ASPECCT
Panitumumab versus cetuximab in patients with chemotherapy-refractory wild-type KRAS exon 2 metastatic colorectal cancer (ASPECCT): a randomised, multicentre, open-label, non-inferiority phase 3 study
Phase 3N = 1,010NCT01001377
- Population
- Adults aged 18 or older with chemotherapy-refractory metastatic colorectal cancer, ECOG performance status 2 or less and wild-type KRAS exon 2 status; 1010 randomised, 999 started treatment (499 panitumumab, 500 cetuximab).
- Design
- Randomised (1:1; computer-generated sequence, permuted blocks, stratified by geographical region and ECOG performance status), multicentre, open-label phase 3 non-inferiority study at centres in North America, South America, Europe, Asia, Africa and Australia. Patients received panitumumab 6 mg/kg once every 2 weeks or cetuximab (400 mg/m2 initial dose, then 250 mg/m2 once a week). Primary endpoint overall survival, assessed for non-inferiority: retention of at least 50% of the cetuximab treatment effect, using a historical hazard ratio of 0.55 for cetuximab plus best supportive care versus best supportive care alone. The primary analysis included patients who received one or more dose of study drug, analysed per allocated treatment. Enrolment from 2 February 2010 to 19 July 2012. The final analysis followed patients for survival for 24 months after the last patient was randomised, without formal hypothesis testing.
- Primary endpoint
- OS
- Arms
- Panitumumab (experimental, n = 499): Panitumumab 6 mg/kg once every 2 weeks
- Cetuximab (control, n = 500): Cetuximab 400 mg/m2 initial dose, then 250 mg/m2 once a week
- People
- Price TJ
OSHR 0.97 (95% CI 0.84–1.11)Δ median OS+0.4 monthsOSHR 0.94 (95% CI 0.82–1.07)Δ median OS+0.3 monthsPFSHR 0.98 (95% CI 0.87–1.12)Δ median PFS−0.2 months
Show the numbers
| Endpoint | Analysis | Panitumumab | Cetuximab | Effect |
|---|---|---|---|---|
| OSPatients who received one or more dose of panitumumab or cetuximab, analysed per allocated treatment (499 and 500)Overall survival, assessed for non-inferiority of panitumumab to cetuximab (primary endpoint) | primaryPrice 2014 | median 10.4 months (9.4–11.6) | median 10 months (9.3–11.0) | HR 0.97 (95% CI 0.84–1.11)P=0.0007The P value is for the non-inferiority test (Z score -3.19), not for a difference between the arms. Panitumumab retained 105.7% (95% CI 81.9 to 129.5) of the effect of cetuximab on overall survival seen in this study. |
| OSPatients randomised who received at least one treatment dose (499 panitumumab, 500 cetuximab)Overall survival, final analysis (24 months of survival follow-up after the last patient was randomised) | finalPrice 2016 | median 10.2 months | median 9.9 months | HR 0.94 (95% CI 0.82–1.07)No formal hypothesis testing was done in the final analysis (abstract); the authors conclude that it is consistent with non-inferiority in the primary analysis. Follow-up for survival continued for 24 months after the last patient was randomised. |
| PFSPatients randomised who received at least one treatment dose (499 panitumumab, 500 cetuximab)Progression-free survival, final analysis | finalPrice 2016 | median 4.2 months | median 4.4 months | HR 0.98 (95% CI 0.87–1.12)Secondary endpoint; no formal hypothesis testing was done in the final analysis. |
| Endpoint | Analysis | Panitumumab | Cetuximab | Effect |
|---|---|---|---|---|
| OSPatients who received one or more dose of panitumumab or cetuximab, analysed per allocated treatment (499 and 500)Overall survival, assessed for non-inferiority of panitumumab to cetuximab (primary endpoint) | primaryPrice 2014 | median 10.4 months (9.4–11.6) | median 10 months (9.3–11.0) | HR 0.97 (95% CI 0.84–1.11)P=0.0007The P value is for the non-inferiority test (Z score -3.19), not for a difference between the arms. Panitumumab retained 105.7% (95% CI 81.9 to 129.5) of the effect of cetuximab on overall survival seen in this study. |
| OSPatients randomised who received at least one treatment dose (499 panitumumab, 500 cetuximab)Overall survival, final analysis (24 months of survival follow-up after the last patient was randomised) | finalPrice 2016 | median 10.2 months | median 9.9 months | HR 0.94 (95% CI 0.82–1.07)No formal hypothesis testing was done in the final analysis (abstract); the authors conclude that it is consistent with non-inferiority in the primary analysis. Follow-up for survival continued for 24 months after the last patient was randomised. |
| PFSPatients randomised who received at least one treatment dose (499 panitumumab, 500 cetuximab)Progression-free survival, final analysis | finalPrice 2016 | median 4.2 months | median 4.4 months | HR 0.98 (95% CI 0.87–1.12)Secondary endpoint; no formal hypothesis testing was done in the final analysis. |
Data table
| Endpoint | HR | 95% CI |
|---|---|---|
| OS | 0.97 | 0.84–1.11 |
| OS | 0.94 | 0.82–1.07 |
| PFS | 0.98 | 0.87–1.12 |
- Panitumumab (experimental)
- Cetuximab (control)
Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.
Data table (modelled values)
| Months | Panitumumab | Cetuximab |
|---|---|---|
| 0 | 100.0% | 100.0% |
| 7 | 62.7% | 61.6% |
| 13 | 42.0% | 40.6% |
| 20 | 26.4% | 25.0% |
| 26 | 17.7% | 16.5% |
- Panitumumab (experimental)
- Cetuximab (control)
Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.
Data table (modelled values)
| Months | Panitumumab | Cetuximab |
|---|---|---|
| 0 | 100.0% | 100.0% |
| 6 | 66.5% | 65.7% |
| 13 | 41.3% | 40.2% |
| 19 | 27.5% | 26.4% |
| 26 | 17.1% | 16.2% |
Appears in
Sources
Price TJ, Peeters M, Kim TW, Li J, Cascinu S, Ruff P, et al. Panitumumab versus cetuximab in patients with chemotherapy-refractory wild-type KRAS exon 2 metastatic colorectal cancer (ASPECCT): a randomised, multicentre, open-label, non-inferiority phase 3 study. Lancet Oncol. 2014;15(6):569-79.
Price T, Kim TW, Li J, Cascinu S, Ruff P, Suresh AS, et al. Final results and outcomes by prior bevacizumab exposure, skin toxicity, and hypomagnesaemia from ASPECCT: randomized phase 3 non-inferiority study of panitumumab versus cetuximab in chemorefractory wild-type KRAS exon 2 metastatic colorectal cancer. Eur J Cancer. 2016;68:51-59.