TABLE 1.

Selection of de-escalation trials with reported outcomes: primary chemoradiation: substitution of cisplatin (cis) with cetuximab (cetux).

Study name, ID	AJCC, HPV, smoking	Design and primary endpoint	Adverse events	Survival outcomes
De-ESCALATE NCT01874171 (n = 334) Phase III	7th AJCC: T3T4-N0; T1N1-T4N3 8th AJCC:I, II, III HPV testing p16-IHC HPVDNA ISHSmoking<10py	Design: 70 Gy RT + cetuximab vs. cisplatin (100 mg/m2). Primary endpoint: overall acute and late severe toxicity	Cetux vs. cis: 2 years number of grade 3–5 events per patient: 4.82 vs. 4.81 (p = 0.98)	Cetux vs. cis: 2 years OS: 89.4 vs. 97.5%, p = 0.0007 2 year LR: 12 vs. 3%, p = 0.0026 2 yearr DM: 9 vs. 3% p = 0.0092
RTOG 1016 Phase III, n = 987	7th AJCC: T3N0-T4N0; T1T2-N2aN3 8th AJCCI, II, III HPV testing: p16-IHC Smoking<10py	Design: 70 Gy accelerated RT + cetuximab vs cisplatin (100 mg/m2). Primary endpoint: 5-year OS (non-inferiority)	Cetuximab vs. cisplatin: no difference in overall rates of acute events (p = 0.16); lower mean number of events per patient (2.35 vs. 3.19, p < 0.001); no difference in overall rates of late events (p = 0.19) or mean number (p = 0.12)	Cetux vs. cis: 5 years OS: 77.% vs. 84.6%, p = 0.016 5 years LR: 17.3 vs. 9.9%, p = 0.0005 5 years DM: 11.7 vs. 8.7%, p = 0.09