Bhatia Aarti, Mehra Ranee, Bauman Jessica, Khan Saad A, Wei Wei, Neumeister Veronique, Sandoval-Schaefer Teresa, Alpaugh R Katherine, Lango Miriam, Rimm David L, Ridge John A, Burtness Barbara
Department of Internal Medicine (Oncology), Yale School of Medicine and Yale Cancer Center, New Haven, Connecticut, USA.
Director of Head and Neck Medical Oncology and Professor of Medicine, Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland Medical Center, Baltimore, Maryland, USA.
Head Neck. 2025 Apr 1. doi: 10.1002/hed.28152.
Prognosis for patients with recurrent/metastatic (R/M) head and neck squamous cell cancer (HNSCC) remains poor. We hypothesized that the addition of an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) to standard therapy would improve responses by inhibiting nuclear translocation of EGFR and designed a phase 2 trial of chemotherapy, cetuximab, and erlotinib in patients with R/M HNSCC. A 24 patients were enrolled and treated with carboplatin, paclitaxel, and cetuximab administered in 21-day cycles. Erlotinib was added with cycle 2. The primary end point was the objective response rate (ORR). The secondary end points were toxicity, overall survival (OS) and laboratory correlates. Median age was 65.5 years. Median duration on treatment was 4.6 months. ORR with cycle 1 of treatment was 33.3%, and for cycle 2 and beyond was 58.3%. Median progression-free survival (PFS) was 6.2 months, and median OS was 10.6 months. Most common treatment-related adverse events included anemia, neutropenia, skin rash, diarrhea, and hypomagnesemia. Dual EGFR blockade was tolerable and efficacious in this small patient sample. With an ORR of 58.3%, the study met its primary endpoint. PFS and OS were comparable to historical controls. Dual EGFR targeting without the chemotherapy backbone is worthy of further study. Trail Registration: ClinicalTrials.gov identifier: NCT01316757.
复发性/转移性（R/M）头颈部鳞状细胞癌（HNSCC）患者的预后仍然很差。我们假设在标准治疗中添加表皮生长因子受体（EGFR）酪氨酸激酶抑制剂（TKI）可通过抑制EGFR的核转位来改善反应，并设计了一项针对R/M HNSCC患者的化疗、西妥昔单抗和厄洛替尼的2期试验。24例患者入组，接受以21天为周期给药的卡铂、紫杉醇和西妥昔单抗治疗。从第2周期开始添加厄洛替尼。主要终点是客观缓解率（ORR）。次要终点是毒性、总生存期（OS）和实验室相关指标。中位年龄为65.5岁。中位治疗持续时间为4.6个月。第1周期治疗的ORR为33.3%，第2周期及以后为58.3%。中位无进展生存期（PFS）为6.2个月，中位OS为10.6个月。最常见的治疗相关不良事件包括贫血、中性粒细胞减少、皮疹、腹泻和低镁血症。在这个小患者样本中，双重EGFR阻断是可耐受且有效的。ORR为58.3%，该研究达到了其主要终点。PFS和OS与历史对照相当。无化疗基础的双重EGFR靶向治疗值得进一步研究。试验注册：ClinicalTrials.gov标识符：NCT01316757。
