of age or older.
The use of cetuximab in combination with chemo-radiotherapy has so far not been adequately investigated. Thus, a benefit-risk ratio for this combination has not yet been established.
Cetuximab in combination with platinum-based chemotherapy in recurrent and/or metastatic disease
• EMR 62 202-002: This randomised study in patients with recurrent and/or metastatic squamous cell cancer of the head and neck who had not received prior chemotherapy for this disease compared the combination of cetuximab and cisplatin or carboplatin plus infusional 5-fluorouracil (222 patients) to the same chemotherapy alone (220 patients). Treatment in the cetuximab arm consisted of up to 6 cycles of platinum-based chemotherapy in combination with cetuximab followed by cetuximab as maintenance therapy until disease progression.
The efficacy data generated in this study are summarised in the table below:
|
Variable/ statistic
|
Cetuximab + CTX
(N=222)
|
CTX
(N=220)
|
|
OS
|
|
|
|
months, median (95% CI)
|
10.1 (8.6, 11.2)
|
7.4 (6.4, 8.3)
|
|
Hazard Ratio (95% CI)
|
0.797 (0.644, 0.986)
|
|
p-value
|
0.0362
|
|
PFS
|
|
|
|
months, median (95% CI)
|
5.6 (5.0, 6.0)
|
3.3 (2.9, 4.3)
|
|
Hazard Ratio (95% CI)
|
0.538 (0.431, 0.672)
|
|
p-value
|
<0.0001
|
|
ORR
|
|
|
|
% (95% CI)
|
35.6 (29.3, 42.3)
|
19.5 (14.5, 25.4)
|
|
p-value
|
0.0001
|
CI = confidence interval, CTX = platinum-based chemotherapy, ORR = objective response rate, OS = overall survival time, PFS = progression-free survival time
Patients with a good prognosis as indicated by tumour stage, Karnofsky performance status (KPS) and age had a more pronounced benefit, when cetuximab was added to platinum-based chemotherapy. In contrast to progression free survival time, no benefit in overall survival time could be demonstrated in patients with KPS 80 who were 65 years of age or older.
Paediatric population
The European Medicines Agency has waived the obligation to submit the results of studies with cetuximab in all subsets of the paediatric population in the granted indications (see section 4.2 for information on paediatric use).
5.2 Pharmacokinetic properties
Cetuximab pharmacokinetics were studied when cetuximab was administered as monotherapy or in combination with concomitant chemotherapy or radiation therapy in clinical studies. Intravenous infusions of cetuximab exhibited dose-dependent pharmacokinetics at weekly doses ranging from 5 to 500 mg/m2 body surface area.
When cetuximab was administered at an initial dose of 400 mg/m2 body surface area, the mean volume of distribution was ap
