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

 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 , , , , , and . This study evaluates the role of CGP and targeted therapies.  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 amplification received trastuzumab with capecitabine or nab-paclitaxel, and patients with amplification were treated with crizotinib. For mutations, lapatinib plus capecitabine regimen was used.  Fifty patients were studied with a median age of 56 years (range 26-83) and a male-to-female ratio of 1:1.6. and 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 mutations showed response to lapatinib-capecitabine. One patient with amplification responded to crizotinib for 4 weeks. mutations were present in 14% of cases and were independent of aberrations.  GBC is enriched in 28% of patients with and amplifications and/or mutations. Responses are seen with lapatinib in concurrent mutation and amplification. mutation showed response to lapatinib. and are new findings in GBC, which may be targeted.