Utility of Liquid Biopsy for Identification of Molecular Alterations in Solid Tumors

2022 Year in Review: Cholangiocarcinoma — January 4, 2023

Identifying molecular alterations in patients with cancer is an important component of personalized therapy, which is supported by a growing body of evidence. Liquid biopsy, or cell-free DNA analysis, is a novel, noninvasive approach for identifying molecular alterations that has been confirmed in clinical trials, but real-world evidence has not yet been examined. This prospective, real-world study sought to examine liquid biopsy in international patients with cancer, specifically with the intent to offer personalized therapies. Results were shared at the 2022 ESMO congress.

A total of 47 patients were admitted to the international department of Gustave Roussy with advanced solid cancers, and cell-free DNA was extracted from the patients’ peripheral blood and sent for sequencing.

The median age of the patients was 60.5 years, and 53% of the patients were men. The primary site of cancer for these patients varied and included digestive (n = 20; 41%), lung (n = 9; 19%), sarcomas (n = 6; 13%), breast (n = 5; 11%), and other (n = 7; 16%). Treatment history also varied: 17 patients (36.2%) were treatment-naïve, 34 (73.3%) were previously treated with chemotherapy, and 16 (34%) were previously treated with immunotherapy. On the day of liquid biopsy, 43 patients (91.5%) had distant metastases. Patients with ECOG performance status scores 0-1 and ≥2 were split evenly with 24 patients (50%) in each group. The median number of previous lines of therapy was 1.

Only 2 patients had insufficient cell-free DNA to complete the liquid biopsy. For the remaining patients, the median number of molecular alterations was 5. In 7 patients, the tumor mutational burden was ≥10, suggesting that immunotherapy may be a treatment option. In addition, 10 molecular alterations with available options for treatment were identified in 9 patients: KRAS G12C (1 lung, 1 pancreatic), EGFR (1 lung), IDH1 (1 cholangiocarcinoma), BRAF (1 angiosarcoma, 1 colon), BRCA2 (1 pancreatic), PIK3CA (2 breast), and FGFR3 (1 bladder). Oncoprint genes were altered in ≥5% of patients.

The identification of the molecular alterations allowed for 15 patients (31.9%) to be offered an innovative approach to treatment. In addition, 16 patients (with 22 molecular alterations among them) were identified as potential participants in phase 1 or 2 clinical trials.

This study supports the role of liquid biopsy as a tool to identify molecular alterations with diagnostic and therapeutic implications.

Sources: Assi TS, Ibrahim T, Chahine C, et al. Liquid biopsy, a tool to detect genetic alterations with therapeutic impact in international patients: prospective data on 47 patients from Gustave Roussy. Ann Oncol. 2022;33(suppl 7):S580.

Assi TS, Ibrahim T, Chahine C, et al. Liquid biopsy, a tool to detect genetic alterations with therapeutic impact in international patients: prospective data on 47 patients from Gustave Roussy. European Society for Medical Oncology Congress 2022. Abstract 91P.

Related Items

Evolving Targeted Treatment Landscape in Biliary Tract Cancer
Web Exclusives
The podcast provides peer-to-peer physician perspectives on targeted treatments in BTC, focusing on fibroblast growth factor receptor (FGFR) inhibitors.
First-Line Treatment of Advanced Biliary Tract Cancers (BTCs)
Ask the Expert
Use of first-line (1L) IMFINZI® (durvalumab) in combination with gemcitabine and cisplatin (gem-cis) chemotherapy in patients with locally advanced or metastatic biliary tract cancers
KEYNOTE-966: Pembrolizumab Combined With GemCis Versus GemCis Alone in Patients With BTC
2023 Year in Review: Cholangiocarcinoma
In the KEYNOTE-966 study, pembrolizumab was added to gemcitabine/cisplatin to assess outcomes in patients with advanced biliary tract cancer.
Post-hoc Analysis of the ABC-01, -02, and -03 Trials in Patients With Advanced eCCA
2023 Year in Review: Cholangiocarcinoma
This post-hoc analysis of the ABC-01, -02, and -03 clinical trials provides reference survival data for patients with advanced extrahepatic cholangiocarcinoma treated with first-line gemcitabine/cisplatin chemotherapy.
Efficacy and Safety of Tinengotinib in Patients With Advanced Refractory/Relapsed CCA Who Previously Received an FGFR Inhibitor
2023 Year in Review: Cholangiocarcinoma
Investigators pooled data from 3 trials to evaluate tinengotinib in patients with advanced, refractory/relapsed cholangiocarcinoma who previously received an FGFR inhibitor.
KLF5 Inhibition Reduces Tumor Growth and Sensitizes to Chemotherapy-Induced Cell Death in Experimental Models of CCA
2023 Year in Review: Cholangiocarcinoma
Researchers evaluated KLF5 expression and its inhibition in cholangiocarcinoma using clustered regularly interspaced short palindromic repeats technology.
Phase 2 Trial of SHR-1316 Plus IBI310 in Patients With Advanced iCCA After Inadequate Response to First-Line Therapy
2023 Year in Review: Cholangiocarcinoma
In this ongoing phase 2 study, the efficacy of SHR-1316 plus IBI310 is being evaluated in patients with advanced intrahepatic cholangiocarcinoma after inadequate response to first-line therapy.
Examination of Patients With CCA Treated With Novel Targeted Therapies After Extended Molecular Profiling on Liquid Biopsies
2023 Year in Review: Cholangiocarcinoma
Dr Mahmood presented results from the largest multi-institutional review of efficacy outcomes following targeted agents in patients with cholangiocarcinoma.
Phase 2 Component of the BEER-BTC Study: Comparing Bevacizumab Plus Erlotinib Maintenance Versus Observation in Patients With Advanced BTC
2023 Year in Review: Cholangiocarcinoma
In the phase 2 component of the phase 2/3 BEER-BTC study, bevacizumab plus erlotinib improved outcomes in patients with advanced biliary tract cancers.
The DEBATE Trial: Neoadjuvant Durvalumab Plus GemCis Versus GemCis Alone for Patients With Localized BTC
2023 Year in Review: Cholangiocarcinoma
Researchers investigated the efficacy and safety of neoadjuvant durvalumab plus gemcitabine/cisplatin (GemCis) versus GemCis alone in patients with biliary tract cancer.

Subscribe Today!

To sign up for our newsletter or print publications, please enter your contact information below.

I'd like to receive: