OPRA
A Phase II Multicenter Randomized Trial Evaluating 3-year Disease Free Survival in Patients With Locally Advanced Rectal Cancer Treated With Chemoradiation Plus Induction or Consolidation Chemotherapy and Total Mesorectal Excision or Non-operative Management
Phase 2N = 324NCT02008656
- Population
- Adults with stage II or III rectal adenocarcinoma
- Design
- Prospective randomised phase 2 trial in 324 patients with stage II or III rectal adenocarcinoma: induction chemotherapy then chemoradiotherapy (INCT-CRT; n=158) or chemoradiotherapy then consolidation chemotherapy (CRT-CNCT; n=166). All received 4 months of infusional fluorouracil-leucovorin-oxaliplatin or capecitabine-oxaliplatin and 5,000 to 5,600 cGy radiation with fluorouracil or capecitabine. Patients with a complete or near-complete response were offered watch-and-wait; total mesorectal excision was recommended for incomplete response. Designed as two stand-alone studies, each tested against a historical 3-year disease-free survival of 75%, not as a head-to-head comparison. Conducted at 18 US institutions (full text).
- Primary endpoint
- DFS
- Arms
- Induction chemotherapy then chemoradiotherapy (experimental, n = 158): Induction chemotherapy (infusional fluorouracil-leucovorin-oxaliplatin or capecitabine-oxaliplatin), then chemoradiotherapy (5,000 to 5,600 cGy with infusional fluorouracil or capecitabine); 4 months of chemotherapy in total
- Chemoradiotherapy then consolidation chemotherapy (experimental, n = 166): Chemoradiotherapy (5,000 to 5,600 cGy with infusional fluorouracil or capecitabine), then consolidation chemotherapy (infusional fluorouracil-leucovorin-oxaliplatin or capecitabine-oxaliplatin); 4 months of chemotherapy in total
- People
- Garcia-Aguilar J, senior author Saltz LB
Show the numbers
| Endpoint | Analysis | Induction chemotherapy then chemoradiotherapy / Chemoradiotherapy then consolidation chemotherapy | Control | Effect |
|---|---|---|---|---|
| DFSRandomised patients (324); the abstract does not label the analysis population3-year disease-free survival, tested for each group against a historical benchmark | primarymedian follow-up 3 yearsGarcia-Aguilar 2022 | 76% at 3 y (69–84%) | — | The abstract describes both rates as in line with the historical 3-year DFS rate of 75%. There was no head-to-head test of the two groups. |
| TME-free survivalRandomised patients (324); the abstract does not label the analysis population3-year TME-free survival (secondary endpoint) | primarymedian follow-up 3 yearsGarcia-Aguilar 2022 | 41% at 3 y (33–50%) | — | — |
| DFSRandomised patients (324: 158 and 166)5-year disease-free survival (updated analysis) | long term-updatemedian follow-up 5.1 yearsVerheij 2024 | 71% at 5 y (64–79%) | — | P=0.68 |
| TME-free survivalRandomised patients (324: 158 and 166)5-year TME-free survival (secondary endpoint, updated analysis) | long term-updatemedian follow-up 5.1 yearsVerheij 2024 | 39% at 5 y (32–48%) | — | P=0.012The abstract reports regrowth in 81 patients, of whom 94% had regrowth within 2 years and 99% within 3 years. Disease-free survival was 64% (95% CI 53 to 78) both for patients who had TME after restaging and for patients who had TME after regrowth (P=0.94). |
| Endpoint | Analysis | Induction chemotherapy then chemoradiotherapy / Chemoradiotherapy then consolidation chemotherapy | Control | Effect |
|---|---|---|---|---|
| DFSRandomised patients (324); the abstract does not label the analysis population3-year disease-free survival, tested for each group against a historical benchmark | primarymedian follow-up 3 yearsGarcia-Aguilar 2022 | 76% at 3 y (69–84%) | — | The abstract describes both rates as in line with the historical 3-year DFS rate of 75%. There was no head-to-head test of the two groups. |
| TME-free survivalRandomised patients (324); the abstract does not label the analysis population3-year TME-free survival (secondary endpoint) | primarymedian follow-up 3 yearsGarcia-Aguilar 2022 | 41% at 3 y (33–50%) | — | — |
| DFSRandomised patients (324: 158 and 166)5-year disease-free survival (updated analysis) | long term-updatemedian follow-up 5.1 yearsVerheij 2024 | 71% at 5 y (64–79%) | — | P=0.68 |
| TME-free survivalRandomised patients (324: 158 and 166)5-year TME-free survival (secondary endpoint, updated analysis) | long term-updatemedian follow-up 5.1 yearsVerheij 2024 | 39% at 5 y (32–48%) | — | P=0.012The abstract reports regrowth in 81 patients, of whom 94% had regrowth within 2 years and 99% within 3 years. Disease-free survival was 64% (95% CI 53 to 78) both for patients who had TME after restaging and for patients who had TME after regrowth (P=0.94). |
Appears in
Sources
Garcia-Aguilar J, Patil S, Gollub MJ, Kim JK, Yuval JB, Thompson HM, et al. Organ Preservation in Patients With Rectal Adenocarcinoma Treated With Total Neoadjuvant Therapy. J Clin Oncol. 2022;40(23):2546-2556.
Verheij FS, Omer DM, Williams H, Lin ST, Qin LX, Buckley JT, et al. Long-Term Results of Organ Preservation in Patients With Rectal Adenocarcinoma Treated With Total Neoadjuvant Therapy: The Randomized Phase II OPRA Trial. J Clin Oncol. 2024;42(5):500-506.