ATM or CHEK2 alterations: Potential biomarkers of improved outcomes with irinotecan-containing chemotherapy in advanced pancreatic ductal adenocarcinoma

Autor: Maahum Mehdi, Bicky Thapa, Aniko Szabo, Gulrayz Ahmed, Aditya V. Shreenivas, James P. Thomas, Deepika Sriram, Douglas B. Evans, Susan Tsai, Kathleen K. Christians, Beth Erickson, William A. Hall, Thomas McFall, Steve Patrick, Ben George, Razelle Kurzrock, Mandana Kamgar
Rok vydání: 2023
Předmět:
Zdroj: Journal of Clinical Oncology. 41:754-754
ISSN: 1527-7755
0732-183X
Popis: 754 Background: ATM and CHEK2 mutations are linked to homologous recombination DNA repair deficiency, with the potential for improved therapeutic response to DNA damaging agents. To investigate our clinical observation of improved outcomes with irinotecan (IRI) based chemotherapy in advanced/metastatic pancreatic ductal adenocarcinoma (PDAC) patients (pts) with somatic or germline ATM/ CHEK2 mutations, we examined our institutional real world experience. Methods: Between 2015-2021, 33 pts with ATM or CHEK2 mutations treated with chemotherapy were identified, of which 16 pts had advanced/metastatic disease. Progression-free survival (PFS) was calculated and compared (Kaplan Meier, log-rank test) in several ways to assess the impact of IRI vs platinum or other regimens. The event for PFS was progression (or death), and pts without progression were censored at treatment end, or at last follow up if treatment was ongoing. Results: Among 16 pts with advanced/metastatic PDAC, 8 (50%) had ATM (5 germline, 3 somatic) and 8 (50%), CHEK2 alterations (4 germline, 4 somatic). Overall, pts received 48 lines of chemotherapy (platinum-based-(No-IRI) N=14; IRI-based-(No-Platinum) N=8; both N=4; none N=22). For best-PFS among pts analysis, median line of best-PFS therapy for IRI-Ever (N=9 pts) was 2nd line (range 1-7) and for IRI-Never (N=7 pts) was 1st (range, 1-1); median PFS was 13 vs 3 months (mo) (IRI-Ever vs IRI-Never; p=0.0076). For PFS analysis within lines of treatment of each pt, median therapy line for both IRI-containing and No-IRI lines was 2nd line (range 1-7); median PFS for IRI-containing (N=12 lines of therapy) vs No-IRI (N=36) was 12.1 vs 3 mo (p
Databáze: OpenAIRE
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