122P - Largest examination of cholangiocarcinoma (CCA) patients (pts) treated with novel targeted therapies after extended molecular profiling on liquid biopsies

Background

CCA is associated with poor outcomes with limited treatment options. Targeted therapies have recently gained traction in CCA but data remains sparse in this domain. Here, we present the largest multi-institutional review to date evaluating outcomes following targeted agents in this pt population.

Methods

All consecutive CCA pts receiving systemic therapy between 2010 - 2022 at UCLH were included. Treatment response, survival outcomes and predictors of clinical benefit were evaluated. Pt demographic factors, disease characteristics and survival outcomes were evaluated using the Kaplan-Meier method and Cox proportional-hazards models.

Results

Of the 147 screened pts, 119 (81%) underwent molecular profiling. We identified 48 (40%) eligible CCA pts where 47 received molecularly guided targeted treatment. Most pts received targeted agents in a 2^nd treatment line setting (N = 26). Frequently observed genomic alterations occurred in FGFR (N = 21), BRCA (N = 8), KRAS (N = 7), IDH (N = 5) and PIK3 (N = 3) genes. The median progression-free survival (PFS) following 1^st, 2^nd and 3^rd line systemic therapy and overall survival (OS) were: 8.38 (5.45 - 13.50), 5.52 (3.22 - 7.85), 8.15 (2.79 - not reached) and 27.07 (24.21 - 36.63) months, respectively. Median duration of clinical benefit (DoCB) (complete response, partial response and stable disease) in 2^nd line treatment setting was 3.10 (2.31 - 4.20) and 5.32 (2.89 - 8.41) months in the chemotherapy and targeted agent (with or without chemotherapy) cohorts, respectively. In a 3^rd line setting, the median DoCB was 5.03 (2.63 - 5.42) and 8.34 (2.87 - 14.09) months in the chemotherapy and targeted agent (with or without immunotherapy) cohorts, respectively. This duration extended to 9.66 (3.06 - 14.06) months among futibatinib recipients. Duration of 2^nd line targeted treatment was associated with PFS (P < 0.0001) and OS (P < 0.0001). Duration of 3^rd line targeted treatment was associated with PFS (P = 0.001) but not OS (P = 0.14).

Conclusions

Our study demonstrated the efficacy of novel therapeutic agents in CCA. Liquid biopsies can reliably provide information on extended molecular profiling to aid pt selection for personalised therapeutics.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Dr. Khurum Khan.

Funding

Has not received any funding.

Disclosure

D. Hochhauser: Financial Interests, Personal, Stocks/Shares: Roche, Novartis; Financial Interests, Personal, Speaker’s Bureau: Pierre Fabre; Financial Interests, Personal, Funding: Merck Serono; Financial Interests, Personal, Other: Celgene. K. Shiu: Financial Interests, Personal, Invited Speaker, Educational Webinars on CRC and UGI cancer management with immunotherapy: BMS; Financial Interests, Personal, Advisory Board, Advisory Board on Regorafenib for chemorefractory mCRC in readiness for NICE application: Bayer; Financial Interests, Personal, Invited Speaker, Educational webinars on Pembrolizumab for MSI-High CRC, as well as OG cancers: MSD; Financial Interests, Personal, Advisory Board, For Pembrolizumab in CRC of OG cancers pre or NICE application or post NICE approval: MSD; Financial Interests, Personal, Invited Speaker, Webinars on updates on management of mCRC: Merck Serono; Financial Interests, Personal, Advisory Board, On Mirati GI Global Advisory Board: Mirati Therapeutics; Financial Interests, Personal, Invited Speaker, To update company on indications/updates in landscape of immunotherapy and vaccines in GI cancers: Nouscom; Financial Interests, Personal, Advisory Board, Advisory on Cancer of Unknown Primary, new indications of molecular profiling usingFoundation Medicine 1: Roche; Financial Interests, Personal, Advisory Board, Advisory Board on Lonsurf for chemorefractory mCRC in readiness for NICE application: Servier; Financial Interests, Institutional, Local PI, For MATTERHORN Trial: AstraZeneca; Financial Interests, Institutional, Coordinating PI, UK Chief Investigator on KEYNOTE 177, KEYNOTE 859, KEYNOTE 811, LEAP 17, MK1308A-008 trials: MSD; Financial Interests, Institutional, Research Grant, Chief Investigator of investigator initiated, MSD funded NEOPRISM-CRC trial: MSD; Financial Interests, Institutional, Local PI, UCLH PI for LEAP 15 and MK4280A-007 trials: MSD; Financial Interests, Institutional, Coordinating PI, UK Chief Investigator for NOUS209-001 trial: Nouscom; Financial Interests, Institutional, Coordinating PI, UK Chief Investigator for CUPSICO trial: Roche; Financial Interests, Personal, Steering Committee Member, Steering Committee Member of CUPISCO trial: Roche; Non-Financial Interests, Member: ASCO, Association of Cancer Physicians UK. J.A. Bridgewater: Financial Interests, Personal, Advisory Board: Taiho, BMS, Incyte, Basilea, Servier; Financial Interests, Institutional, Funding: Incyte. K.H. Khan: Other, Institutional, Advisory Role: Bayer Health; Other, Institutional, Other: Servier. All other authors have declared no conflicts of interest.