Hôpital Bichat, Service de Dermatologie, 46 rue Henri Huchard, Paris, cedex 75877, France.
J Clin Oncol. 2011 Sep 1;29(25):3419-26. doi: 10.1200/JCO.2010.34.1735. Epub 2011 Aug 1.
To evaluate the efficacy and safety of cetuximab, a monoclonal antibody that inhibits the epidermal growth factor receptor (EGFR), as a first-line monotherapy in patients with unresectable squamous cell carcinoma of the skin (SCCS).
Thirty-six patients received cetuximab (initial dose of 400 mg/m(2) followed by subsequent weekly doses of 250 mg/m(2)) for at least 6 weeks with a 48-week follow-up. The primary end point was the disease control rate (DCR) at 6 weeks (according to Response Evaluation Criteria in Solid Tumors [RECIST] criteria). Secondary end points included best response rate, overall survival, progression-free survival (PFS), and toxicity assessment. Association of treatment efficacy with RAS mutations or FcγR genotypes was investigated.
Median age of the study population was 79 years. DCR at 6 weeks was obtained in 25 of 36 patients (69%; 95% CI, 52% to 84%) of the intention-to-treat population. The best responses were eight partial responses and two complete responses. There were no cetuximab-related deaths. There were three related serious adverse events: two grade 4 infusion reactions and one grade 3 interstitial pneumopathy. Grade 1 to 2 acne-like rash occurred in 78% of patients and was associated with prolonged PFS. One HRAS mutation was identified. Combined FcγRIIa-131H/H and/or FcγRIIIa-158V/V polymorphisms were not associated with the clinical outcomes.
As a first-line treatment in patients with unresectable SCCS, cetuximab achieved 69% DCR. A randomized phase III trial is warranted to confirm that cetuximab may be considered as a therapeutic option especially in elderly patients. The low frequency of RAS mutations in SCCS makes SCCS tumors attractive for EGFR inhibition.
评估西妥昔单抗（一种抑制表皮生长因子受体（EGFR）的单克隆抗体）作为不可切除皮肤鳞状细胞癌（SCCS）患者一线单药治疗的疗效和安全性。
36 名患者接受西妥昔单抗（初始剂量 400mg/m²，随后每周剂量 250mg/m²）至少 6 周，并进行了 48 周的随访。主要终点是 6 周时的疾病控制率（DCR）（根据实体瘤反应评估标准[RECIST]标准）。次要终点包括最佳反应率、总生存率、无进展生存率（PFS）和毒性评估。还研究了治疗效果与 RAS 突变或 FcγR 基因型的关系。
研究人群的中位年龄为 79 岁。意向治疗人群中，25/36 例（69%；95%CI，52%至 84%）患者在 6 周时获得 DCR。最佳反应为 8 例部分缓解和 2 例完全缓解。没有与西妥昔单抗相关的死亡。有 3 例与治疗相关的严重不良事件：2 例 4 级输液反应和 1 例 3 级间质性肺炎。78%的患者出现 1 至 2 级痤疮样皮疹，与 PFS 延长有关。发现 1 个 HRAS 突变。FcγRIIa-131H/H 和/或 FcγRIIIa-158V/V 多态性的组合与临床结局无关。
作为不可切除 SCCS 患者的一线治疗方法，西妥昔单抗的 DCR 为 69%。需要进行随机 III 期试验以证实西妥昔单抗可能被视为一种治疗选择，特别是在老年患者中。SCCS 肿瘤中 RAS 突变的低频率使 EGFR 抑制成为 SCCS 肿瘤的一个有吸引力的治疗靶点。
