Table 1.
Selected Phase II and III trials of cetuximab in LA HNSCC
| Trial | Phase | Sample size | Study population | Treatment regimen | Primary endpoint | Results |
|---|---|---|---|---|---|---|
| Definitive RT or CRT | ||||||
| Bonner et al36,37 | III | 424 (213 in Arm A, 211 in Arm B) |
Stage III–IV Untreated Oropharynx, larynx, hypopharynx |
Arm A: RT alone Arm B: RT + cetuximab |
LRC | • LRC: Arm A, 24.4 months; Arm B, 14.9 months (HR, 0.68; P=0.005) • Median OS: Arm A, 49.0 months; Arm B, 29.3 months (HR, 0.74; 95% CI, 0.57–0.97; P=0.03) • 5-year OS: Arm A, 36.4%; Arm B, 45.6% (HR, 0.73; 95% CI, 0.56–0.95; P=0.018) • Distant control: no significant differences • Toxicity: apart from rash and infusion reactions, no difference in rate of grade ≥3 toxicities |
| RTOG 052239 | III | 891 (444 in Arm A, 447 in Arm B) |
Stage III–IV Untreated Oropharynx, larynx, hypopharynx |
Arm A: cetuximab + treatment in Arm B Arm B: bolus cisplatin ×2 cycles + RT |
PFS | • PFS: HR (Arm A/B), 1.08; 95% CI, 0.88–1.32; P=0.76 • OS: HR (Arm A/B), 0.95; 95% CI, 0.74–1.21; P=0.32 • LRF: HR (Arm A/B), 1.30; 95% CI, 0.99–1.70; P=0.97 • Toxicity: higher rates in Arm A for grade 3–4 mucositis (Arm A, 43%; Arm B, 33%; P=0.002), skin reaction (20% vs 1%; P<0.001), fatigue (14% vs 9%; P=0.03), anorexia (16% vs 11%; P=0.04), hypokalemia (10% vs 5%; P=0.005) |
| Adjuvant CRT | ||||||
| RTOG 0234102 | II | 203 (97 in Arm A, 106 in Arm B) |
High-risk resected HNSCC 94% stage IV 47% oral cavity |
Arm A: RT + cisplatin and cetuximab Arm B: RT + docetaxel and cetuximab |
DFS | • 2-year DFS: Arm A, 57% (95% CI, 47–67); Arm B, 66% (95% CI, 56–75) • 2-year OS: Arm A, 69% (95% CI, 60–79); Arm B, 79% (95% CI, 71–87) • 2-year distant metastases: Arm A, 26% (95% CI, 17–35); Arm B, 13% (95% CI, 7–20) • Toxicity: similar in both arms |
| Adjuvant RT | ||||||
| Mesia et al103 | II | 91 (45 in Arm A, 46 in Arm B) |
Stage III, IVA–B Untreated Oropharynx |
Arm A: RT + cetuximab Arm B: RT + cetuximab, then 12 weeks of cetuximab maintenance |
LRC | • LRC at 1 year: Arm A, 59%; Arm B, 47% (P=0.25) • LRC at 2 years: 44% for both arms • Toxicity: comparable between arms |
| Induction chemotherapy, then concurrent CRT | ||||||
| TREMPLIN40 | II | 116 (60 in Arm A, 56 in Arm B) |
Stage III, IVA–B Untreated Larynx, hypopharynx |
IC with TPF Responders (≥50% response) randomized to Arm A: RT + cisplatin (bolus ×3 cycles) Arm B: RT + cetuximab |
LP | • LP: Arm A, 95% (95% CI, 86–98); Arm B, 93% (95% CI, 83–97) • OS at 18 months: Arm A, 92% (95% CI, 82–96); Arm B, 89% (95% CI, 79–95) • LFP: Arm A, 87% (95% CI, 76–93); Arm B, 82% (95% CI, 70–90) • Despite a higher rate of local failures in Arm B, more salvage laryngectomies were performed and resulted in similar ultimate locoregional failure rates (13.3% in Arm A, 10.7% in Arm B) • Toxicity: no difference in grade 3 or 4 mucositis; more grade 3 or 4 in-field dermatitis seen in Arm B (57%) vs Arm A (26%) |
| ECOG 1308104,105 | II | 80 (59 in Arm A, 21 in Arm B) | Stage III, IVA–B Untreated Oropharynx, HPV positive |
IC with paclitaxel + cisplatin + cetuximab If clinical CR → Arm A: low-dose IMRT + cetuximab or If PR/SD → Arm B: standard IMRT + cetuximab |
2-year PFS | • Complete RR to IC: 63.8% (central review), 71.3% (investigator reported), with 59/80 patients receiving low-dose IMRT + cetuximab in Arm A • Overall RR: 86% (14% unevaluable) • Rate of posttreatment neck dissection: 13.4% (low-dose IMRT) vs 22.2% (standard IMRT); P=0.46 |
| Induction chemotherapy, then risk-based local therapy | ||||||
| Massarelli et al106 | II | 136 | Stage IVA-B Untreated Oropharynx, oral cavity, larynx, hypopharynx, nasopharynx |
Arm A: paclitaxel + carboplatin + cetuximab Arm B: TPF + cetuximab; each followed by risk-based local therapy, defined by HPV status and stage, and stratification by smoking status |
2-year PFS | • Overall RR to IC: Arm A, 78%; Arm B, 82% • Overall RR after local therapy: Arm A, 94%; Arm B, 85% • 2-year PFS: Arm A, 89%; Arm B, 80% |
Abbreviations: LA, locally advanced; HNSCC, head and neck squamous cell carcinoma; RT, radiation therapy; CRT, chemoradiation therapy; LRC, locoregional control; HR, hazard ratio; OS, overall survival; CI, confidence interval; PFS, progression-free survival; LRF, locoregional failure; DFS, disease-free survival; IC, induction chemotherapy; TPF, docetaxel/cisplatin/5-fluorouracil; LP, larynx preservation; LFP, larynx function preservation; HPV, human papillomavirus; CR, complete response; IMRT, intensity-modulated radiation therapy; RR, response rate; PR, partial response; SD, stable disease.