PRIME
A Randomized, Multicenter, Phase 3 Study to Compare the Efficacy of Panitumumab in Combination With Oxaliplatin/ 5-fluorouracil/ Leucovorin to the Efficacy of Oxaliplatin/ 5-fluorouracil/ Leucovorin Alone in Patients With Previously Untreated Metastatic Colorectal Cancer
Phase 3N = 1,183NCT00364013
- Population
- Previously untreated metastatic colorectal cancer
- Design
- Multicentre randomised phase 3 trial (1:1) of panitumumab plus FOLFOX4 versus FOLFOX4 alone as first-line treatment of metastatic colorectal cancer (ECOG performance status 0 to 2, tissue available for biomarker testing). The primary endpoint was progression-free survival and overall survival was secondary. Results were prospectively analysed by tumour KRAS status; KRAS results were available for 93% of the 1,183 patients randomly assigned. The 2013 report is a prospective-retrospective analysis by RAS (KRAS or NRAS) and BRAF status.
- Primary endpoint
- PFS
- Arms
- FOLFOX4 (control): FOLFOX4 (infusional fluorouracil, leucovorin, oxaliplatin)
- Panitumumab plus FOLFOX4 (experimental): Panitumumab plus FOLFOX4
- People
- Douillard JY
PFSHR 0.80 (95% CI 0.66–0.97)Δ median PFS+1.6 monthsOSHR 0.83 (95% CI 0.67–1.02)Δ median OS+4.2 monthsPFSHR 1.29 (95% CI 1.04–1.62)OSHR 1.24 (95% CI 0.98–1.57)
Show the numbers
| Endpoint | Analysis | Panitumumab plus FOLFOX4 | FOLFOX4 | Effect |
|---|---|---|---|---|
| PFSWild-type KRAS stratum (analysed on an intention-to-treat basis by tumour KRAS status, as stated in the abstract) | primaryDouillard 2010 | median 9.6 months | median 8 months | HR 0.80 (95% CI 0.66–0.97)P=0.02Hazard ratio for progression or death, panitumumab-FOLFOX4 versus FOLFOX4, in the wild-type KRAS stratum. The 2013 report describes the patients in this analysis as those without KRAS mutations in exon 2. |
| OSWild-type KRAS stratum (analysed on an intention-to-treat basis by tumour KRAS status, as stated in the abstract) | primaryDouillard 2010 | median 23.9 months | median 19.7 months | HR 0.83 (95% CI 0.67–1.02)P=0.072Secondary endpoint; the abstract calls the increase in overall survival nonsignificant. |
| PFSMutant KRAS stratum (analysed on an intention-to-treat basis by tumour KRAS status, as stated in the abstract) | exploratoryDouillard 2010 | — | — | HR 1.29 (95% CI 1.04–1.62)P=0.02Hazard ratio above 1 means shorter progression-free survival with panitumumab-FOLFOX4 than with FOLFOX4 in the mutant KRAS stratum. |
| OSMutant KRAS stratum (analysed on an intention-to-treat basis by tumour KRAS status, as stated in the abstract) | exploratoryDouillard 2010 | median 15.5 months | median 19.3 months | HR 1.24 (95% CI 0.98–1.57)P=0.068Secondary endpoint; the abstract gives the medians as 'respectively' after naming the panitumumab-FOLFOX4 and FOLFOX4 arms in that order. |
| PFSRAS wild-type (no KRAS or NRAS mutation; 512 patients without RAS mutations), prospective-retrospective analysis | exploratoryDouillard 2013 | median 10.1 months | median 7.9 months | HR 0.72 (95% CI 0.58–0.90)P=0.004Prospective-retrospective analysis of PRIME by RAS (KRAS or NRAS) status; 512 patients without RAS mutations. Hazard ratio for progression or death with panitumumab-FOLFOX4. |
| OSRAS wild-type (no KRAS or NRAS mutation; 512 patients without RAS mutations), prospective-retrospective analysis | exploratoryDouillard 2013 | median 26 months | median 20.2 months | HR 0.78 (95% CI 0.62–0.99)P=0.04Prospective-retrospective analysis of PRIME by RAS (KRAS or NRAS) status; 512 patients without RAS mutations. Hazard ratio for death with panitumumab-FOLFOX4. |
| Endpoint | Analysis | Panitumumab plus FOLFOX4 | FOLFOX4 | Effect |
