus 400 mg/m2 on day 1 and fluorouracil infusion 2400 mg/m2 for 46 h, every 2 weeks). 321 patients were randomised between November 2008 and June 2012 (161 and 160). Primary endpoint: 3-year disease-free survival, analysed by intention to treat. There was no observation arm.

Primary endpoint

DFS

Arms

Adjuvant fluorouracil and leucovorin (control, n = 161): Four cycles of fluorouracil 380 mg/m2 and leucovorin 20 mg/m2 on days 1-5, every 4 weeks
Adjuvant FOLFOX (experimental, n = 160): Eight cycles of oxaliplatin 85 mg/m2, leucovorin 200 mg/m2, fluorouracil bolus 400 mg/m2 on day 1 and fluorouracil infusion 2400 mg/m2 over 46 hours, every 2 weeks

People

Hong YS

DFSHR 0.657 (95% CI 0.434–0.994)Δ 36-month DFS+8.7 pointsDFSHR 0.63 (95% CI 0.43–0.93)Δ 72-month DFS+11.4 pointsOSHR 0.73 (95% CI 0.45–1.19)Δ 72-month OS+1.7 points

Show the numbers

Results reported for ADORE
Endpoint	Analysis	Adjuvant FOLFOX	Adjuvant fluorouracil and leucovorin	Effect
DFSIntention-to-treat analysis (321 randomised)3-year disease-free survival (primary endpoint)	primarymedian follow-up 38.2 monthsHong 2014	71.6% at 3 y (64.6–78.6%)	62.9% at 3 y (55.4–70.4%)	HR 0.657 (95% CI 0.434–0.994)P=0.047Median follow-up 38.2 months (IQR 26.4-50.6). This is a comparison of two chemotherapy regimens; there was no observation arm.
DFSIntention-to-treat analysis (321 randomised)6-year disease-free survival; stratified hazard ratio	long term-updateHong 2019	68.2% at 6 y	56.8% at 6 y	HR 0.63 (95% CI 0.43–0.93)P=0.018
OSRandomised patients (321); analysis population not stated in the abstract6-year overall survival	long term-updateHong 2019	78.1% at 6 y	76.4% at 6 y	HR 0.73 (95% CI 0.45–1.19)P=0.21

Results reported for ADORE
Endpoint	Analysis	Adjuvant FOLFOX	Adjuvant fluorouracil and leucovorin	Effect
DFSIntention-to-treat analysis (321 randomised)3-year disease-free survival (primary endpoint)	primarymedian follow-up 38.2 monthsHong 2014	71.6% at 3 y (64.6–78.6%)	62.9% at 3 y (55.4–70.4%)	HR 0.657 (95% CI 0.434–0.994)P=0.047Median follow-up 38.2 months (IQR 26.4-50.6). This is a comparison of two chemotherapy regimens; there was no observation arm.
DFSIntention-to-treat analysis (321 randomised)6-year disease-free survival; stratified hazard ratio	long term-updateHong 2019	68.2% at 6 y	56.8% at 6 y	HR 0.63 (95% CI 0.43–0.93)P=0.018
OSRandomised patients (321); analysis population not stated in the abstract6-year overall survival	long term-updateHong 2019	78.1% at 6 y	76.4% at 6 y	HR 0.73 (95% CI 0.45–1.19)P=0.21

Hazard ratio (95% CI) by endpoint. Values below 1 favour the experimental arm.

Data table

Endpoint	HR	95% CI
DFS	0.657	0.434–0.994
DFS	0.63	0.43–0.93
OS	0.73	0.45–1.19

Appears in

2014 Adjuvant chemotherapy after preoperative (chemo)radiotherapy

Sources

Hong YS, Nam BH, Kim KP, Kim JE, Park SJ, Park YS, et al. Oxaliplatin, fluorouracil, and leucovorin versus fluorouracil and leucovorin as adjuvant chemotherapy for locally advanced rectal cancer after preoperative chemoradiotherapy (ADORE): an open-label, multicentre, phase 2, randomised controlled trial. Lancet Oncol. 2014;15(11):1245-53.
PubMed DOI
Hong YS, Kim SY, Lee JS, Nam BH, Kim KP, Kim JE, et al. Oxaliplatin-Based Adjuvant Chemotherapy for Rectal Cancer After Preoperative Chemoradiotherapy (ADORE): Long-Term Results of a Randomized Controlled Trial. J Clin Oncol. 2019;37(33):3111-3123.
PubMed DOI