Trametinib in combination with hydroxychloroquine or palbociclib in advanced metastatic pancreatic cancer: data from a retrospective, multicentric cohort (AIO AIO-TF/PAK-0123).

Humans Pancreatic Neoplasms / drug therapy Male Middle Aged Retrospective Studies Female Aged Pyridones / administration & dosage Antineoplastic Combined Chemotherapy Protocols / therapeutic use Pyrimidinones / administration & dosage Pyridines / therapeutic use Hydroxychloroquine / therapeutic use Piperazines / therapeutic use Adult Aged, 80 and over

Autophagy CDK inhibitor MEK inhibitor Molecular guided treatment Pancreatic cancer Targeted therapy

Journal

Journal of cancer research and clinical oncology

ISSN: 1432-1335

Titre abrégé: J Cancer Res Clin Oncol

Pays: Germany

ID NLM: 7902060

Informations de publication

Date de publication:
01 Oct 2024

Historique:

received: 24 07 2024

accepted: 13 09 2024

medline: 1 10 2024

pubmed: 1 10 2024

entrez: 1 10 2024

Statut: epublish

Résumé

Preclinical 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. In 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. Overall, 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. THCQ and TP are not effective in patients with advanced PDAC harboring KRAS mutations or alterations in MAPK/CDKN2A/B.

Sections du résumé

BACKGROUND BACKGROUND

METHODS METHODS

In 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.

RESULTS RESULTS

Overall, 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.

CONCLUSION CONCLUSIONS

THCQ and TP are not effective in patients with advanced PDAC harboring KRAS mutations or alterations in MAPK/CDKN2A/B.

Identifiants

DOI: 10.1007/s00432-024-05954-5 PMID: 39352477

pubmed: 39352477

doi: 10.1007/s00432-024-05954-5

pii: 10.1007/s00432-024-05954-5

doi:

Substances chimiques

palbociclib G9ZF61LE7G

Pyridones 0

trametinib 33E86K87QN

Pyrimidinones 0

Pyridines 0

Hydroxychloroquine 4QWG6N8QKH

Piperazines 0

Types de publication

Journal Article Multicenter Study

Langues

eng

Sous-ensembles de citation

Pagination

438

Informations de copyright

Références

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