Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck
Phase 3
- Population
- Locoregionally advanced squamous-cell carcinoma of the head and neck (oropharynx, hypopharynx or larynx)
- Design
- Multinational, randomised, unblinded study of locoregionally advanced squamous-cell carcinoma of the oropharynx, hypopharynx or larynx with measurable disease: high-dose radiotherapy alone (213 patients) or with weekly cetuximab (211 patients) at an initial dose of 400 mg per square metre of body-surface area, then 250 mg per square metre weekly for the duration of radiotherapy. Randomised 1:1 with adaptive minimisation (Karnofsky score, T stage, N stage, radiation fractionation). Primary end point: duration of locoregional control.
- Primary endpoint
- Locoregional control
- Arms
- Radiotherapy alone (control, n = 213): High-dose radiotherapy for 6-7 weeks
- Radiotherapy plus cetuximab (experimental, n = 211): High-dose radiotherapy plus weekly cetuximab: 400 mg per square metre initial dose, then 250 mg per square metre weekly
- People
- Bonner JA
Locoregional controlHR 0.68Δ median Locoregional control+9.5 monthsOSHR 0.74Δ median OS+19.7 monthsPFSHR 0.7OSHR 0.73 (95% CI 0.56–0.95)
Show the numbers
| Endpoint | Analysis | Radiotherapy plus cetuximab | Radiotherapy alone | Effect |
|---|---|---|---|---|
| Locoregional controlRandomised patients (213 and 211); analysis population not stated in the 2006 abstract | primaryBonner 2006 | median 24.4 months | median 14.9 months | HR 0.68P=0.005Median duration of locoregional control; the hazard ratio is for locoregional progression or death. |
| OSRandomised patients (213 and 211); analysis population not stated in the 2006 abstract | primarymedian follow-up 54 monthsBonner 2006 | median 49 months | median 29.3 months | HR 0.74P=0.03 |
| PFSRandomised patients (213 and 211); analysis population not stated in the 2006 abstract | primarymedian follow-up 54 monthsBonner 2006 | — | — | HR 0.7P=0.006 |
| OSIntention-to-treat | long term-updateBonner 2010 | median 49 months (32.8–69.5); 45.6% at 5 y | median 29.3 months (20.6–41.4); 36.4% at 5 y | HR 0.73 (95% CI 0.56–0.95)P=0.018 |
| OSCetuximab-treated patients with acneiform rash of grade 2 or worse compared with no rash or grade 1 rash | exploratoryBonner 2010 | — | — | HR 0.49 (95% CI 0.34–0.72)P=0.002Association between rash and survival within the cetuximab arm; not a randomised comparison. |
| Endpoint | Analysis | Radiotherapy plus cetuximab | Radiotherapy alone | Effect |
|---|---|---|---|---|
| Locoregional controlRandomised patients (213 and 211); analysis population not stated in the 2006 abstract | primaryBonner 2006 | median 24.4 months | median 14.9 months | HR 0.68P=0.005Median duration of locoregional control; the hazard ratio is for locoregional progression or death. |
| OSRandomised patients (213 and 211); analysis population not stated in the 2006 abstract | primarymedian follow-up 54 monthsBonner 2006 | median 49 months | median 29.3 months | HR 0.74P=0.03 |
| PFSRandomised patients (213 and 211); analysis population not stated in the 2006 abstract | primarymedian follow-up 54 monthsBonner 2006 | — | — | HR 0.7P=0.006 |
| OSIntention-to-treat | long term-updateBonner 2010 | median 49 months (32.8–69.5); 45.6% at 5 y | median 29.3 months (20.6–41.4); 36.4% at 5 y | HR 0.73 (95% CI 0.56–0.95)P=0.018 |
| OSCetuximab-treated patients with acneiform rash of grade 2 or worse compared with no rash or grade 1 rash | exploratoryBonner 2010 | — | — | HR 0.49 (95% CI 0.34–0.72)P=0.002Association between rash and survival within the cetuximab arm; not a randomised comparison. |
Data table
| Endpoint | HR | 95% CI |
|---|---|---|
| OS | 0.73 | 0.56–0.95 |
| OS | 0.49 | 0.34–0.72 |
- Radiotherapy plus cetuximab (experimental)
- Radiotherapy alone (control)
Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.
Data table (modelled values)
| Months | Radiotherapy plus cetuximab | Radiotherapy alone |
|---|---|---|
| 0 | 100.0% | 100.0% |
| 15 | 65.3% | 49.8% |
| 31 | 41.5% | 23.6% |
| 46 | 27.1% | 11.8% |
| 61 | 17.7% | 5.9% |
- Radiotherapy plus cetuximab (experimental)
- Radiotherapy alone (control)
Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.
Data table (modelled values)
| Months | Radiotherapy plus cetuximab | Radiotherapy alone |
|---|---|---|
| 0 | 100.0% | 100.0% |
| 31 | 64.5% | 48.0% |
| 61 | 42.2% | 23.6% |
| 92 | 27.2% | 11.3% |
| 123 | 17.6% | 5.4% |
Appears in
Sources
Bonner JA, Harari PM, Giralt J, Azarnia N, Shin DM, Cohen RB, et al. Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck. N Engl J Med. 2006;354(6):567-78.
Bonner JA, Harari PM, Giralt J, Cohen RB, Jones CU, Sur RK, et al. Radiotherapy plus cetuximab for locoregionally advanced head and neck cancer: 5-year survival data from a phase 3 randomised trial, and relation between cetuximab-induced rash and survival. Lancet Oncol. 2010;11(1):21-8.