Efficacy of ALK inhibitors on NSCLC brain metastases: A systematic review and pooled analysis of 21 studies

Fausto Petrelli, C Lazzari, R Ardito, K Borgonovo, A Bulotta, B Conti, M Cabiddu, JF Capitanio, M Brighenti, M. Ghilardi, L Gianni, S Barni, V Gregorc

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Abstract

Background Patients with anaplastic lymphoma kinase rearranged (ALK+) non-small cell lung cancer (NSCLC) have a higher risk of developing brain metastases (BMs) than patients with other NSCLC sub-types. ALK inhibitors have activity in BMs due to ALK+ NSCLC. We performed a systematic review of the literature with the aim of assessing the efficacy of ALK inhibitors on BMs. Material and methods A systematic search of the literature was performed using the databases Pubmed, EMBASE, Web of Science, The Cochrane Library, and SCOPUS. Relevant publications reporting activity of ALK inhibitors in NSCLC BMs were retrieved. Data were pooled using the number of events/number of evaluable patients according to fixed or random effect models. Intracranial tumour response was assessed through overall response rate (ORR), disease control rate (DCR: ORR + stable disease rate), median progression-free survival (PFS), and overall survival (OS). The primary endpoint was intracranial overall response rate (IC ORR). Results A total of 1,016 patients with BMs from 21 studies were analysed. In patients receiving ALK inhibitors in the first line setting, the pooled IC ORR was 39.17% (95%CI 13.1–65.2%), while the pooled IC ORR observed in further lines was 44.2% (95%CI 33.3–55.1%). Intracranial disease control rate (IC DCR) was 70.3% and 78.2% in naïve and pre-treated patients, respectively. Patients who had not received brain radiation attained an IC ORR of 49.0%. Conclusions Based on these data, ALK inhibitors are effective in both naive and pre-treated patients with similar IC ORR and IC DCR, irrespective of the line of therapy. © 2018 Petrelli et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Original languageEnglish
Article numbere0201425
JournalPLoS One
Volume13
Issue number7
DOIs
Publication statusPublished - 2018

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systematic review
lung neoplasms
Non-Small Cell Lung Carcinoma
Brain Neoplasms
metastasis
Brain
Disease control
Neoplasm Metastasis
brain
cells
disease control
Tumors
Licensure
lymphoma
endpoints
Cells
PubMed
Libraries
Disease-Free Survival
Reproduction

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Efficacy of ALK inhibitors on NSCLC brain metastases: A systematic review and pooled analysis of 21 studies. / Petrelli, Fausto; Lazzari, C; Ardito, R; Borgonovo, K; Bulotta, A; Conti, B; Cabiddu, M; Capitanio, JF; Brighenti, M; Ghilardi, M.; Gianni, L; Barni, S; Gregorc, V.

In: PLoS One, Vol. 13, No. 7, e0201425, 2018.

Research output: Contribution to journalArticle

Petrelli, F, Lazzari, C, Ardito, R, Borgonovo, K, Bulotta, A, Conti, B, Cabiddu, M, Capitanio, JF, Brighenti, M, Ghilardi, M, Gianni, L, Barni, S & Gregorc, V 2018, 'Efficacy of ALK inhibitors on NSCLC brain metastases: A systematic review and pooled analysis of 21 studies', PLoS One, vol. 13, no. 7, e0201425. https://doi.org/10.1371/journal.pone.0201425
Petrelli, Fausto ; Lazzari, C ; Ardito, R ; Borgonovo, K ; Bulotta, A ; Conti, B ; Cabiddu, M ; Capitanio, JF ; Brighenti, M ; Ghilardi, M. ; Gianni, L ; Barni, S ; Gregorc, V. / Efficacy of ALK inhibitors on NSCLC brain metastases: A systematic review and pooled analysis of 21 studies. In: PLoS One. 2018 ; Vol. 13, No. 7.
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title = "Efficacy of ALK inhibitors on NSCLC brain metastases: A systematic review and pooled analysis of 21 studies",
abstract = "Background Patients with anaplastic lymphoma kinase rearranged (ALK+) non-small cell lung cancer (NSCLC) have a higher risk of developing brain metastases (BMs) than patients with other NSCLC sub-types. ALK inhibitors have activity in BMs due to ALK+ NSCLC. We performed a systematic review of the literature with the aim of assessing the efficacy of ALK inhibitors on BMs. Material and methods A systematic search of the literature was performed using the databases Pubmed, EMBASE, Web of Science, The Cochrane Library, and SCOPUS. Relevant publications reporting activity of ALK inhibitors in NSCLC BMs were retrieved. Data were pooled using the number of events/number of evaluable patients according to fixed or random effect models. Intracranial tumour response was assessed through overall response rate (ORR), disease control rate (DCR: ORR + stable disease rate), median progression-free survival (PFS), and overall survival (OS). The primary endpoint was intracranial overall response rate (IC ORR). Results A total of 1,016 patients with BMs from 21 studies were analysed. In patients receiving ALK inhibitors in the first line setting, the pooled IC ORR was 39.17{\%} (95{\%}CI 13.1–65.2{\%}), while the pooled IC ORR observed in further lines was 44.2{\%} (95{\%}CI 33.3–55.1{\%}). Intracranial disease control rate (IC DCR) was 70.3{\%} and 78.2{\%} in na{\"i}ve and pre-treated patients, respectively. Patients who had not received brain radiation attained an IC ORR of 49.0{\%}. Conclusions Based on these data, ALK inhibitors are effective in both naive and pre-treated patients with similar IC ORR and IC DCR, irrespective of the line of therapy. {\circledC} 2018 Petrelli et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.",
author = "Fausto Petrelli and C Lazzari and R Ardito and K Borgonovo and A Bulotta and B Conti and M Cabiddu and JF Capitanio and M Brighenti and M. Ghilardi and L Gianni and S Barni and V Gregorc",
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T1 - Efficacy of ALK inhibitors on NSCLC brain metastases: A systematic review and pooled analysis of 21 studies

