Abstract 109P
Background
The therapeutic scenario of metastatic biliary tract cancers (BTCs) beyond first line has recently expanded with the introduction of targeted therapies, owing to a deeper understanding of the mechanisms at the basis of these tumors and the identification of actionable alterations potentially targetable by specific drugs. Data concerning the prognostic impact of target-directed therapies after progression to cisplatin-gemcitabine-durvalumab (CGD) in patients harboring molecular alterations are limited. The present study aims to evaluate the outcomes of patients carrying actionable alterations and treated with targeted therapies according to their molecular alteration in a large worldwide population of advanced/metastatic BTCs who received CGD in first line.
Methods
The study population included 666 patients with unresectable, locally advanced, or metastatic BTCs coming from 11 countries across the world, treated with CGD in the first-line setting from July 2021 to December 2023. Data were retrospectively collected from genomic analysis reports.
Results
Data of genomic testing was available for 513 patients (77.0%). In this population median progression free survival (PFS) was 8.4 months (95% CI: 7.6-9.0), and median overall survival (OS) was 15.9 months (95% CI: 13.9-29.1). 42 patents with actionable alterations were identified, and 24 (57.1%) of them received a targeted therapy beyond first line according to the molecular alteration. More specifically, 8 patients received ivosidenib, 8 anti-HER2 drugs, 7 pemigatinib, and 1 dabrafenib plus trametinib. The remaining 18 patients (42.9%), despite having a molecular alteration, did not receive targeted therapy and were treated with chemotherapy. Patients who received a targeted therapy showed statistically significant better OS compared to patients treated with chemotherapy (NR vs. 4.2 months, HR 0.12; 95% CI 0.04-0.37; p=0.003).
Conclusions
Our study showed a statistically significant improvement in OS in advanced/metastatic BTCs patients carrying a molecular alteration and treated with a target-directed therapy beyond first line, thus highlighting the need to expand access to these treatments in order to improve the prognosis of these patients.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
T. Pressiani: Financial Interests, Personal, Invited Speaker: Bayer, Ipsen, AstraZeneca, Roche. L. Rimassa: Financial Interests, Personal, Invited Speaker: AbbVie, Basilea, Bayer, BMS, Elevar Therapeutics, Genenta, Hengrui, Ipsen, IQVIA, Jazz Pharmaceuticals, MSD, Guerbet; Financial Interests, Personal and Institutional, Invited Speaker: AstraZeneca, Exelixis, Incyte, Nerviano Medical Sciences, Roche, Servier, Taiho Oncology, Zymeworks; Financial Interests, Institutional, Research Grant: Agios, BeiGene, Fibrogen, Lilly, TransThera Sciences, Eisai. A. Casadei-Gardini: Financial Interests, Personal and Institutional, Invited Speaker: AstraZeneca, Eisai; Financial Interests, Personal, Invited Speaker: Bayer, BMS, Incyte, Ipsen, Iqvia, MSD, Roche, Servier. All other authors have declared no conflicts of interest.