Royal Marsden Hospital and The Institute of Cancer Research, London, UK.
Section of Oncology, Drammen Hospital, Vestre Viken Hospital Trust, PO Box 800, N-3004, Drammen, Norway.
Lung Cancer. 2021 Jul;157:9-16. doi: 10.1016/j.lungcan.2021.05.017. Epub 2021 May 24.
The next-generation ALK inhibitor brigatinib is approved for use in patients with ALK inhibitor-naïve ALK-positive advanced NSCLC and in patients previously treated with crizotinib. A phase II trial showed that brigatinib is active in patients with ALK-positive metastatic NSCLC (mNSCLC) who had progressed on prior crizotinib (response rate 56 %, median PFS 16.7 months, median OS 34.1 months). We report final data from the UVEA-Brig study of brigatinib in ALK inhibitor-pretreated ALK-positive mNSCLC in clinical practice.
UVEA-Brig was a retrospective chart review of patients treated with brigatinib in Italy, Norway, Spain and the UK in an expanded access program. Adults with ALK-positive mNSCLC, including those with brain lesions, resistant to or intolerant of ≥1 prior ALK inhibitor and ECOG performance status ≤3 were eligible. Patients received brigatinib 180 mg once daily with a 7-day lead-in at 90 mg. The objectives were to describe patient characteristics, clinical disease presentation, treatment regimens used and clinical outcomes.
Data for 104 patients (male: 43 %; median age: 53 [29-80] years; ECOG performance status 0/1/2/3: 41/41/10/5 %; brain/CNS metastases: 63 %) were analyzed. Patients had received a median of 2 (1-6) lines of systemic therapy prior to brigatinib (37.5 % received ≥3) and a median of 1 (1-5) lines of prior ALK inhibitor-containing therapy (crizotinib 83.6 %; ceritinib 50.0 %; alectinib 6.7 %; lorlatinib 4.8 %). At the time of analysis, 77 patients had discontinued brigatinib. Overall, the response rate was 39.8 %, median PFS was 11.3 (95 % CI:8.6-12.9) months and median OS was 23.3 (95 % CI: 16.0-NR) months. Four patients discontinued brigatinib treatment due to adverse events. 53 patients received systemic therapy after brigatinib, 42 with an ALK inhibitor (lorlatinib, n = 34).
These real-world data indicate the activity and tolerability of brigatinib in patients with ALK-positive mNSCLC who were more heavily pretreated than patients included in clinical trials.
下一代 ALK 抑制剂布加替尼适用于 ALK 抑制剂初治的 ALK 阳性晚期 NSCLC 患者，以及先前接受过克唑替尼治疗的患者。一项 II 期临床试验表明，布加替尼对先前接受过克唑替尼治疗后进展的 ALK 阳性转移性 NSCLC（mNSCLC）患者具有活性（缓解率为 56%，中位无进展生存期 16.7 个月，中位总生存期 34.1 个月）。我们报告了在临床实践中，ALK 抑制剂预处理的 ALK 阳性 mNSCLC 患者接受布加替尼治疗的 UVEA-Brig 研究的最终数据。
UVEA-Brig 是一项回顾性图表审查，评估了意大利、挪威、西班牙和英国接受扩展准入计划中布加替尼治疗的患者。ALK 阳性 mNSCLC 患者，包括有脑转移的患者，对至少 1 种既往 ALK 抑制剂耐药或不耐受，ECOG 体能状态评分 ≤3，符合条件。患者接受布加替尼 180mg 每日一次，7 天导入期剂量为 90mg。研究目的是描述患者特征、临床表现、治疗方案和临床结局。
共分析了 104 例患者的数据（男性：43%；中位年龄：53[29-80]岁；ECOG 体能状态 0/1/2/3：41/41/10/5%；脑/CNS 转移：63%）。患者在接受布加替尼治疗前接受了中位数为 2（1-6）线的系统治疗（37.5%接受了≥3 线治疗），并接受了中位数为 1（1-5）线的既往含 ALK 抑制剂的治疗（克唑替尼 83.6%；塞瑞替尼 50.0%；阿来替尼 6.7%；劳拉替尼 4.8%）。在分析时，77 例患者已停止布加替尼治疗。总体而言，缓解率为 39.8%，中位无进展生存期为 11.3（95%CI：8.6-12.9）个月，中位总生存期为 23.3（95%CI：16.0-NR）个月。有 4 例患者因不良事件停止布加替尼治疗。53 例患者在接受布加替尼治疗后接受了系统治疗，其中 42 例接受了 ALK 抑制剂（劳拉替尼，n=34）。
这些真实世界的数据表明，在 ALK 阳性 mNSCLC 患者中，布加替尼的活性和耐受性优于临床试验中的患者，这些患者接受了更多的预处理。
