RTOG 1016
Radiotherapy plus cetuximab or cisplatin in human papillomavirus-positive oropharyngeal cancer (NRG Oncology RTOG 1016): a randomised, multicentre, non-inferiority trial
Phase 3N = 849NCT01302834
- Population
- HPV-positive oropharyngeal squamous cell carcinoma (AJCC 7th edition T1-T2 N2a-N3 or T3-T4 N0-N3, M0), Zubrod performance status 0 or 1
- Design
- Randomised, multicentre non-inferiority trial at 182 centres in the USA and Canada: 987 patients enrolled, 849 randomised 1:1 to radiotherapy plus cetuximab (425) or radiotherapy plus cisplatin (424). All received accelerated IMRT, 70 Gy in 35 fractions over 6 weeks. Cetuximab 400 mg per square metre loading dose then 250 mg per square metre weekly for seven doses; cisplatin 100 mg per square metre on days 1 and 22. Primary endpoint OS with non-inferiority margin 1.45; primary analysis in the modified intention-to-treat population of eligible patients (399 cetuximab, 406 cisplatin).
- Primary endpoint
- OS
- Arms
- Radiotherapy plus cisplatin (control, n = 424): IMRT 70 Gy in 35 fractions over 6 weeks plus cisplatin 100 mg per square metre on days 1 and 22
- Radiotherapy plus cetuximab (experimental, n = 425): IMRT 70 Gy in 35 fractions over 6 weeks plus cetuximab 400 mg per square metre loading dose then 250 mg per square metre weekly for seven doses
- People
- Gillison ML, NRG Oncology
OSHR 1.45Δ 60-month OS−6.7 pointsPFSHR 1.72 (95% CI 1.29–2.29)Δ 60-month PFS−11.1 pointsLocoregional failureHR 2.05 (95% CI 1.35–3.10)Δ 60-month Locoregional failure+7.4 points
Show the numbers
| Endpoint | Analysis | Radiotherapy plus cetuximab | Radiotherapy plus cisplatin | Effect |
|---|---|---|---|---|
| OSEligible patients, modified intention-to-treat (399 cetuximab, 406 cisplatin) | primarymedian follow-up 4.5 yearsGillison 2019 | 77.9% at 5 y (73.4–82.5%) | 84.6% at 5 y (80.6–88.6%) | HR 1.45P=0.5056 for non-inferiorityNon-inferiority margin 1.45. The hazard ratio of 1.45 is for cetuximab versus cisplatin (78 vs 55 deaths in the full text), with a one-sided 95% upper confidence limit of 1.94; the full text also gives a two-sided 95% CI of 1.03 to 2.05 and one-sided log-rank p=0.0163. |
| PFSEligible patients, modified intention-to-treat (399 cetuximab, 406 cisplatin) | primarymedian follow-up 4.5 yearsGillison 2019 | 67.3% at 5 y (62.4–72.2%) | 78.4% at 5 y (73.8–83.0%) | HR 1.72 (95% CI 1.29–2.29)P=0.0002 |
| Locoregional failureEligible patients, modified intention-to-treat (399 cetuximab, 406 cisplatin) | primarymedian follow-up 4.5 yearsGillison 2019 | 17.3% at 5 y (13.7–21.4%) | 9.9% at 5 y (6.9–13.6%) | HR 2.05 (95% CI 1.35–3.10) |
| Endpoint | Analysis | Radiotherapy plus cetuximab | Radiotherapy plus cisplatin | Effect |
|---|---|---|---|---|
| OSEligible patients, modified intention-to-treat (399 cetuximab, 406 cisplatin) | primarymedian follow-up 4.5 yearsGillison 2019 | 77.9% at 5 y (73.4–82.5%) | 84.6% at 5 y (80.6–88.6%) | HR 1.45P=0.5056 for non-inferiorityNon-inferiority margin 1.45. The hazard ratio of 1.45 is for cetuximab versus cisplatin (78 vs 55 deaths in the full text), with a one-sided 95% upper confidence limit of 1.94; the full text also gives a two-sided 95% CI of 1.03 to 2.05 and one-sided log-rank p=0.0163. |
| PFSEligible patients, modified intention-to-treat (399 cetuximab, 406 cisplatin) | primarymedian follow-up 4.5 yearsGillison 2019 | 67.3% at 5 y (62.4–72.2%) | 78.4% at 5 y (73.8–83.0%) | HR 1.72 (95% CI 1.29–2.29)P=0.0002 |
| Locoregional failureEligible patients, modified intention-to-treat (399 cetuximab, 406 cisplatin) | primarymedian follow-up 4.5 yearsGillison 2019 | 17.3% at 5 y (13.7–21.4%) | 9.9% at 5 y (6.9–13.6%) | HR 2.05 (95% CI 1.35–3.10) |
Data table
| Endpoint | HR | 95% CI |
|---|---|---|
| PFS | 1.72 | 1.29–2.29 |
| Locoregional failure | 2.05 | 1.35–3.1 |