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非小细胞肺癌的靶向治疗:色瑞替尼

发表者:张品良 人已读

【非小细胞肺癌NCCN指南2017第7版】

Discussion 讨论

Treatment Approaches 治疗手段

Targeted Therapies 靶向治疗山东省肿瘤医院呼吸肿瘤内科张品良

Oral TKIs 口服的酪氨酸激酶抑制剂

Ceritinib 色瑞替尼

Ceritinib is an oral TKI ALK inhibitor that is approved by the FDA for patients with ALK-positive metastatic NSCLC who have progressed on or are intolerant to crizotinib. The approval is based on an expanded phase 1 study (ASCEND-1) showing overall response rates of 56% to ceritinib in patients (92/163) who had previously received crizotinib; the 240,633median duration of response was 8.3 months (6.8–9.7). Common grade 3 to 4 adverse events included increased alanine aminotransferase (73 [30%] patients) and increased aspartate aminotransferase (25 [10%]). Some patients with CNS lesions responded to ceritinib. Based on the study and the FDA approval, the NCCN Panel recommends ceritinib as subsequent therapy for patients with ALK-positive NSCLC who have progressed after crizotinib. Patients who do not tolerate crizotinib may be switched to alectinib or ceritinib (if not previously given), or brigatinib. A phase 2 trial (ASCEND-2) assessed ceritinib in patients who had previously received at least 2 or more treatments, had progressed on crizotinib, and had brain metastases. The overall response rate was 38%; the duration of response was 9.7 months (95% CI, 7.1–11.1 months). The intracranial overall response rate was 45.0% (95% CI, 23.1%–68.5%). 

色瑞替尼是一种口服的TKI ALK抑制剂,已被FDA批准用于克唑替尼进展或不能耐受、ALK阳性的转移性非小细胞肺癌患者。批准是根据一项扩展的1期研究(ASCEND-1)显示,在既往已接受克唑替尼治疗的患者中,色瑞替尼治疗的总有效率为56%(92/163);中位疗效持续时间是8.3个月(6.8-9.7)。常见的3-4级不良事件包括丙氨酸氨基转移酶升高(73例[30%])及天冬氨酸转氨酶升高(25例[10%])。某些具有CNS病变的患者对色瑞替尼应答。基于该研究和FDA的批准,研究小组建议色瑞替尼作为ALK阳性的NSCLC患者在克唑替尼进展后的后续治疗。不耐受克唑替尼的患者可以转换至阿雷替尼或色瑞替尼(如果既往未给予)或布加替尼。一项2期试验(ASCEND-2)评估了色瑞替尼治疗既往曾接受过至少2个或以上治疗、克唑替尼进展并有脑转移的患者。总有效率是38%;疗效持续时间是9.7个月(95%CI,7.1-11.1个月)。颅内病变总有效率为45.0%(95%CI,23.1%-68.5%)。

A recent phase 3 trial assessed ceritinib versus platinum-based chemotherapy as first-line therapy for patients with ALK-positive metastatic NSCLC. The data show that PFS was improved when using ceritinib when compared with platinum-based chemotherapy; the median PFS was 16.6 months (95% CI, 12.6–27.2) for ceritinib and 8.1 months (CI, 5.8–11.1) for chemotherapy (hazard ratio 0.55 [95% CI, 0.42–0.73]; P<.00001). For ceritinib, common adverse events included diarrhea (85% [160/189] of patients), nausea (69% [130/189]), vomiting (66% [125/189), and an increase in alanine aminotransferase (60% [114/189]). For chemotherapy, common adverse events included nausea (55% [97/175 patients], vomiting (36% [63/175]), and anemia (35% [62/175]). For the 2017 update (Version 5), the NCCN Panel recommends (category 1) ceritinib as first-line therapy for patients with ALK-positive metastatic NSCLC based on this phase 3 trial. For the 2017 update (Version 7), panel members voted that alectinib (category 1) is the preferred agent for first-line therapy for patients with metastatic NSCLC who are positive for ALK gene rearrangements (see Alectinib in this Discussion). 

最近一项3期试验评估了色瑞替尼与以铂为基础的化疗作为ALK-阳性转移性非小细胞肺癌患者的一线治疗。数据显示,与以铂为基础的化疗相比,使用色瑞替尼延长无进展生存期;中位无进展生存期色瑞替尼是16.6个月(95%CI,12.6-27.2),化疗是8.1个月(CI,5.8-11.1)(风险比为0.55[95% CI,0.42-0.73];P<0.00001)。色瑞替尼常见的不良反应包括腹泻(85% [160/189])、恶心(69%[130/189])、呕吐(66%[125/189)和丙氨酸氨基转移酶升高(60%[114/189])。化疗常见的不良反应包括恶心(55%[97/175])、呕吐(36%[63/175])和贫血(35%[62/175])。根据该3期试验,2017第5版更新,NCCN小组推荐(1类)色瑞替尼作为ALK阳性转移性非小细胞肺癌患者的一线治疗。2017第7版更新,专家组成员投票决定阿雷替尼是ALK基因重排阳性的转移性非小细胞肺癌患者一线治疗首选药物(1类)(见本讨论中的阿雷替尼)。

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发表于:2017-07-11 08:32

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