Role Of Precision Medicine For Patients With Advanced Biliary Tract Cancers

552 Background: Biliary tract cancers (BTC) are rare and heterogeneous cancers with poor prognosis. Several actionable genomic targets have been described in BTC but data on the efficacy of targeted therapies remain limited. The main objectives of this retrospective study was to evaluate the frequency of actionable genomic alterations among BTC and the impact of targeted therapy. Methods: We performed a retrospective analysis on BTC patients seen at Gustave Roussy (IGR) from Dec 2011 to Jul 2019. All clinical and genomic reports were reviewed. Results: The study population included 212 patients with the main following characteristics: median age 61 years, female 51%, intrahepatic cholangiocarcinoma 57%, median of 2 previous lines. Of 212 BTC patients, 170 patients had a genomic profile based on archival tissue or a new tumor biopsy (IGR panel n = 120; Foundation One panel n = 92 ). 124 patients (73%) had at least one genomic alteration and 68 (40%) patients had genomic alteration considered as actionable. The most common actionable targets were FGFR2 rearrangement/mutation (n = 24, 35.3%), HER2/3 mutations (n = 9, 13.2%) and IDH1/2 mutations (n = 7, 10.3%). Of those 68 patients, 58 received the matched targeted therapy: FGFR inhibitor n = 24, HER2/3 inhibitors n = 9, Akt/PIK3CA/mTOR inhibitors n = 7, IDH1 inhibitor n = 6. In the treated population, the objective response rate was 36.2% and the disease control rate 85.1%. Progression-free survival (PFS) was 6.2 months compared to 2.8 months (p = 0.02) for patients who did not received targeted treatment. Overall survival (OS) was 17.7 months compared to 11.0 months (p = 0.03) for patients who did not received targeted treatment. Conclusions: Actionable genomic targets are frequent among BTC. Profiling-directed therapies resulted in a 36% response rate, a 85% tumor control rate and a 6.2 months PFS which compare favorably to second-line chemotherapy. A randomized trial is required to confirm the benefit of precision medicine in BTC.