Kim Edward S, Halmos Balazs, Kohut Ingrid F, Patel Taral, Rostorfer Regan D, Spira Alexander I, Cseh Agnieszka, McKay John, Wallenstein Gudrun, Mileham Kathryn F
Department of Solid Tumor Oncology and Investigational Therapeutics, Levine Cancer Institute, Carolinas HealthCare System, Charlotte, NC USA.
Division of Hematology/Oncology, Columbia University, New York, NY USA.
Oncol Ther. 2017;5(1):103-110. doi: 10.1007/s40487-017-0043-5. Epub 2017 Apr 10.
Afatinib is an oral, irreversible ErbB family blocker approved for first-line treatment of metastatic epidermal growth factor receptor () mutation-positive non-small cell lung cancer (NSCLC). The expanded access program (EAP) allowed early access to afatinib and provided additional data on its safety, tolerability, and efficacy.
The afatinib EAP was an open-label, multicenter, single-arm program in the United States that treated and followed patients with locally advanced or metastatic NSCLC harboring mutations. Afatinib 40 mg was administered orally once daily until discontinuation due to disease progression, adverse events (AEs), or transition to commercially available drug.
Three hundred twenty-two patients received ≥1 dose of afatinib. Most patients had received prior therapies. Drug-related AEs occurred in 89.4% of patients, including 7.8% with serious AEs. The most common afatinib-related AEs (all grades) were diarrhea (77.0%) and rash (36.0%). Dose reductions occurred in 31.1% of patients. Discontinuation rates due to diarrhea (1.6%) or rash/acne (0.3%) were low. Efficacy data were collected and analyzed when available, with 17.1% and 69.9% of patients achieving objective response and disease control, respectively, in this highly pretreated population.
No additional or unexpected safety concerns were revealed, and afatinib demonstrated antitumor activity in a heavily pretreated NSCLC patient population in a routine clinical setting.
ClinicalTrials.gov Identifier: NCT01649284.
Boehringer Ingelheim Pharmaceuticals, Inc.
阿法替尼是一种口服的不可逆表皮生长因子受体（ErbB）家族阻滞剂，被批准用于一线治疗转移性表皮生长因子受体（EGFR）突变阳性非小细胞肺癌（NSCLC）。扩大准入计划（EAP）使患者能够提前获得阿法替尼，并提供了关于其安全性、耐受性和疗效的更多数据。
阿法替尼EAP是美国一项开放标签、多中心、单臂研究，治疗并随访携带EGFR突变的局部晚期或转移性NSCLC患者。口服阿法替尼40mg，每日一次，直至因疾病进展、不良事件（AE）或改用市售药物而停药。
322例患者接受了≥1剂阿法替尼。大多数患者曾接受过先前的治疗。89.4%的患者发生了与药物相关的AE，其中7.8%为严重AE。最常见的与阿法替尼相关的AE（所有级别）为腹泻（77.0%）和皮疹（36.0%）。31.1%的患者出现剂量减少。因腹泻（1.6%）或皮疹/痤疮（0.3%）导致的停药率较低。在可行时收集并分析疗效数据，在这个经过高度预处理的人群中，分别有17.1%和69.9%的患者实现了客观缓解和疾病控制。
未发现额外或意外的安全问题，并且在常规临床环境中，阿法替尼在经过高度预处理的NSCLC患者人群中显示出抗肿瘤活性。
ClinicalTrials.gov标识符：NCT01649284。
勃林格殷格翰制药公司。
