Witte, David and Pretzell, Ina and Reissig, Timm M. and Stein, Alexander and Velthaus, Janna-Lisa and Alig, Annabel and Bohnenberger, Hanibal and Knoedler, Maren and Kurreck, Annika and Sulzer, Sabrina and Beyer, Georg and Dorman, Klara and Frohlich, Tabea and Hegenberg, Stefanie and Lugnier, Celine and Saborowski, Anna and Vogel, Arndt and Lange, Sebastian and Reichert, Maximilian and Flade, Franziska and Klaas, Lioba and Utpatel, Kirsten and Becker, Heiko and Bleckmann, Annalen and Wethmar, Klaus and Reinacher-Schick, Anke and Westphalen, Christoph Benedikt (2024) Trametinib in combination with hydroxychloroquine or palbociclib in advanced metastatic pancreatic cancer: data from a retrospective, multicentric cohort (AIO AIO-TF/PAK-0123). JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY, 150 (10): 438. ISSN 0171-5216, 1432-1335
Full text not available from this repository. (Request a copy)Abstract
BackgroundPreclinical models of pancreatic cancer (PDAC) suggest a synergistic role for combined MEK and autophagy signaling inhibition, as well as MEK and CDK4/6 pathway targeting. Several case reports implicate clinical activity of the combination of either trametinib and hydroxychloroquine (HCQ) in patients with KRAS-mutant PDAC or trametinib with CDK4/6 inhibitors in patients with KRAS and CDKN2A/B alterations. However, prospective data from clinical trials is lacking. Here, we aim to provide clinical evidence regarding the use of these experimental regimens in the setting of dedicated precision oncology programs.MethodsIn this retrospective case series, PDAC patients who received either trametinib/HCQ (THCQ) or trametinib/palbociclib (TP) were retrospectively identified across 11 participating cancer centers in Germany.ResultsOverall, 34 patients were identified. 19 patients received THCQ, and 15 received TP, respectively. In patients treated with THCQ, the median duration of treatment was 46 days, median progression-free survival (PFS) was 52 days and median overall survival (OS) was 68 days. In the THCQ subgroup, all patients evaluable for response (13/19) had progressive disease (PD) within 100 days. In the TP subgroup, the median duration of treatment was 60 days, median PFS was 56 days and median OS was 195 days. In the TP subgroup, 9/15 patients were evaluable for response, of which 1/9 showed a partial response (PR) while 8/9 had PD. One patient achieved a clinical benefit despite progression under TP.ConclusionTHCQ and TP are not effective in patients with advanced PDAC harboring KRAS mutations or alterations in MAPK/CDKN2A/B.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | POSITIVE SOLID TUMORS; INHIBITOR; CDK4/6; LUNG; KRAS; MEK; Pancreatic cancer; MEK inhibitor; CDK inhibitor; Autophagy; Targeted therapy; Molecular guided treatment |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Pathologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 14 Aug 2025 06:46 |
| Last Modified: | 14 Aug 2025 06:46 |
| URI: | https://pred.uni-regensburg.de/id/eprint/65645 |
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