阿法替尼作为复发性/转移性头颈部鳞状细胞癌二线治疗药物：LUX-Head and Neck 1 试验中治疗依从性、安全性和阿法替尼给药方式的亚组分析。

Afatinib as second-line treatment in patients with recurrent/metastatic squamous cell carcinoma of the head and neck: Subgroup analyses of treatment adherence, safety and mode of afatinib administration in the LUX-Head and Neck 1 trial.

机构信息

Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School and Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.

Centre Antoine Lacassagne, FHU OncoAge, Université Côte d'Azur, Nice, France.

出版信息

Oral Oncol. 2019 Oct;97:82-91. doi: 10.1016/j.oraloncology.2019.08.004. Epub 2019 Aug 23.

DOI:10.1016/j.oraloncology.2019.08.004

PMID:31450171

Abstract

OBJECTIVES

Patients with head and neck squamous cell carcinoma (HNSCC) can experience severe symptom burden and/or difficulty swallowing, leading to problems with treatment adherence/administration. In LUX-Head and Neck 1 (LH&N1; NCT01345682), second-line afatinib improved progression-free survival (PFS) versus methotrexate in patients with recurrent/metastatic HNSCC. We report adherence and safety across pre-specified and additional subgroups potentially linked to afatinib PFS benefit in LH&N1 (p16 status, smoking history), and afatinib adherence, safety and efficacy by administration (oral versus feeding tube; post-hoc analysis).

METHODS

Patients were randomized (2:1) to afatinib (40 mg/day) or intravenous methotrexate (40 mg/m/week).

RESULTS

Among 320 afatinib-treated and 160 methotrexate-treated patients, 83-92% and 76-92% (of patients with data available) across all subgroups took ≥80% of treatment. Across p16 status and smoking history subgroups, the most common treatment-related adverse events (AEs) were diarrhea (70-91%), rash/acne (72-84%), stomatitis (34-73%) with afatinib; and included stomatitis (39-100%), fatigue (22-50%), nausea (19-36%) with methotrexate. Dose reduction decreased AE incidence/severity. Baseline characteristics were generally similar between oral/feeding tube (n = 276/n = 46) groups. 89%/89% (of patients with data available) took ≥80% of assigned afatinib. Median PFS was 2.6 versus 2.7 months (hazard ratio: 0.997; 95% confidence interval: 0.72-1.38). The most common afatinib-related AEs were: rash/acne (74% versus 74%), diarrhea (73% versus 65%), stomatitis (40% versus 30%).

CONCLUSION

Subgroup analyses of LH&N1 demonstrate that afatinib has predictable and manageable safety across patient subgroups, with high treatment adherence, and is effective via oral and feeding tube administration.

摘要

目的

头颈部鳞状细胞癌（HNSCC）患者可能会经历严重的症状负担和/或吞咽困难，从而导致治疗依从性/管理出现问题。在 LUX-Head and Neck 1（LH&N1；NCT01345682）中，二线阿法替尼与甲氨蝶呤相比，改善了复发性/转移性 HNSCC 患者的无进展生存期（PFS）。我们报告了在 LH&N1 中（p16 状态、吸烟史）与阿法替尼 PFS 获益相关的预先指定和其他亚组以及阿法替尼依从性、安全性和疗效（口服与经饲管；事后分析）的安全性。

方法

患者以 2:1 的比例随机分配至阿法替尼（40mg/天）或静脉注射甲氨蝶呤（40mg/m/周）。

结果

在 320 名接受阿法替尼治疗和 160 名接受甲氨蝶呤治疗的患者中，所有亚组中均有 83%-92%和 76%-92%（有数据可用的患者）接受了至少 80%的治疗。在 p16 状态和吸烟史亚组中，最常见的治疗相关不良事件（AE）是腹泻（70%-91%）、皮疹/痤疮（72%-84%）、口腔炎（34%-73%）用阿法替尼；包括口腔炎（39%-100%）、疲劳（22%-50%）、恶心（19%-36%）用甲氨蝶呤。减少剂量可降低 AE 的发生率/严重程度。口服/饲管（n=276/n=46）组之间的基线特征通常相似。89%/89%（有数据可用的患者）接受了至少 80%的阿法替尼治疗。中位 PFS 为 2.6 个月与 2.7 个月（风险比：0.997；95%置信区间：0.72-1.38）。最常见的阿法替尼相关 AE 是：皮疹/痤疮（74%与 74%）、腹泻（73%与 65%）、口腔炎（40%与 30%）。