PROSPECT
A Phase II/III Trial of Neoadjuvant FOLFOX With Selective Use of Combined Modality Chemoradiation Versus Preoperative Combined Modality Chemoradiation for Locally Advanced Rectal Cancer Patients Undergoing Low Anterior Resection With Total Mesorectal Excision (PROSPECT)
Phase 2/3N = 1,194NCT01515787
- Population
- Adults with rectal cancer clinically staged as T2 node-positive, T3 node-negative or T3 node-positive who were candidates for sphincter-sparing surgery
- Design
- Multicentre, unblinded, noninferiority randomised trial: neoadjuvant FOLFOX (with chemoradiotherapy only if the primary tumour decreased in size by less than 20% or FOLFOX was stopped because of side effects) versus chemoradiotherapy before surgery. 1194 patients were randomised from June 2012 to December 2018 and 1128 started treatment (585 FOLFOX, 543 chemoradiotherapy). Noninferiority would be claimed if the upper limit of the two-sided 90.2% confidence interval of the hazard ratio for disease recurrence or death did not exceed 1.29.
- Primary endpoint
- DFS
- Arms
- Chemoradiotherapy (control, n = 543): Preoperative fluorouracil-based chemoradiotherapy, then surgery
- FOLFOX with selective chemoradiotherapy (experimental, n = 585): Neoadjuvant FOLFOX, with chemoradiotherapy only if the tumour decreased in size by less than 20% or FOLFOX was discontinued because of side effects, then surgery
- People
- Schrag D, senior author Mamon HJ
DFSHR 0.92Δ 60-month DFS+2.2 pointsOSHR 1.04 (95% CI 0.74–1.44)Local recurrenceHR 1.18 (95% CI 0.44–3.16)
Show the numbers
| Endpoint | Analysis | FOLFOX with selective chemoradiotherapy | Chemoradiotherapy | Effect |
|---|---|---|---|---|
| DFSPer-protocol population as stated in the full text (all patients who received any dose of treatment: 585 FOLFOX, 543 chemoradiotherapy); not labelled in the abstractDisease-free survival, noninferiority comparison (primary endpoint); hazard ratio for disease recurrence or death | primarymedian follow-up 58 monthsSchrag 2023 | 80.8% at 5 y (77.9–83.7%) | 78.6% at 5 y (75.4–81.8%) | HR 0.92P=0.005The hazard ratio's interval is a 90.2% CI of 0.74 to 1.14 (noninferiority margin 1.29), so it is not entered as a 95% interval. P value is for noninferiority. Five-year disease-free survival is given with 95% CIs. Full text: a supplementary analysis of all 1194 randomised patients gave a hazard ratio of 0.91 (90.2% CI 0.73 to 1.13). |
| OSAnalysis population not stated in the abstractOverall survival (secondary endpoint); hazard ratio for death | primarymedian follow-up 58 monthsSchrag 2023 | — | — | HR 1.04 (95% CI 0.74–1.44)The abstract describes overall survival as similar between groups; no survival rates are given. |
| Local recurrenceAnalysis population not stated in the abstractLocal recurrence in a time-to-event analysis (secondary endpoint); hazard ratio | primarymedian follow-up 58 monthsSchrag 2023 | — | — | HR 1.18 (95% CI 0.44–3.16)The abstract describes local recurrence as similar between groups; no recurrence rates are given. |
| Endpoint | Analysis | FOLFOX with selective chemoradiotherapy | Chemoradiotherapy | Effect |
|---|---|---|---|---|
| DFSPer-protocol population as stated in the full text (all patients who received any dose of treatment: 585 FOLFOX, 543 chemoradiotherapy); not labelled in the abstractDisease-free survival, noninferiority comparison (primary endpoint); hazard ratio for disease recurrence or death | primarymedian follow-up 58 monthsSchrag 2023 | 80.8% at 5 y (77.9–83.7%) | 78.6% at 5 y (75.4–81.8%) | HR 0.92P=0.005The hazard ratio's interval is a 90.2% CI of 0.74 to 1.14 (noninferiority margin 1.29), so it is not entered as a 95% interval. P value is for noninferiority. Five-year disease-free survival is given with 95% CIs. Full text: a supplementary analysis of all 1194 randomised patients gave a hazard ratio of 0.91 (90.2% CI 0.73 to 1.13). |
| OSAnalysis population not stated in the abstractOverall survival (secondary endpoint); hazard ratio for death | primarymedian follow-up 58 monthsSchrag 2023 | — | — | HR 1.04 (95% CI 0.74–1.44)The abstract describes overall survival as similar between groups; no survival rates are given. |
| Local recurrenceAnalysis population not stated in the abstractLocal recurrence in a time-to-event analysis (secondary endpoint); hazard ratio | primarymedian follow-up 58 monthsSchrag 2023 | — | — | HR 1.18 (95% CI 0.44–3.16)The abstract describes local recurrence as similar between groups; no recurrence rates are given. |
Data table
| Endpoint | HR | 95% CI |
|---|---|---|
| OS | 1.04 | 0.74–1.44 |
| Local recurrence | 1.18 | 0.44–3.16 |