Cetuximab as first-line monotherapy in patients with skin unresectable squamous cell carcinoma: Final results of a phase II multicenter study.

Abstract

8510 Background: Patients (pts) with advanced skin squamous cell carcinoma (SSCC) have a poor prognosis. The objective of the study was to evaluate single agent cetuximab (C) as first-line therapy for unresectable SCCS. Methods: Pts with advanced or metastatic EGFR expressing SCCS, ECOG PS ≤ 2 were eligible. No prior chemotherapy was allowed. C was kindly provided by Merck KGaA and administered iv weekly (400 mg/m2 initial dose followed by 250 mg/m2). Disease was evaluated by MRI or CT every 6 wks and independently assessed. Endpoints were disease control rate (DCR) at 6 wks, best objective response rate (ORR) (RECIST criteria) and toxicity, along with determination of KRAS mutations and FcγR genotypes. Statistical analyses were carried out both in the intent to treat (ITT) and per protocol (PP) populations. Results: Between Oct 2005 and Apr 2008, 36 pts were recruited: 58% were males, median age was 79 yrs (range 32-95), median PS was 1 (47%) and 72% of SCCS were AJCC stage 3; 31 pts were evaluable for tumor response and 36 for toxicity. DCR at 6 wks was 69% in the ITT population and 81% in the PP population (21 SD, 3 PR and 1 CR). Best ORR and DCR were 32% and 81% respectively in PP (15 SD, 8PR and 2 CR). Fourteen pts died: 6 due to disease progression; 4 were consideredas NOS and 3 sudden deaths were of unknown causes. Grade ¾ events were noted in 23 pts: infections (22%), nausea/vomiting (3%), anemia (4%), tumor bleeding (8%) and 4 C-related adverse events (2 grade 4 infusion reactions, 1 grade 3 interstitial pneumopathy and 1 grade 3 paronychia). Grade ½ acneiform rash occurred in 78% of pts. No KRAS mutation was identified in the 28 studied pts. In pts with FcγRIIa-131H/H and/or FcγRIIIa-158V/V genotypes, the PFS was similar in 131R and 158F carriers (5.4 vs. 3.5 mths; p = 0.34). Conclusions: Single agent C achieves 69% disease control rate as first-line treatment in pts with unresectable SCCS, therefore representing an interesting therapeutic option, especially in elderly pts. No significant financial relationships to disclose.