Zalutumumab plus best supportive care versus best supportive care alone in patients with recurrent or metastatic squamous-cell carcinoma of the head and neck after failure of platinum-based chemotherapy: An open-label, randomised phase III trial
The Lancet Oncology, 03/08/2011
Clinical Article
Machiels JP et al. – Zalutumumab did not increase overall survival in this study. Progression-free survival was extended in patients with recurrent squamous-cell carcinoma of the head and neck who had failed platinum-based chemotherapy. Zalutumumab dose titration on the basis of rash is safe.
Methods- In our open-label, parallel-group, phase 3, randomised trial
- Randomly allocated patients with squamous-cell carcinoma of head and neck regarded as incurable with standard therapy
- WHO performance status of 0—2, and progressive disease within 6 months of platinum-based therapy in 2:1 ratio to receive zalutumumab plus best supportive care (zalutumumab group) or best supportive care with optional methotrexate (control group) at medical centres in Europe, Brazil, and Canada
- Randomisation done via centralised interactive voice-response system, stratified by performance status
- Data analysed when randomisation code broken, after completion of accrual and cleaning of relevant data
- An independent review committee, masked to treatment assignment, assessed tumour response and disease progression according to response evaluation criteria in solid tumours
- Zalutumumab given weekly by individual dose titration on basis of skin rash
- After prespecified 231 deaths, included all randomised patients in survival analyses and all patients receiving at least 1 session of therapy in safety analysis
- Primary endpoint OS, although PFS also assessed
- randomly allocated 191 (67%) of 286 eligible patients to the zalutumumab group and 95 (33%) to the control group
- Median OS 6·7 months (95% CI 5·8—7·0) in the zalutumumab group and 5·2 months (4·1—6·4) in the control group (hazard ratio [HR] for death, stratified by WHO performance status, was 0·77, 97·06% CI 0·57—1·05; unadjusted p=0·0648)
- PFS longer in zalutumumab group than in control group (HR for progression or death, stratified by WHO performance status, was 0·63, 95% CI 0·47—0·84; p=0·0012)
- 189 patients given zalutumumab and 94 controls were included in the safety analysis
- Most common grade 3—4 AE were rash (39 [21%] patients in zalutumumab group vs none in control group), anaemia (11 [6%] vs 5 [5%]), and pneumonia (nine [5%] vs two [2%])
- 28 (15%) patients in the zalutumumab group had grade 3/4 infections compared with eight (9%) in the control group
- Most common serious AE were tumour haemorrhage (28 [15%] patients given zalutumumab vs 13 [14%] controls), pneumonia (13 [7%] vs 3 [3%]), and dysphagia (11 [6%] vs 2 [2%])
