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CC BY-NC-ND 4.0 · South Asian J Cancer 2020; 9(02): 074-079
DOI: 10.1055/s-0040-1721180
Original Article: GI Cancers and Hepatobilliary Malignancies

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

Amol Patel
1   Department of Medical Oncology, Army Hospital Research and Referral, New Delhi, India
,
Dharmesh Soneji
1   Department of Medical Oncology, Army Hospital Research and Referral, New Delhi, India
,
Harinder Pal Singh
1   Department of Medical Oncology, Army Hospital Research and Referral, New Delhi, India
,
Manish Kumar
1   Department of Medical Oncology, Army Hospital Research and Referral, New Delhi, India
,
Arnab Bandyopadhyay
2   Department of Surgical Oncology, Command Hospital (Eastern Command), Kolkata, West Bengal, India
,
Ankit Mathur
3   Department of Interventional Radiology, Army Hospital Research and Referral, New Delhi, India
,
Anuj Sharma
4   Department of Gastrointestinal Surgery, Army Hospital Research and Referral, New Delhi, India
,
Gaurav Prakash Singh Gahlot
5   Department of Pathology, Army Hospital Research and Referral, New Delhi, India
,
Shivashankara MS
1   Department of Medical Oncology, Army Hospital Research and Referral, New Delhi, India
,
Bhupesh Guleria
1   Department of Medical Oncology, Army Hospital Research and Referral, New Delhi, India
,
Rajesh Nair
1   Department of Medical Oncology, Army Hospital Research and Referral, New Delhi, India
,
Dipen Bhuva
1   Department of Medical Oncology, Army Hospital Research and Referral, New Delhi, India
,
Suresh Pandalanghat
1   Department of Medical Oncology, Army Hospital Research and Referral, New Delhi, India
› Author Affiliations Funding FMI (Foundation Medicine, Inc) supported evaluation samples for this study.
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Abstract

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.

Keywords

comprehensive genomic profiling - ERBB2/3 - gallbladder cancer - targeted therapy

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Publication History

Article published online:
14 December 2020

© 2020. 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/)

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