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

Autor: Patel A; Department of Medical Oncology, Army Hospital Research and Referral, New Delhi, India., Soneji D; Department of Medical Oncology, Army Hospital Research and Referral, New Delhi, India., Singh HP; Department of Medical Oncology, Army Hospital Research and Referral, New Delhi, India., Kumar M; Department of Medical Oncology, Army Hospital Research and Referral, New Delhi, India., Bandyopadhyay A; Department of Surgical Oncology, Command Hospital (Eastern Command), Kolkata, West Bengal, India., Mathur A; Department of Interventional Radiology, Army Hospital Research and Referral, New Delhi, India., Sharma A; Department of Gastrointestinal Surgery, Army Hospital Research and Referral, New Delhi, India., Gahlot GPS; Department of Pathology, Army Hospital Research and Referral, New Delhi, India., Ms S; Department of Medical Oncology, Army Hospital Research and Referral, New Delhi, India., Guleria B; Department of Medical Oncology, Army Hospital Research and Referral, New Delhi, India., Nair R; Department of Medical Oncology, Army Hospital Research and Referral, New Delhi, India., Bhuva D; Department of Medical Oncology, Army Hospital Research and Referral, New Delhi, India., Pandalanghat S; Department of Medical Oncology, Army Hospital Research and Referral, New Delhi, India.
Jazyk: angličtina
Zdroj: South Asian journal of cancer [South Asian J Cancer] 2020 Jun; Vol. 9 (2), pp. 74-79. Date of Electronic Publication: 2020 Dec 14.
DOI: 10.1055/s-0040-1721180
Abstrakt: 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.
Competing Interests: Conflicts of Interest There are no conflicts of interest.
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Databáze: MEDLINE
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