Chemotherapy-free treatment targeting fusions and driver mutations in KRAS wild-type pancreatic ductal adenocarcinoma, a case series. Ther Adv Med Oncol 2024;16:17588359241253113
Date
05/21/2024Pubmed ID
38770091Pubmed Central ID
PMC11104030DOI
10.1177/17588359241253113Scopus ID
2-s2.0-85193752803 (requires institutional sign-in at Scopus site) 5 CitationsAbstract
BACKGROUND: KRAS wild-type (WT) pancreatic ductal adenocarcinoma (PDAC) represents a distinct entity with unique biology. The therapeutic impact of matched targeted therapy in these patients in a real-world setting, to date, is less established.
OBJECTIVES: The aim of our study was to review our institutional database to identify the prevalence of actionable genomic alterations in patients with KRAS-WT tumors and to evaluate the therapeutic impact of matched targeted therapy in these patients.
DESIGN: We reviewed electronic medical records of patients with KRAS-WT PDAC and advanced disease (n = 14) who underwent clinical-grade tissue ± liquid next-generation sequencing (315-648 genes for tissue) between years 2015 and 2021.
METHODS: Demographic and disease characteristics were summarized using descriptive parameters. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method.
RESULTS: Of 236 PDAC patients, 14 had advanced/metastatic disease with KRAS-WT tumors. Median age at diagnosis was 66 years. There was a high frequency of potentially actionable genomic alterations, including three (21%) with BRAF alterations, two (14%) with fusions [RET-PCM1 and FGFR2-POC1B (N = 1 each)]; and one with a druggable EGFR (EGFR E746_A755delISERD) variant; two other patients had an STK11 and a MUTYH alteration. Five patients were treated with matched targeted therapy, with three having durable benefit: (i) erlotinib for EGFR-altered tumor, followed by osimertinib/capmatinib when MET amplification emerged (first-line therapy); (ii) pralsetinib for RET fusion (fifth line); and (iii) dabrafenib/trametinib for BRAF N486_P490del (third line). Duration of time on chemotherapy-free matched targeted therapy for these patients was 17+, 11, and 18+ months, respectively.
CONCLUSION: Sustained therapeutic benefit can be achieved in a real-world setting in a subset of patients with advanced/metastatic KRAS-WT PDAC treated with chemotherapy-free matched targeted agents. Prospective studies are warranted.
Author List
Mehdi M, Szabo A, Shreenivas A, Thomas JP, Tsai S, Christians KK, Evans DB, Clarke CN, Hall WA, Erickson B, Ahmed G, Thapa B, McFall T, George B, Kurzrock R, Kamgar MAuthors
Kathleen K. Christians MD Professor in the Surgery department at Medical College of WisconsinCallisia N. Clarke MD Chief, Associate Professor in the Surgery department at Medical College of Wisconsin
Beth A. Erickson MD Professor in the Radiation Oncology department at Medical College of Wisconsin
Douglas B. Evans MD Chair, Professor in the Surgery department at Medical College of Wisconsin
William Adrian Hall MD Chair, Professor in the Radiation Oncology department at Medical College of Wisconsin
Mandana Kamgar MPH, MD Associate Professor in the Medicine department at Medical College of Wisconsin
Razelle Kurzrock MD Center Associate Director, Professor in the Medicine department at Medical College of Wisconsin
Thomas Mcfall PhD Assistant Professor in the Biochemistry department at Medical College of Wisconsin
Aniko Szabo PhD Professor in the Data Science Institute department at Medical College of Wisconsin
James P. Thomas PhD, MD Professor in the Medicine department at Medical College of Wisconsin
