近日，辉瑞公司表示，其每日给药一次的口服制剂Dacomitinib（商品名：VIZIMPRO）已经获得美国食品和药物管理局的批准用于既往未经治疗的患有转移性非小细胞肺癌（NSCLC）的患者。
批准日期：2018年9 月28日 公司：辉瑞公司
VIZIMPRO（达克替尼 dacomitinib）片剂，用于口服
美国最初批准：2018年
作用机制
Dacomitinib是人EGFR家族（EGFR/HER1，HER2和HER4）和某些EGFR激活突变（外显子19缺失或外显子21 L858R取代突变）的激酶活性的不可逆抑制剂。 体外达克替尼还在临床相关浓度下抑制DDR1，EPHA6，LCK，DDR2和MNK1的活性。
达克替尼显示出由HER家族靶标（包括突变的EGFR）驱动的皮下植入的人肿瘤异种移植物的小鼠中EGFR和HER2自身磷酸化和肿瘤生长的剂量依赖性抑制。 Dacomitinib在由EGFR扩增驱动的颅内人肿瘤异种移植物的口服给药小鼠中也显示出抗肿瘤活性。
适应症和用法
VIZIMPRO是一种激酶抑制剂，适用于转移性非小细胞肺癌（NSCLC）患者的一线治疗，表皮生长因子受体（EGFR）外显子19缺失或外显子21 L858R替代突变，经FDA批准的检测。
剂量和给药
推荐剂量：每日口服45毫克，含或不含食物。
剂量形式和强度
片剂：15mg，30mg和45mg。
禁忌症
没有。
警告和注意事项
■间质性肺病（ILD）：如果确诊ILD，则永久停用VIZIMPRO。
■腹泻：根据严重程度扣留并减少VIZIMPRO的剂量。
■皮肤病学不良反应：根据严重程度扣留并减少VIZIMPRO的剂量。
■胚胎-胎儿毒性：VIZIMPRO会导致胎儿伤害。建议具有生殖潜力的女性使用有效的避孕措施。
不良反应
最常见的不良反应是（发病率> 20％）腹泻，皮疹，甲沟炎，口腔炎，食欲减退，皮肤干燥，体重减轻，脱发，咳嗽和瘙痒。
要报告疑似不良反应，请致电1-800-438-1985联系辉瑞公司，或致电1-800-FDA-1088或www.fda.gov/medwatch联系FDA。
药物相互作用
■质子泵抑制剂（PPIs）：避免与VIZIMPRO一起使用;使用局部作用的抗酸剂或H2受体拮抗剂;在H2受体拮抗剂之前至少6小时或10小时后给予VIZIMPRO。
■CYP2D6底物：避免与VIZIMPRO同时使用，其中CYP2D6底物浓度的最小增加可能导致严重或危及生命的毒性。
用于特定人群
■哺乳期：建议不要母乳喂养。
包装提供/存储和处理
VIZIMPRO提供强度和包装配置，如下表6所示：
VIZIMPRO强度和包配置VIZIMPRO平板电脑
包装配置片剂强度（mg）NDC片剂描述
带有防儿童闭合装置的30支装瓶15 0069-0197-30蓝色薄膜涂层，立即释放，圆形双凸面片剂，一面用“Pfizer”压印，另一面用“DCB15”压印。
带有防儿童闭合装置的30支装瓶30 0069-1198-30蓝色薄膜涂层立即释放，圆形双凸面片，一面用“Pfizer”压印，另一面用“DCB30”压印。
带有防儿童闭合装置的30支装瓶45 0069-2299-30蓝色薄膜涂层立即释放，圆形双凸面片，一面用“Pfizer”压印，另一面用“DCB45”压印。
储存在20°C至25°C（68°F至77°F）; 允许的偏差在15°C至30°C（59°F至86°F）之间。 [见USP受控室温]。
完整资料附件：
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/211288s000lbl.pdf
Vizimpro Approved as First-Line Treatment for EGFR-Mutated Metastatic NSCLC
The Food and Drug Administration (FDA) has approved Vizimpro (dacomitinib; Pfizer) for the first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor (EGFR) exon 19 deletion or exon 21 L858R substitution mutations as detected by an FDA-approved test.
The approval was based on data from the ARCHER 1050 open-label, active controlled study which randomized patients with unresectable, metastatic NSCLC to treatment with either dacomitinib (N=227) or gefitinib (N=225). Patients were required to have unresectable, metastatic NSCLC with no prior therapy for metastatic disease or recurrent disease with a minimum of 12 months disease-free after completion of systemic therapy; an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1; EGFR exon 19 deletion or exon 21 L858R substitution mutations. The major efficacy outcome measure was progression-free survival (PFS) as determined by blinded Independent Radiologic Central review.
Results showed treatment with dacomitinib was associated with a statistically significant improvement in PFS compared with gefitinib (hazard ratio 0.59 [95% CI: 0.47, 0.74], P<.0001), however no significant improvements in overall response rate (75% for dacomitinib vs 72% for gefitinib; P=.39) or overall survival were observed. Median PFS in the dacomitinib group was 14.7 months vs 9.2 in the gefitinib arm.
“EGFR-mutated advanced non-small cell lung cancer is a common illness, especially in the Asian population, and new treatment options will ultimately benefit patients,” said Professor Tony Mok, MD, primary investigator for the ARCHER 1050 study and Chair of Department of Clinical Oncology, The Chinese University of Hong Kong. “The findings from ARCHER 1050 suggest that Vizimpro should be considered as a new first-line treatment option for patients with EGFR-mutated non-small cell lung cancer exon 19 deletion or exon 21 L858R substitution mutations.”
With regard to safety, the most common adverse reactions associated with dacomitnib treatment include diarrhea, rash, paronychia, stomatitis, decreased appetite, dry skin, decreased weight, alopecia, cough, and pruritus.
Vizimpro, a kinase inhibitor, will be supplied in 15mg, 30mg, and 45mg tablet strengths.