Examination of Patients With CCA Treated With Novel Targeted Therapies After Extended Molecular Profiling on Liquid Biopsies

Dr Mahmood presented results from the largest multi-institutional review of efficacy outcomes following targeted agents in patients with cholangiocarcinoma.

Patients with cholangiocarcinoma (CCA) have limited treatment options and often a poor prognosis. Although targeted therapeutics are emerging treatment options, it is currently unclear which major clinicopathological features are associated with treatment response and improved survival while on these targeted agents. At the 2023 ESMO Conference in Madrid, Spain, Umair Mahmood, MD, presented the largest multi-institutional review to date evaluating outcomes following targeted agents in patients with CCA.

Patients with CCA who received ≤6 lines of systemic therapy between January 2010 and April 2023 at University College London Hospitals were included in this analysis. The study evaluated overall survival (OS), progression-free survival (PFS), best overall response (BOR) to therapy, and predictors of clinical benefit. Patient demographic factors, disease characteristics, and survival outcomes were evaluated using the Kaplan-Meier method and Cox proportional-hazards models. BOR was assessed using the RECIST version 1.1 criteria.

Patients with CCA who received ≤6 lines of systemic therapy between January 2010 and April 2023 at University College London Hospitals were included in this analysis.

Of 227 screened patients, 56 eligible patients were identified who received targeted therapy for treatment of CCA. The 2 most common genomic alterations in evaluated patients with CCA (n=53) were alterations in FGFR2 and TP53. The median PFS following first-, second-, and third-line systemic therapies was 8.44 (95% confidence interval [CI], 7.49-12.78), 5.65 (95% CI, 3.71-7.13), and 5.55 (95% CI, 2.79-12.58) months, respectively. Median OS for all patients was 29.01 (95% CI, 24.21-42.91) months. OS, but not PFS, was significantly associated with previous CCA-related surgical history (P=.02). Duration of second-line targeted treatment longer than 3.52 months was associated with improved OS (P<.001). Duration of third-line targeted treatment longer than 4.37 months was associated with improved PFS (P=.01) but not OS (P=.15). Median duration of clinical benefit (complete response, partial response, and stable disease) in the second-line chemotherapy setting was 2.99 (range, 2.66-3.91) months, 4.17 (range, 2.33-8.18) months in targeted therapy (with or without chemotherapy), and 5.60 (range, 2.1-7.35) months in patients treated with futibatinib. In the third-line setting, the median duration of clinical benefit was 5.03 (range, 2.63-5.42) months in the chemotherapy group and 7.03 (range, 2.68-12.29) months in the targeted agent (with or without immunotherapy) cohort. The duration extended to 10.09 (range, 4.71-13.17) months in those receiving futibatinib.

This study demonstrated the efficacy of novel therapeutic agents in patients with CCA. The researchers determined that liquid biopsies can reliably provide information on extended molecular profiling, which can aid patient selection for personalized therapeutics.

Source:

Mahmood U, Faizul EM, Howlet S, et al. Compre-hensive examination of cholangiocarcinoma patients treated with novel targeted therapies after extended molecular profiling on liquid biopsies. Presented at: ESMO Congress 2023, October 20-24, 2023; Madrid, Spain.