AU - Petrelli, Fausto

AU - Lazzari, C

AU - Ardito, R

AU - Borgonovo, K

AU - Bulotta, A

AU - Conti, B

AU - Cabiddu, M

AU - Capitanio, JF

AU - Brighenti, M

AU - Ghilardi, M.

AU - Gianni, L

AU - Barni, S

AU - Gregorc, V

PY - 2018

Y1 - 2018

N2 - Background Patients with anaplastic lymphoma kinase rearranged (ALK+) non-small cell lung cancer (NSCLC) have a higher risk of developing brain metastases (BMs) than patients with other NSCLC sub-types. ALK inhibitors have activity in BMs due to ALK+ NSCLC. We performed a systematic review of the literature with the aim of assessing the efficacy of ALK inhibitors on BMs. Material and methods A systematic search of the literature was performed using the databases Pubmed, EMBASE, Web of Science, The Cochrane Library, and SCOPUS. Relevant publications reporting activity of ALK inhibitors in NSCLC BMs were retrieved. Data were pooled using the number of events/number of evaluable patients according to fixed or random effect models. Intracranial tumour response was assessed through overall response rate (ORR), disease control rate (DCR: ORR + stable disease rate), median progression-free survival (PFS), and overall survival (OS). The primary endpoint was intracranial overall response rate (IC ORR). Results A total of 1,016 patients with BMs from 21 studies were analysed. In patients receiving ALK inhibitors in the first line setting, the pooled IC ORR was 39.17% (95%CI 13.1–65.2%), while the pooled IC ORR observed in further lines was 44.2% (95%CI 33.3–55.1%). Intracranial disease control rate (IC DCR) was 70.3% and 78.2% in naïve and pre-treated patients, respectively. Patients who had not received brain radiation attained an IC ORR of 49.0%. Conclusions Based on these data, ALK inhibitors are effective in both naive and pre-treated patients with similar IC ORR and IC DCR, irrespective of the line of therapy. © 2018 Petrelli et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

AB - Background Patients with anaplastic lymphoma kinase rearranged (ALK+) non-small cell lung cancer (NSCLC) have a higher risk of developing brain metastases (BMs) than patients with other NSCLC sub-types. ALK inhibitors have activity in BMs due to ALK+ NSCLC. We performed a systematic review of the literature with the aim of assessing the efficacy of ALK inhibitors on BMs. Material and methods A systematic search of the literature was performed using the databases Pubmed, EMBASE, Web of Science, The Cochrane Library, and SCOPUS. Relevant publications reporting activity of ALK inhibitors in NSCLC BMs were retrieved. Data were pooled using the number of events/number of evaluable patients according to fixed or random effect models. Intracranial tumour response was assessed through overall response rate (ORR), disease control rate (DCR: ORR + stable disease rate), median progression-free survival (PFS), and overall survival (OS). The primary endpoint was intracranial overall response rate (IC ORR). Results A total of 1,016 patients with BMs from 21 studies were analysed. In patients receiving ALK inhibitors in the first line setting, the pooled IC ORR was 39.17% (95%CI 13.1–65.2%), while the pooled IC ORR observed in further lines was 44.2% (95%CI 33.3–55.1%). Intracranial disease control rate (IC DCR) was 70.3% and 78.2% in naïve and pre-treated patients, respectively. Patients who had not received brain radiation attained an IC ORR of 49.0%. Conclusions Based on these data, ALK inhibitors are effective in both naive and pre-treated patients with similar IC ORR and IC DCR, irrespective of the line of therapy. © 2018 Petrelli et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

U2 - 10.1371/journal.pone.0201425

DO - 10.1371/journal.pone.0201425

M3 - Article

VL - 13

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 7

M1 - e0201425

ER -