EORTC 22921
Four arms phase III clinical trial for T3-T4 resectable rectal cancer comparing pre-operative pelvic irradiation to pre-operative irradiation combined with fluorouracil and leucovorin with or without post-operative adjuvant chemotherapy
Phase 3N = 1,011NCT00002523
- Population
- Patients with clinical stage T3 or T4 resectable rectal cancer
- Design
- Four-group randomised trial in patients with clinical stage T3 or T4 resectable rectal cancer. All received preoperative radiotherapy (45 Gy in 25 fractions over 5 weeks). Two courses of fluorouracil (350 mg/m2 per day) and leucovorin (20 mg/m2 per day) for 5 days were given with radiotherapy in two groups; four courses of adjuvant fluorouracil and leucovorin were planned in two groups (one of which had also received chemotherapy with radiotherapy). 1011 patients were randomised between April 1993 and March 2003 (252 to preoperative radiotherapy and 253 to each other group), using minimisation; the 2014 analysis was by intention to treat.
- Primary endpoint
- OS
- Arms
- Preoperative radiotherapy alone (control, n = 252): 45 Gy in 25 fractions over 5 weeks, then surgery; no chemotherapy before or after surgery
- Preoperative chemoradiotherapy (experimental, n = 253): 45 Gy in 25 fractions with two courses of fluorouracil and leucovorin, then surgery
- Preoperative radiotherapy then adjuvant chemotherapy (experimental, n = 253): 45 Gy in 25 fractions, surgery, then four courses of fluorouracil and leucovorin
- Preoperative chemoradiotherapy then adjuvant chemotherapy (experimental, n = 253): 45 Gy in 25 fractions with two courses of fluorouracil and leucovorin, surgery, then four courses of fluorouracil and leucovorin
- People
- Bosset JF
Δ 60-month Local recurrence−8.4 pointsΔ 120-month Local recurrence−10.6 pointsOSHR 0.99 (95% CI 0.83–1.18)OSHR 0.91 (95% CI 0.77–1.09)DFSHR 0.93 (95% CI 0.79–1.10)DFSHR 0.91 (95% CI 0.77–1.08)
Show the numbers
| Endpoint | Analysis | Preoperative chemoradiotherapy / Preoperative radiotherapy then adjuvant chemotherapy / Preoperative chemoradiotherapy then adjuvant chemotherapy | Preoperative radiotherapy alone | Effect |
|---|---|---|---|---|
| Local recurrenceRandomised patients (1011); analysis population not stated in the abstract5-year cumulative incidence of local recurrence | primaryBosset 2006 | 8.7% at 5 y | 17.1% at 5 y | P=0.002The primary end point was overall survival: no significant difference between groups that received chemotherapy preoperatively (P=0.84) or postoperatively (P=0.12); the combined 5-year overall survival rate for all four groups was 65.2%. Adherence to preoperative chemotherapy was 82.0% and to postoperative chemotherapy 42.9%. |
| Local recurrenceIntention-to-treat analysis (1011 randomised)10-year cumulative incidence of local relapse | long term-updatemedian follow-up 10.4 yearsBosset 2014 | 11.8% at 10 y (7.8–15.8%) | 22.4% at 10 y (17.1–27.6%) | P=0.0017The abstract reports no difference in the cumulative incidence of distant metastases (P=0.52) and no difference in the frequency of long-term side-effects between the four groups (P=0.22). |
| OSIntention-to-treat analysis (1011 randomised)10-year overall survival: preoperative radiotherapy versus preoperative radiotherapy with chemotherapy, as grouped in the abstract (primary end point) | long term-updatemedian follow-up 10.4 yearsBosset 2014 | — | — | HR 0.99 (95% CI 0.83–1.18)P=0.9110-year overall survival was 49.4% (95% CI 44.6-54.1) for the preoperative radiotherapy group and 50.7% (45.9-55.2) for the preoperative radiotherapy and chemotherapy group. |
| OSIntention-to-treat analysis (1011 randomised)10-year overall survival: adjuvant chemotherapy versus surveillance (primary end point) | long term-updatemedian follow-up 10.4 yearsBosset 2014 | — | — | HR 0.91 (95% CI 0.77–1.09)P=0.3210-year overall survival was 51.8% (95% CI 47.0-56.4) for the adjuvant chemotherapy group and 48.4% (43.6-53.0) for the surveillance group. |
