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Prognostic Impact of Baseline Liver Metastasis in ALK Fusion-Positive Metastatic Lung Cancer: A Retrospective Review

Introduction  The prognosis of anaplastic lymphoma kinase (ALK) fusion-positive metastatic non-small cell lung cancer (mNSCLC) patients has improved drastically since the introduction of targeted therapies. Apart from age, performance status, and type of driver mutation in a mNSCLC, prognosis also d...

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Autores principales: Khaddar, Satvik, Kapoor, Akhil, Noronha, Vanita, Patil, Vijay M., Menon, Nandini, Mahajan, Abhishek, Janu, Amit, Kumar, Rajiv, Purandare, Nilendu, Prabhash, Kumar
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Thieme Medical and Scientific Publishers Pvt. Ltd. 2022
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9803546/
https://www.ncbi.nlm.nih.gov/pubmed/36588605
http://dx.doi.org/10.1055/s-0042-1742596
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author Khaddar, Satvik
Kapoor, Akhil
Noronha, Vanita
Patil, Vijay M.
Menon, Nandini
Mahajan, Abhishek
Janu, Amit
Kumar, Rajiv
Purandare, Nilendu
Prabhash, Kumar
author_facet Khaddar, Satvik
Kapoor, Akhil
Noronha, Vanita
Patil, Vijay M.
Menon, Nandini
Mahajan, Abhishek
Janu, Amit
Kumar, Rajiv
Purandare, Nilendu
Prabhash, Kumar
author_sort Khaddar, Satvik
collection PubMed
description Introduction  The prognosis of anaplastic lymphoma kinase (ALK) fusion-positive metastatic non-small cell lung cancer (mNSCLC) patients has improved drastically since the introduction of targeted therapies. Apart from age, performance status, and type of driver mutation in a mNSCLC, prognosis also depends on baseline metastatic sites number as well as location with liver metastases being a poor prognostic factor. However, the clinical and prognostic association of baseline liver metastases in ALK fusion-positive mNSCLC is not well known. Material and Methods  We performed a retrospective analysis of ALK fusion-positive mNSCLC patients to assess prognostic impact of liver metastases. Records were obtained from lung cancer audit database and electronic medical records. Patients were started on either chemotherapy, ALK-directed tyrosine kinase inhibitors, or given best supportive care as per the clinical scenario. Radiological response was assessed every 2 to 3 months or earlier at clinical suspicion of progressive disease. Adverse events were evaluated as per Common Terminology Criteria for Adverse Events v4.02. Results  A total of 441 patients were screened, out of which 76 had baseline liver metastases. Median age was 49 years with 64.5% males. Median progression-free survival (mPFS) was 14.2 months (95% confidence interval [CI] 8.9–19.4) in patients with baseline liver metastases. In patients who received first-line ALK inhibitor therapy versus who received first-line chemotherapy, mPFS was significantly better in the ALK-directed therapy subgroup, 15.3 months (95% CI 11.7–18.9) versus 5.9 months (95% CI 2.7–9.1), respectively (hazard ratio [HR] 0.3 [95% CI 0.17–0.54]; p  < 0.001). Median overall survival (mOS) was 27.6 months (95% CI 17.4–37.7) in patients with baseline liver metastases which was not statistically significant from patients without baseline liver metastases which was 32.3 months (95% CI 28.8–35.7) (HR 1.32 [95% CI 0.91–1.9]; p  = 0.22). Use of ALK-directed therapy in patients with baseline liver metastases resulted in better OS, mOS not reached versus 15.7 months (95% CI 2.7–28.8) in the chemotherapy group (HR 0.33 [95% CI 0.16—0.67]; p  < 0.001). Conclusion  In patients with ALK fusion-positive mNSCLC, baseline liver metastases was not found to be an independent prognostic factor. However, the use of ALK-directed therapy resulted in a significantly better PFS and OS as compared with chemotherapy in patients with baseline liver metastases. This underscores the importance of the use of ALK-directed therapy whenever feasible in this group of patients.
