BACKGROUND: Patients with anaplastic lymphoma kinase (ALK) rearrangements are particularly prone to development of brain metastases (BMs). Newer anti-ALK treatments have demonstrated far greater intracranial efficacy. Here we performed a meta-analysis with the aim of assessing the efficacy of ALK inhibitors on BMs. METHODS: A search of published trials was conducted in PubMed, The Cochrane Library, Web of Science, and Embase. Data were pooled using the number of events/number of evaluable patients (non-small cell lung cancer patients with BMs) according to fixed or random effect models. Intracranial efficacy was assessed through overall response rate (ORR), disease control rate (DCR), and median progression-free survival (PFS). Subgroup analyses for baseline BMs, previous treatment with ALK inhibitor, study type, and current ALK inhibitor were made. RESULTS: Twenty studies accounting for 2,715 patients were included. The pooled iORR was 48% (95% CI: 32-63%) in fifteen single-arm studies. The overall DCR was 65% (95% CI: 60-69%) from three studies include available data. The iORR was 79% (95% CI: 64-91%), 45% (24-67%), 48% (34-63%), 18% (13-24%) in patients receiving alectinib, ceritinib, brigatinib, and crizotinib, respectively. Five randomized studies assessed the intracranial efficacy of anti-ALK agents versus chemotherapy, the pooled RR for iORR was 3.54 (95% CI: 2.38-5.26), and the pooled HR for iPFS was 0.52 (95% CI: 0.36-0.75; P=0.71) estimated in 2 studies. CONCLUSIONS: Despite the limitation from lack of published clinical data, our results showed that ALK inhibitors are effective at the brain site regardless of previous anti-ALK treatments, systemic therapy with ALK inhibitors should be considered as a preferred approach over for controlling BMs from ALK-positive NSCLC.
BACKGROUND: Patients with anaplastic lymphoma kinase (ALK) rearrangements are particularly prone to development of brain metastases (BMs). Newer anti-ALK treatments have demonstrated far greater intracranial efficacy. Here we performed a meta-analysis with the aim of assessing the efficacy of ALK inhibitors on BMs. METHODS: A search of published trials was conducted in PubMed, The Cochrane Library, Web of Science, and Embase. Data were pooled using the number of events/number of evaluable patients (non-small cell lung cancer patients with BMs) according to fixed or random effect models. Intracranial efficacy was assessed through overall response rate (ORR), disease control rate (DCR), and median progression-free survival (PFS). Subgroup analyses for baseline BMs, previous treatment with ALK inhibitor, study type, and current ALK inhibitor were made. RESULTS: Twenty studies accounting for 2,715 patients were included. The pooled iORR was 48% (95% CI: 32-63%) in fifteen single-arm studies. The overall DCR was 65% (95% CI: 60-69%) from three studies include available data. The iORR was 79% (95% CI: 64-91%), 45% (24-67%), 48% (34-63%), 18% (13-24%) in patients receiving alectinib, ceritinib, brigatinib, and crizotinib, respectively. Five randomized studies assessed the intracranial efficacy of anti-ALK agents versus chemotherapy, the pooled RR for iORR was 3.54 (95% CI: 2.38-5.26), and the pooled HR for iPFS was 0.52 (95% CI: 0.36-0.75; P=0.71) estimated in 2 studies. CONCLUSIONS: Despite the limitation from lack of published clinical data, our results showed that ALK inhibitors are effective at the brain site regardless of previous anti-ALK treatments, systemic therapy with ALK inhibitors should be considered as a preferred approach over for controlling BMs from ALK-positive NSCLC.
Authors: N Joan Abbott; Adjanie A K Patabendige; Diana E M Dolman; Siti R Yusof; David J Begley Journal: Neurobiol Dis Date: 2009-08-05 Impact factor: 5.996
Authors: Alice T Shaw; Beow Y Yeap; Mari Mino-Kenudson; Subba R Digumarthy; Daniel B Costa; Rebecca S Heist; Benjamin Solomon; Hannah Stubbs; Sonal Admane; Ultan McDermott; Jeffrey Settleman; Susumu Kobayashi; Eugene J Mark; Scott J Rodig; Lucian R Chirieac; Eunice L Kwak; Thomas J Lynch; A John Iafrate Journal: J Clin Oncol Date: 2009-08-10 Impact factor: 44.544
Authors: Stephen G Chun; Kevin S Choe; Puneeth Iyengar; John S Yordy; Robert D Timmerman Journal: Cancer Biol Ther Date: 2012-09-17 Impact factor: 4.742
Authors: Alice T Shaw; Dong-Wan Kim; Kazuhiko Nakagawa; Takashi Seto; Lucio Crinó; Myung-Ju Ahn; Tommaso De Pas; Benjamin Besse; Benjamin J Solomon; Fiona Blackhall; Yi-Long Wu; Michael Thomas; Kenneth J O'Byrne; Denis Moro-Sibilot; D Ross Camidge; Tony Mok; Vera Hirsh; Gregory J Riely; Shrividya Iyer; Vanessa Tassell; Anna Polli; Keith D Wilner; Pasi A Jänne Journal: N Engl J Med Date: 2013-06-01 Impact factor: 91.245
Authors: Huamao M Lin; Xiaoyun Pan; Alyssa Biller; Kyla J Covey; Hui Huang; Rebecca Sugarman; Fatima Scipione; Howard West Journal: Lung Cancer Manag Date: 2020-11-20