Table 1.
Clinical trials that investigate total neoadjuvant therapy in rectal cancer.
| Trial | N | Preoperative treatment | Postoperative treatment | Results |
|---|---|---|---|---|
| RAPIDO40,41,44 | 920 | Arm A: SCPRT + 9 cycles FOLFOX4 or 6 cycles
CAPOX Arm B: 5-FU-based CRT |
Optional (12 cycles FOLFOX4 or 8 cycles CAPOX) | ● pCR: 28% versus 14%
(p < 0.001) ● 3-year DrTF (primary endpoint): 23.7% versus 30.4% (p = 0.019) |
| Polish-II47,48 | 515 | Arm A: 5× 5 Gy + 3 cycles of FOLFOX4 Arm B: 5-FU-based CRT |
At discretion of treating physicians | ● pCR: 16% versus 12%
(n.s.) ● R0-resection (primary endpoint): 77% versus 71% (p = 0.07, n.s.) ● 3-year DFS: 53% versus 52% (p = 0.85, n.s.) ● 7-year OS: n.s. |
| PRODIGE 23 39 | 461 | Arm A: 6 cycles FOLFIRINOX + CRT Arm B: 5-FU-based CRT |
FOLFOX or capecitabine | ● pCR: 27.5% versus 11.7%
(p < 0.001) ● 3-year DFS (primary endpoint): 75.7% versus 68.5% (p = 0.034) |
| CAO/ARO/AIO-12 45 | 306 | Arm A (induction CT): 3 cycles FOLFOX + CRT Arm B (consolidation CT): CRT + 3 cycles FOLFOX |
No | ● pCR (primary endpoint): Arm A, 17% (n.s.); Arm B, 25%
(p < 0.001) Survival data pending |
| OPRA 46 | 306 | I-Arm (induction): 8 cycles FOLFOX or 5 cycles
CAPOX + CRT C-Arm (consolidation): CRT + 8 cycles FOLFOX or 5 cycles CAPOX |
No | ● 3-year DFS (primary endpoint): 78% in I-Arm versus 77% in C-Arm (n.s.) |
| NCT0033581642,43 | 292 | Arm 1: 5-FU-based CRT Arm 2: CRT + 2 cycles FOLFOX6 Arm 3: CRT + 4 cycles FOLFOX6 Arm 4: CRT + 6 cycles FOLFOX6 |
Optional, investigator’s choice | ● pCR (primary endpoint): 18%, 25%, 30%, and 38% in Arms
1, 2, 3, and 4
(p = 0.0036) ● 5-year DFS: 50%, 81%, 86%, and 76% in Arms 1, 2, 3, and 4 (p = 0.004) ● 5-year OS: 79%, 92%, 88%, and 84% in Arms 1, 2, 3, and 4 (n.s.) |
| STELLAR 49 | 599 | Arm 1: SCPRT + 4× CAPOX Arm 2: CRT |
CAPOX | ● pCR + cCR rate (primary endpoint): 22.5%
versus 12.6%
(p = 0.001) 3-year DFS: 64.5% versus 62.3% (noninferiority: p < 0.001) 3-year OS: 86.5% versus 75.1% (p = 0.036) |
CAPOX, capecitabine/oxaliplatin; cCR, clinical complete response; CRT, chemoradiotherapy; CT, chemotherapy; DFS, disease-free survival; DrTF, disease-related treatment failure; FOLFIRINOX, leucovorin/fluorouracil/irinotecan/oxaliplatin; FOLFOX, leucovorin/fluorouracil/oxaliplatin; N, number of evaluable patients; n.s., not significant; OS, overall survival; pCR, pathological complete response; SCPRT, short-course preoperative radiotherapy.