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spelling pubmed-98035462022-12-31 Prognostic Impact of Baseline Liver Metastasis in ALK Fusion-Positive Metastatic Lung Cancer: A Retrospective Review Khaddar, Satvik Kapoor, Akhil Noronha, Vanita Patil, Vijay M. Menon, Nandini Mahajan, Abhishek Janu, Amit Kumar, Rajiv Purandare, Nilendu Prabhash, Kumar South Asian J Cancer Introduction  The prognosis of anaplastic lymphoma kinase (ALK) fusion-positive metastatic non-small cell lung cancer (mNSCLC) patients has improved drastically since the introduction of targeted therapies. Apart from age, performance status, and type of driver mutation in a mNSCLC, prognosis also depends on baseline metastatic sites number as well as location with liver metastases being a poor prognostic factor. However, the clinical and prognostic association of baseline liver metastases in ALK fusion-positive mNSCLC is not well known. Material and Methods  We performed a retrospective analysis of ALK fusion-positive mNSCLC patients to assess prognostic impact of liver metastases. Records were obtained from lung cancer audit database and electronic medical records. Patients were started on either chemotherapy, ALK-directed tyrosine kinase inhibitors, or given best supportive care as per the clinical scenario. Radiological response was assessed every 2 to 3 months or earlier at clinical suspicion of progressive disease. Adverse events were evaluated as per Common Terminology Criteria for Adverse Events v4.02. Results  A total of 441 patients were screened, out of which 76 had baseline liver metastases. Median age was 49 years with 64.5% males. Median progression-free survival (mPFS) was 14.2 months (95% confidence interval [CI] 8.9–19.4) in patients with baseline liver metastases. In patients who received first-line ALK inhibitor therapy versus who received first-line chemotherapy, mPFS was significantly better in the ALK-directed therapy subgroup, 15.3 months (95% CI 11.7–18.9) versus 5.9 months (95% CI 2.7–9.1), respectively (hazard ratio [HR] 0.3 [95% CI 0.17–0.54]; p  < 0.001). Median overall survival (mOS) was 27.6 months (95% CI 17.4–37.7) in patients with baseline liver metastases which was not statistically significant from patients without baseline liver metastases which was 32.3 months (95% CI 28.8–35.7) (HR 1.32 [95% CI 0.91–1.9]; p  = 0.22). Use of ALK-directed therapy in patients with baseline liver metastases resulted in better OS, mOS not reached versus 15.7 months (95% CI 2.7–28.8) in the chemotherapy group (HR 0.33 [95% CI 0.16—0.67]; p  < 0.001). Conclusion  In patients with ALK fusion-positive mNSCLC, baseline liver metastases was not found to be an independent prognostic factor. However, the use of ALK-directed therapy resulted in a significantly better PFS and OS as compared with chemotherapy in patients with baseline liver metastases. This underscores the importance of the use of ALK-directed therapy whenever feasible in this group of patients. Thieme Medical and Scientific Publishers Pvt. Ltd. 2022-03-22 /pmc/articles/PMC9803546/ /pubmed/36588605 http://dx.doi.org/10.1055/s-0042-1742596 Text en MedIntel Services Pvt Ltd. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ) https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License, which permits unrestricted reproduction and distribution, for non-commercial purposes only; and use and reproduction, but not distribution, of adapted material for non-commercial purposes only, provided the original work is properly cited.
spellingShingle Khaddar, Satvik
Kapoor, Akhil
Noronha, Vanita
Patil, Vijay M.
Menon, Nandini
Mahajan, Abhishek
Janu, Amit
Kumar, Rajiv
Purandare, Nilendu
Prabhash, Kumar
Prognostic Impact of Baseline Liver Metastasis in ALK Fusion-Positive Metastatic Lung Cancer: A Retrospective Review
title Prognostic Impact of Baseline Liver Metastasis in ALK Fusion-Positive Metastatic Lung Cancer: A Retrospective Review
title_full Prognostic Impact of Baseline Liver Metastasis in ALK Fusion-Positive Metastatic Lung Cancer: A Retrospective Review
title_fullStr Prognostic Impact of Baseline Liver Metastasis in ALK Fusion-Positive Metastatic Lung Cancer: A Retrospective Review
title_full_unstemmed Prognostic Impact of Baseline Liver Metastasis in ALK Fusion-Positive Metastatic Lung Cancer: A Retrospective Review
title_short Prognostic Impact of Baseline Liver Metastasis in ALK Fusion-Positive Metastatic Lung Cancer: A Retrospective Review
title_sort prognostic impact of baseline liver metastasis in alk fusion-positive metastatic lung cancer: a retrospective review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9803546/
https://www.ncbi.nlm.nih.gov/pubmed/36588605
http://dx.doi.org/10.1055/s-0042-1742596
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