|---|---|---|---|---|
| PFSWild-type KRAS stratum (analysed on an intention-to-treat basis by tumour KRAS status, as stated in the abstract) | primaryDouillard 2010 | median 9.6 months | median 8 months | HR 0.80 (95% CI 0.66–0.97)P=0.02Hazard ratio for progression or death, panitumumab-FOLFOX4 versus FOLFOX4, in the wild-type KRAS stratum. The 2013 report describes the patients in this analysis as those without KRAS mutations in exon 2. |
| OSWild-type KRAS stratum (analysed on an intention-to-treat basis by tumour KRAS status, as stated in the abstract) | primaryDouillard 2010 | median 23.9 months | median 19.7 months | HR 0.83 (95% CI 0.67–1.02)P=0.072Secondary endpoint; the abstract calls the increase in overall survival nonsignificant. |
| PFSMutant KRAS stratum (analysed on an intention-to-treat basis by tumour KRAS status, as stated in the abstract) | exploratoryDouillard 2010 | — | — | HR 1.29 (95% CI 1.04–1.62)P=0.02Hazard ratio above 1 means shorter progression-free survival with panitumumab-FOLFOX4 than with FOLFOX4 in the mutant KRAS stratum. |
| OSMutant KRAS stratum (analysed on an intention-to-treat basis by tumour KRAS status, as stated in the abstract) | exploratoryDouillard 2010 | median 15.5 months | median 19.3 months | HR 1.24 (95% CI 0.98–1.57)P=0.068Secondary endpoint; the abstract gives the medians as 'respectively' after naming the panitumumab-FOLFOX4 and FOLFOX4 arms in that order. |
| PFSRAS wild-type (no KRAS or NRAS mutation; 512 patients without RAS mutations), prospective-retrospective analysis | exploratoryDouillard 2013 | median 10.1 months | median 7.9 months | HR 0.72 (95% CI 0.58–0.90)P=0.004Prospective-retrospective analysis of PRIME by RAS (KRAS or NRAS) status; 512 patients without RAS mutations. Hazard ratio for progression or death with panitumumab-FOLFOX4. |
| OSRAS wild-type (no KRAS or NRAS mutation; 512 patients without RAS mutations), prospective-retrospective analysis | exploratoryDouillard 2013 | median 26 months | median 20.2 months | HR 0.78 (95% CI 0.62–0.99)P=0.04Prospective-retrospective analysis of PRIME by RAS (KRAS or NRAS) status; 512 patients without RAS mutations. Hazard ratio for death with panitumumab-FOLFOX4. |
Data table
| Endpoint | HR | 95% CI |
|---|---|---|
| PFS | 0.8 | 0.66–0.97 |
| OS | 0.83 | 0.67–1.02 |
| PFS | 1.29 | 1.04–1.62 |
| OS | 1.24 | 0.98–1.57 |
| PFS | 0.72 | 0.58–0.9 |
| OS | 0.78 | 0.62–0.99 |
- Panitumumab plus FOLFOX4 (experimental)
- FOLFOX4 (control)
Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.
Data table (modelled values)
| Months | Panitumumab plus FOLFOX4 | FOLFOX4 |
|---|---|---|
| 0 | 100.0% | 100.0% |
| 6 | 64.8% | 59.5% |
| 12 | 42.0% | 35.4% |
| 18 | 27.3% | 21.0% |
| 24 | 17.7% | 12.5% |
- Panitumumab plus FOLFOX4 (experimental)
- FOLFOX4 (control)
Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.
Data table (modelled values)
| Months | Panitumumab plus FOLFOX4 | FOLFOX4 |
|---|---|---|
| 0 | 100.0% | 100.0% |
| 15 | 64.7% | 59.0% |
| 30 | 41.9% | 34.8% |
| 45 | 27.1% | 20.5% |
| 60 | 17.5% | 12.1% |
Appears in
Sources
Douillard JY, Siena S, Cassidy J, Tabernero J, Burkes R, Barugel M, et al. Randomized, phase III trial of panitumumab with infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX4) versus FOLFOX4 alone as first-line treatment in patients with previously untreated metastatic colorectal cancer: the PRIME study. J Clin Oncol. 2010;28(31):4697-705.
Douillard JY, Oliner KS, Siena S, Tabernero J, Burkes R, Barugel M, et al. Panitumumab-FOLFOX4 treatment and RAS mutations in colorectal cancer. N Engl J Med. 2013;369(11):1023-34.