PREOPANC
Preoperative chemoradiotherapy versus immediate surgery for resectable and borderline resectable pancreatic cancer (Dutch randomised phase III PREOPANC trial)
Phase 3N = 246
- Population
- Patients with resectable or borderline resectable pancreatic cancer; 246 eligible patients randomised.
- Design
- Randomised phase 3 trial in 16 Dutch centres (1:1). Neoadjuvant arm: three courses of gemcitabine, with radiotherapy (15 fractions of 2.4 Gy, 36 Gy in total per the 2022 report) during the second course, then surgery and four courses of adjuvant gemcitabine. Control: immediate surgery and six courses of adjuvant gemcitabine. Primary endpoint overall survival by intention to treat. Recruitment April 2013 to July 2017. The 2022 paper is a long-term analysis of the same randomisation. Registered in the Netherlands Trial Register (NTR3709) and the EU Clinical Trials Register (EudraCT 2012-003181-40) per the trial's protocol publication (Trials 2016, PMC4784417); no ClinicalTrials.gov record was found.
- Primary endpoint
- OS
- Arms
- Upfront surgery (control, n = 127): Immediate surgery followed by six courses of adjuvant gemcitabine
- Neoadjuvant chemoradiotherapy (experimental, n = 119): Three courses of gemcitabine with radiotherapy during the second course, then surgery and four courses of adjuvant gemcitabine
- People
- Versteijne E
OSHR 0.78 (95% CI 0.58–1.05)Δ median OS+1.7 monthsΔ Resection rate−11 pointsΔ R0 resection+31 pointsOSHR 0.73 (95% CI 0.56–0.96)Δ median OS+1.4 months
Show the numbers
| Endpoint | Analysis | Neoadjuvant chemoradiotherapy | Upfront surgery | Effect |
|---|---|---|---|---|
| OS | primaryVersteijne 2020 | median 16 months | median 14.3 months | HR 0.78 (95% CI 0.58–1.05)P=.096The authors report no significant overall survival benefit in this primary analysis. |
| Resection rateRandomised eligible patients (119 and 127); the abstract does not label the population, and the denominators follow from the R0 counts (72 of 119, 92 of 127) | primaryVersteijne 2020 | 61% | 72% | P=.058Resection rate, a secondary outcome. |
| R0 resectionResected patients (72 neoadjuvant, 92 upfront surgery); the abstract does not define the denominators | primaryVersteijne 2020 | 71% | 40% | P<.00151 of 72 versus 37 of 92 patients. The denominators are not the randomised totals; they are consistent with the numbers resected (61% of 119 and 72% of 127). |
| OSRandomised eligible patients (246); analysis population not labelled in the abstract (the primary outcome is stated as OS by intention to treat) | long term-updatemedian follow-up 59 monthsVersteijne 2022 | median 15.7 months; 20.5% at 5 y (14.2–29.8%) | median 14.3 months; 6.5% at 5 y (3.1–13.7%) | HR 0.73 (95% CI 0.56–0.96)P=.025Long-term follow-up of the same randomisation as the 2020 report, not a separate trial. The abstract notes that the median difference was only 1.4 months while the 5-year rates differed more. |
| Endpoint | Analysis | Neoadjuvant chemoradiotherapy | Upfront surgery | Effect |
|---|---|---|---|---|
| OS | primaryVersteijne 2020 | median 16 months | median 14.3 months | HR 0.78 (95% CI 0.58–1.05)P=.096The authors report no significant overall survival benefit in this primary analysis. |
| Resection rateRandomised eligible patients (119 and 127); the abstract does not label the population, and the denominators follow from the R0 counts (72 of 119, 92 of 127) | primaryVersteijne 2020 | 61% | 72% | P=.058Resection rate, a secondary outcome. |
| R0 resectionResected patients (72 neoadjuvant, 92 upfront surgery); the abstract does not define the denominators | primaryVersteijne 2020 | 71% | 40% | P<.00151 of 72 versus 37 of 92 patients. The denominators are not the randomised totals; they are consistent with the numbers resected (61% of 119 and 72% of 127). |
| OSRandomised eligible patients (246); analysis population not labelled in the abstract (the primary outcome is stated as OS by intention to treat) | long term-updatemedian follow-up 59 monthsVersteijne 2022 | median 15.7 months; 20.5% at 5 y (14.2–29.8%) | median 14.3 months; 6.5% at 5 y (3.1–13.7%) | HR 0.73 (95% CI 0.56–0.96)P=.025Long-term follow-up of the same randomisation as the 2020 report, not a separate trial. The abstract notes that the median difference was only 1.4 months while the 5-year rates differed more. |
Data table
| Endpoint | HR | 95% CI |
|---|---|---|
| OS | 0.78 | 0.58–1.05 |
| OS | 0.73 | 0.56–0.96 |
- Neoadjuvant chemoradiotherapy (experimental)
- Upfront surgery (control)
Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.
Data table (modelled values)
| Months | Neoadjuvant chemoradiotherapy | Upfront surgery |
|---|---|---|
| 0 | 100.0% | 100.0% |
| 10 | 64.8% | 61.6% |
| 20 | 42.0% | 37.9% |
| 30 | 27.3% | 23.4% |
| 40 | 17.7% | 14.4% |
- Neoadjuvant chemoradiotherapy (experimental)
- Upfront surgery (control)
Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.
Data table (modelled values)
| Months | Neoadjuvant chemoradiotherapy | Upfront surgery |
|---|---|---|
| 0 | 100.0% | 100.0% |
| 10 | 64.3% | 61.6% |
| 20 | 41.4% | 37.9% |
| 29 | 27.8% | 24.5% |
| 39 | 17.9% | 15.1% |
Appears in
Sources
Versteijne E, Suker M, Groothuis K, Akkermans-Vogelaar JM, Besselink MG, Bonsing BA, et al. Preoperative Chemoradiotherapy Versus Immediate Surgery for Resectable and Borderline Resectable Pancreatic Cancer: Results of the Dutch Randomized Phase III PREOPANC Trial. J Clin Oncol. 2020;38(16):1763-1773.
Versteijne E, van Dam JL, Suker M, Janssen QP, Groothuis K, Akkermans-Vogelaar JM, et al. Neoadjuvant Chemoradiotherapy Versus Upfront Surgery for Resectable and Borderline Resectable Pancreatic Cancer: Long-Term Results of the Dutch Randomized PREOPANC Trial. J Clin Oncol. 2022;40(11):1220-1230.