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Genomic Landscape and Targeted Treatment of Gallbladder Cancer: Results of a First Ongoing Prospective Study

Background  Prognosis of gallbladder cancer (GBC) has not changed in the past 20 years. Comprehensive genomic profiling (CGP) carries potential to determine the actionability for multiple targets, including ERBB2 , ERBB3 , MET , ROSI , FGFR , and PIK3 . This study evaluates the role of CGP and targe...

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Autores principales: Patel, Amol, Soneji, Dharmesh, Singh, Harinder Pal, Kumar, Manish, Bandyopadhyay, Arnab, Mathur, Ankit, Sharma, Anuj, Gahlot, Gaurav Prakash Singh, MS, Shivashankara, Guleria, Bhupesh, Nair, Rajesh, Bhuva, Dipen, Pandalanghat, Suresh
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Thieme Medical and Scientific Publishers Pvt. Ltd 2020
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7745744/
https://www.ncbi.nlm.nih.gov/pubmed/33354548
http://dx.doi.org/10.1055/s-0040-1721180
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author Patel, Amol
Soneji, Dharmesh
Singh, Harinder Pal
Kumar, Manish
Bandyopadhyay, Arnab
Mathur, Ankit
Sharma, Anuj
Gahlot, Gaurav Prakash Singh
MS, Shivashankara
Guleria, Bhupesh
Nair, Rajesh
Bhuva, Dipen
Pandalanghat, Suresh
author_facet Patel, Amol
Soneji, Dharmesh
Singh, Harinder Pal
Kumar, Manish
Bandyopadhyay, Arnab
Mathur, Ankit
Sharma, Anuj
Gahlot, Gaurav Prakash Singh
MS, Shivashankara
Guleria, Bhupesh
Nair, Rajesh
Bhuva, Dipen
Pandalanghat, Suresh
author_sort Patel, Amol
collection PubMed
description Background  Prognosis of gallbladder cancer (GBC) has not changed in the past 20 years. Comprehensive genomic profiling (CGP) carries potential to determine the actionability for multiple targets, including ERBB2 , ERBB3 , MET , ROSI , FGFR , and PIK3 . This study evaluates the role of CGP and targeted therapies. Methods  This is a multicenter, prospective, single-arm study. All consecutive patients of unresectable and/or metastatic GBC of age ≥18 years were enrolled. Hybrid capture-based CGP was performed by Foundation Medicine CDx. All patients received first-line chemotherapy with gemcitabine–cisplatin regimen. Patients with ERBB2/3 amplification received trastuzumab with capecitabine or nab-paclitaxel, and patients with MET amplification were treated with crizotinib. For ERBB2/3 mutations, lapatinib plus capecitabine regimen was used. Results  Fifty patients were studied with a median age of 56 years (range 26–83) and a male-to-female ratio of 1:1.6. ERBB2 and ERBB3 amplification was seen in 9 (18%) and 2 (4%) patients, respectively. Four patients with ERBB2 amplification received trastuzumab and/or lapatinib, showed partial response, and maintained response beyond 12 weeks. One patient had mixed response, whereas two patients progressed on trastuzumab and lapatinib. Three patients with ERBB3 mutations showed response to lapatinib–capecitabine. One patient with MET amplification responded to crizotinib for 4 weeks. PIK3 mutations were present in 14% of cases and were independent of ERBB aberrations. Conclusion  GBC is enriched in 28% of patients with ERBB2 and ERBB3 amplifications and/or mutations. Responses are seen with lapatinib in concurrent ERBB2 mutation and amplification. ERBB3 mutation showed response to lapatinib. MET and PIK3 are new findings in GBC, which may be targeted.
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spelling pubmed-77457442020-12-21 Genomic Landscape and Targeted Treatment of Gallbladder Cancer: Results of a First Ongoing Prospective Study Patel, Amol Soneji, Dharmesh Singh, Harinder Pal Kumar, Manish Bandyopadhyay, Arnab Mathur, Ankit Sharma, Anuj Gahlot, Gaurav Prakash Singh MS, Shivashankara Guleria, Bhupesh Nair, Rajesh Bhuva, Dipen Pandalanghat, Suresh South Asian J Cancer Background  Prognosis of gallbladder cancer (GBC) has not changed in the past 20 years. Comprehensive genomic profiling (CGP) carries potential to determine the actionability for multiple targets, including ERBB2 , ERBB3 , MET , ROSI , FGFR , and PIK3 . This study evaluates the role of CGP and targeted therapies. Methods  This is a multicenter, prospective, single-arm study. All consecutive patients of unresectable and/or metastatic GBC of age ≥18 years were enrolled. Hybrid capture-based CGP was performed by Foundation Medicine CDx. All patients received first-line chemotherapy with gemcitabine–cisplatin regimen. Patients with ERBB2/3 amplification received trastuzumab with capecitabine or nab-paclitaxel, and patients with MET amplification were treated with crizotinib. For ERBB2/3 mutations, lapatinib plus capecitabine regimen was used. Results  Fifty patients were studied with a median age of 56 years (range 26–83) and a male-to-female ratio of 1:1.6. ERBB2 and ERBB3 amplification was seen in 9 (18%) and 2 (4%) patients, respectively. Four patients with ERBB2 amplification received trastuzumab and/or lapatinib, showed partial response, and maintained response beyond 12 weeks. One patient had mixed response, whereas two patients progressed on trastuzumab and lapatinib. Three patients with ERBB3 mutations showed response to lapatinib–capecitabine. One patient with MET amplification responded to crizotinib for 4 weeks. PIK3 mutations were present in 14% of cases and were independent of ERBB aberrations. Conclusion  GBC is enriched in 28% of patients with ERBB2 and ERBB3 amplifications and/or mutations. Responses are seen with lapatinib in concurrent ERBB2 mutation and amplification. ERBB3 mutation showed response to lapatinib. MET and PIK3 are new findings in GBC, which may be targeted. Thieme Medical and Scientific Publishers Pvt. Ltd 2020-06 2020-12-14 /pmc/articles/PMC7745744/ /pubmed/33354548 http://dx.doi.org/10.1055/s-0040-1721180 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 Patel, Amol
Soneji, Dharmesh
Singh, Harinder Pal
Kumar, Manish
Bandyopadhyay, Arnab
Mathur, Ankit
Sharma, Anuj
Gahlot, Gaurav Prakash Singh
MS, Shivashankara
Guleria, Bhupesh
Nair, Rajesh
Bhuva, Dipen
Pandalanghat, Suresh
Genomic Landscape and Targeted Treatment of Gallbladder Cancer: Results of a First Ongoing Prospective Study
title Genomic Landscape and Targeted Treatment of Gallbladder Cancer: Results of a First Ongoing Prospective Study
title_full Genomic Landscape and Targeted Treatment of Gallbladder Cancer: Results of a First Ongoing Prospective Study
title_fullStr Genomic Landscape and Targeted Treatment of Gallbladder Cancer: Results of a First Ongoing Prospective Study
title_full_unstemmed Genomic Landscape and Targeted Treatment of Gallbladder Cancer: Results of a First Ongoing Prospective Study
title_short Genomic Landscape and Targeted Treatment of Gallbladder Cancer: Results of a First Ongoing Prospective Study
title_sort genomic landscape and targeted treatment of gallbladder cancer: results of a first ongoing prospective study
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7745744/
https://www.ncbi.nlm.nih.gov/pubmed/33354548
http://dx.doi.org/10.1055/s-0040-1721180
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