Pooled Analysis of CNS Response to Alectinib in Two Studies of Pretreated Patients With ALK-Positive Non-Small-Cell Lung Cancer
Pooled Analysis of CNS Response to Alectinib in Two Studies of Pretreated Patients With ALK-Positive Non-Small-Cell Lung Cancer
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DOI：
10.1200/jco.2016.68.4639
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发表时间：
2016-12-01
影响因子：
45.3
通讯作者：
Ou, Sai-Hong Ignatius
中科院分区：
文献类型：
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作者：
Gadgeel, Shirish M.;Shaw, Alice T.;Ou, Sai-Hong Ignatius
目的Alectinib在I期和II期研究中显示出对CNS的活性。为了进一步评估该活性，我们汇总了两项单组II期研究（NP 28761和NP 28673; ClinicalTrials.gov标识符：NCT 01871805和NCT 01801111）在ALK阳性非小细胞肺癌（NSCLC）患者中的作用。患者和方法这两项研究均包括ALK阳性NSCLC患者谁曾接受过克唑替尼;所有患者接受阿来替尼600毫克，每天两次。两项研究的主要终点均为独立审查委员会（IRC）评估的客观缓解率（ORR;根据实体瘤疗效评价标准[ RECIST]第1.1版）。额外的终点（所有IRC）包括中枢神经系统的ORR（CORR），中枢神经系统疾病控制率（CDCR），和中枢神经系统的反应持续时间（CDOR）threats 136例患者的基线中枢神经系统转移（60%的总体研究人群），50例（37%）有可测量的中枢神经系统疾病在基线。95例患者（70%）既往接受过CNS放疗; 55例患者在开始alectinib治疗前6个月以上完成了CNS放疗。中位随访时间为12.4个月（范围：0.9 - 19.7个月）。对于基线可测量CNS疾病的患者，IRC CORR为64.0%（95% CI，49.2%-77.1%），CDCR为90.0%（95% CI，78.2%-96.7%），中位CDOR为10.8个月（95% CI，7.6 - 14.1个月）。对于基线CNS疾病可测量和/或不可测量的患者，IRC CORR为42.6%（95% CI，34.2%-51.4%），CDCR为85.3%（95% CI，78.2%-90.8%），中位CDOR为11.1个月（95% CI，10.3个月至不可评价）。既往接受过放疗的患者（n = 95）的CORR为35.8%（95% CI，26.2%至46.3%），既往未接受过放疗的患者（n = 41）的CORR为58.5%（95% CI，42.1%至73.7%）。如前所述，Alectinib耐受性良好，无论基线CNS diseases.ConclusionAlectinib对CNS转移显示出良好的疗效，除了全身活性，在克唑替尼难治性ALK阳性NSCLC。(C)2016年美国临床肿瘤学会
PurposeAlectinib has shown activity in the CNS in phase I and II studies. To further evaluate this activity, we pooled efficacy and safety data from two single-arm phase II studies (NP28761 and NP28673; ClinicalTrials.gov identifiers: NCT01871805 and NCT01801111, respectively) in patients with ALK-positive non-small-cell lung cancer (NSCLC).Patients and MethodsBoth studies included patients with ALK-positive NSCLC who had previously received crizotinib; all patients received alectinib 600 mg twice per day. The primary end point in both studies was independent review committee (IRC)-assessed objective response rate (ORR; by Response Evaluation Criteria in Solid Tumors [ RECIST] version 1.1). Additional end points (all by IRC) included CNS ORR (CORR), CNS disease control rate (CDCR), and CNS duration of response (CDOR).ResultsOne hundred thirty-six patients had baseline CNS metastases (60% of the overall study populations); 50 patients (37%) had measurable CNS disease at baseline. Ninety-five patients (70%) had prior CNS radiotherapy; 55 patients completed the CNS radiotherapy more than 6 months before starting alectinib. Median follow-up time was 12.4 months (range, 0.9 to 19.7 months). For patients with baseline measurable CNS disease, IRC CORR was 64.0% (95% CI, 49.2% to 77.1%), CDCR was 90.0% (95% CI, 78.2% to 96.7%), and median CDOR was 10.8 months (95% CI, 7.6 to 14.1 months). For patients with measurable and/or nonmeasurable baseline CNS disease, IRC CORR was 42.6% (95% CI, 34.2% to 51.4%), CDCR was 85.3% (95% CI, 78.2% to 90.8%), and median CDOR was 11.1 months (95% CI, 10.3 months to not evaluable). CORR was 35.8% (95% CI, 26.2% to 46.3%) for patients with prior radiotherapy (n = 95) and 58.5% (95% CI, 42.1% to 73.7%) for patients without prior radiotherapy (n = 41). As previously reported, alectinib was well tolerated, regardless of baseline CNS disease.ConclusionAlectinib showed good efficacy against CNS metastases, in addition to systemic activity, in crizotinib-refractory ALK-positive NSCLC. (C) 2016 by American Society of Clinical Oncology