A randomized, phase 2 study of cetuximab plus cisplatin with or without paclitaxel for the first-line treatment of patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck.

B490 (EudraCT# 2011-002564-24) is a randomized, phase 2b, noninferiority study investigating the efficacy and safety of first-line cetuximab plus cisplatin with/without paclitaxel (CetCis versus CetCisPac) in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN).

Eligible patients had confirmed R/M SCCHN (oral cavity/oropharynx/larynx/hypopharynx/paranasal sinus) and no prior therapy for R/M disease. Cetuximab was administered on day 1 (2-h infusion, 400mg/m²), then weekly (1-h infusions, 250mg/m²). Cisplatin was given as a 1-h infusion (CetCis arm: 100mg/m²; CetCisPac arm: 75mg/m²) on day 1 of each cycle for a maximum of six cycles. Paclitaxel was administered as a 3-h infusion (175mg/m²) on day 1 of each cycle. After six cycles, maintenance cetuximab was administered until disease progression or unacceptable toxicity. The primary end point was progression-free survival (PFS). We assumed a noninferiority margin of 1.40 as compatible with efficacy.

A total of 201 patients were randomized 1 : 1 to each regimen; 191 were assessable. PFS with CetCis (median, 6months) was noninferior to PFS with CetCisPac (median, 7months) [HR for CetCis versus CetCisPac 0.99; 95% CI: 0.72-1.36,P=0.906; margin of noninferiority (90% CI of 1.4) not reached]. Median overall survival was 13 versus 11months (HR=0.77; 95% CI: 0.53-1.11,P=0.117). The overall response rates were 41.8% versus 51.7%, respectively (OR=0.69; 95% CI: 0.38-1.20,P=0.181). Grade≥3 adverse event rates were 76% and 73% for CetCis versus CetCisPac, respectively, while grade 4 toxicities were lower in the two-drug versus three-drug arm (14% versus 33%,P=0.015). No toxic death or sepsis were reported and cardiac events were negligible (1%).The two-drug CetCis regimen proved to be noninferior in PFS to a three-drug combination with CetCisPac. The median OS of both regimens is comparable with that observed in EXTREME, while the life-threatening toxicity rate appeared reduced.EudraCT# 2011-002564-24.