EUS-FNA Biopsies to Guide Precision Medicine in Pancreatic Cancer: Results of a Pilot Study to Identify KRAS Wild-Type Tumours for Targeted Therapy

Frontiers in Oncology

Val Gebski¹  Adina Borsaru²  Michael Swan³  Christopher Desmond³  Daniel Croagh⁴  Allan Zimet⁷  David Goldstein⁸  Brendan J. Jenkins⁹  Marion Harris^1,10  Joanne Lundy^1,11  John Zalcberg^1,13 

[1] 0National Health and Medical Research Council Clinical Trials Centre, University of Sydney, Camperdown, NSW, Australia;1Diagnostic Imaging, Monash Health, Melbourne, VIC, Australia;2Department of Gastroenterology, Monash Health, Melbourne, VIC, Australia;3Department of Surgery, Epworth Healthcare, Melbourne, VIC, Australia;Centre for Innate Immunity and Infectious Diseases, Hudson Institute of Medical Research, Clayton, VIC, Australia;Department of Medical Oncology, Alfred Health, Melbourne, VIC, Australia;Department of Medical Oncology, Epworth Hospital, Melbourne, VIC, Australia;Department of Medical Oncology, Prince of Wales Hospital, Randwick, NSW, Australia;Department of Molecular and Translational Science, Faculty of Medicine, Nursing and Health Sciences, Monash University, Clayton, VIC, Australia;Department of Oncology, Faculty of Medicine, Nursing and Health Sciences and School of Clinical Sciences, Monash University, Clayton, VIC, Australia;Department of Surgery, Faculty of Medicine, Nursing and Health Sciences, Monash University, Clayton, VIC, Australia;Prince of Wales Clinical School, University of New South Wales, Sydney, NSW, Australia;Public Health and Preventative Medicine, Monash University, Melbourne, VIC, Australia;

关键词: pancreatic cancer;    endoscopic ultrasound;    KRAS;    molecular analysis;    precision medicine;   

DOI  :  10.3389/fonc.2021.770022

来源: DOAJ

【 摘 要 】

BackgroundPancreatic ductal adenocarcinoma (PDAC) is a leading cause of cancer death and lacks effective treatment options. Diagnostic endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) biopsies represent an appealing source of material for molecular analysis to inform targeted therapy, as they are often the only available tissue for patients presenting with PDAC irrespective of disease stage. However, EUS-FNA biopsies are typically not used to screen for precision medicine studies due to concerns about low tissue yield and quality. Epidermal growth factor receptor (EGFR) inhibition has shown promise in clinical trials of unselected patients with advanced pancreatic cancer, but has not been prospectively tested in KRAS wild-type patients. Here, we examine the clinical utility of EUS-FNA biopsies for molecular screening of KRAS wild-type PDAC patients for targeted anti-EGFR therapy to assess the feasibility of this approach.Patients and MethodsFresh frozen EUS-FNA or surgical biopsies from PDAC patient tumours were used to screen for KRAS mutations. Eligible patients with recurrent, locally advanced, or metastatic KRAS wild-type status who had received at least one prior line of chemotherapy were enrolled in a pilot study (ACTRN12617000540314) and treated with panitumumab at 6mg/kg intravenously every 2 weeks until progression or unacceptable toxicity. The primary endpoint was 4-month progression-free survival (PFS).Results275 patient biopsies were screened for KRAS mutations, which were detected in 88.3% of patient samples. 8 eligible KRAS wild-type patients were enrolled onto the interventional study between November 2017 and December 2020 and treated with panitumumab. 4-month PFS was 14.3% with no objective tumour responses observed. The only grade 3/4 treatment related toxicity observed was hypomagnesaemia.ConclusionsThis study demonstrates proof-of-principle feasibility to molecularly screen patients with pancreatic cancer for targeted therapies, and confirms diagnostic EUS-FNA biopsies as a reliable source of tumour material for molecular analysis. Single agent panitumumab was safe and tolerable but led to no objective tumour responses in this population.

【 授权许可】

Unknown