| DFSIntention-to-treat analysis (1011 randomised)10-year disease-free survival: preoperative radiotherapy versus preoperative radiotherapy with chemotherapy, as grouped in the abstract | long term-updatemedian follow-up 10.4 yearsBosset 2014 | — | — | HR 0.93 (95% CI 0.79–1.10)P=0.3810-year disease-free survival was 44.2% (95% CI 39.5-48.8) for the preoperative radiotherapy group and 46.4% (41.7-50.9) for the preoperative radiotherapy and chemotherapy group. |
| DFSIntention-to-treat analysis (1011 randomised)10-year disease-free survival: adjuvant chemotherapy versus surveillance | long term-updatemedian follow-up 10.4 yearsBosset 2014 | — | — | HR 0.91 (95% CI 0.77–1.08)P=0.2910-year disease-free survival was 47.0% (95% CI 42.2-51.6) for the adjuvant chemotherapy group and 43.7% (39.1-48.2) for the surveillance group. |
| Endpoint | Analysis | Preoperative chemoradiotherapy / Preoperative radiotherapy then adjuvant chemotherapy / Preoperative chemoradiotherapy then adjuvant chemotherapy | Preoperative radiotherapy alone | Effect |
|---|---|---|---|---|
| Local recurrenceRandomised patients (1011); analysis population not stated in the abstract5-year cumulative incidence of local recurrence | primaryBosset 2006 | 8.7% at 5 y | 17.1% at 5 y | P=0.002The primary end point was overall survival: no significant difference between groups that received chemotherapy preoperatively (P=0.84) or postoperatively (P=0.12); the combined 5-year overall survival rate for all four groups was 65.2%. Adherence to preoperative chemotherapy was 82.0% and to postoperative chemotherapy 42.9%. |
| Local recurrenceIntention-to-treat analysis (1011 randomised)10-year cumulative incidence of local relapse | long term-updatemedian follow-up 10.4 yearsBosset 2014 | 11.8% at 10 y (7.8–15.8%) | 22.4% at 10 y (17.1–27.6%) | P=0.0017The abstract reports no difference in the cumulative incidence of distant metastases (P=0.52) and no difference in the frequency of long-term side-effects between the four groups (P=0.22). |
| OSIntention-to-treat analysis (1011 randomised)10-year overall survival: preoperative radiotherapy versus preoperative radiotherapy with chemotherapy, as grouped in the abstract (primary end point) | long term-updatemedian follow-up 10.4 yearsBosset 2014 | — | — | HR 0.99 (95% CI 0.83–1.18)P=0.9110-year overall survival was 49.4% (95% CI 44.6-54.1) for the preoperative radiotherapy group and 50.7% (45.9-55.2) for the preoperative radiotherapy and chemotherapy group. |
| OSIntention-to-treat analysis (1011 randomised)10-year overall survival: adjuvant chemotherapy versus surveillance (primary end point) | long term-updatemedian follow-up 10.4 yearsBosset 2014 | — | — | HR 0.91 (95% CI 0.77–1.09)P=0.3210-year overall survival was 51.8% (95% CI 47.0-56.4) for the adjuvant chemotherapy group and 48.4% (43.6-53.0) for the surveillance group. |
| DFSIntention-to-treat analysis (1011 randomised)10-year disease-free survival: preoperative radiotherapy versus preoperative radiotherapy with chemotherapy, as grouped in the abstract | long term-updatemedian follow-up 10.4 yearsBosset 2014 | — | — | HR 0.93 (95% CI 0.79–1.10)P=0.3810-year disease-free survival was 44.2% (95% CI 39.5-48.8) for the preoperative radiotherapy group and 46.4% (41.7-50.9) for the preoperative radiotherapy and chemotherapy group. |
| DFSIntention-to-treat analysis (1011 randomised)10-year disease-free survival: adjuvant chemotherapy versus surveillance | long term-updatemedian follow-up 10.4 yearsBosset 2014 | — | — | HR 0.91 (95% CI 0.77–1.08)P=0.2910-year disease-free survival was 47.0% (95% CI 42.2-51.6) for the adjuvant chemotherapy group and 43.7% (39.1-48.2) for the surveillance group. |
Data table
| Endpoint | HR | 95% CI |
|---|---|---|
| OS | 0.99 | 0.83–1.18 |
| OS | 0.91 | 0.77–1.09 |
| DFS | 0.93 | 0.79–1.1 |
| DFS | 0.91 | 0.77–1.08 |
Appears in
Sources
Bosset JF, Collette L, Calais G, Mineur L, Maingon P, Radosevic-Jelic L, et al. Chemotherapy with preoperative radiotherapy in rectal cancer. N Engl J Med. 2006;355(11):1114-23.
Bosset JF, Calais G, Mineur L, Maingon P, Stojanovic-Rundic S, Bensadoun RJ, et al. Fluorouracil-based adjuvant chemotherapy after preoperative chemoradiotherapy in rectal cancer: long-term results of the EORTC 22921 randomised study. Lancet Oncol. 2014;15(2):184-90.