Publication
Title
Efficacy and safety of abemaciclib alone and with PI3K/mTOR inhibitor LY3023414 or galunisertib versus chemotherapy in previously treated metastatic pancreatic adenocarcinoma : a randomized controlled trial
Author
Abstract
Background: Pancreatic ductal adenocarcinomas (PDAC) are characterized by frequent cell cycle pathways aberrations. This study evaluated safety and efficacy of abemaciclib, a cyclin-dependent kinase 4 and 6 inhibitor, as monotherapy or in combination with PI3K/mTOR dual inhibitor LY3023414 or TGF beta inhibitor galunisertib versus standard of care (SOC) chemotherapy in patients with pretreated metastatic PDAC.Methods: This Phase 2 open-label study enrolled patients with metastatic PDAC who progressed after 1-2 prior therapies. Patients were enrolled in a safety lead-in (abemaciclib plus galunisertib) followed by a 2-stage randomized design. Stage 1 randomization was planned 1:1:1:1 for abemaciclib, abemaciclib plus LY3023414, abemaciclib plus galunisertib, or SOC gemcitabine or capecitabine. Advancing to Stage 2 required a disease control rate (DCR) difference >= 0 in abemaciclib-containing arms versus SOC. Primary objectives for Stages 1 and 2 were DCR and progression-free survival (PFS), respectively. Secondary objectives included response rate, overall survival, safety, and pharmacokinetics.Results: One hundred and six patients were enrolled. Abemaciclib plus galunisertib did not advance to Stage 1 for reasons unrelated to safety or efficacy. Stage 1 DCR was 15.2% with abemaciclib monotherapy, 12.1% with abemaciclib plus LY3023414, and 36.4% with SOC. Median PFS was 1.7 months (95% CI: 1.4-1.8), 1.8 months (95% CI: 1.3-1.9), and 3.3 months (95% CI: 1.1-5.7), respectively. No arms advanced to Stage 2. No new safety signals were identified.Conclusion: In patients with pretreated metastatic PDAC, abemaciclib-based therapy did not improve DCRs or PFS compared with SOC chemotherapy. No treatment arms advanced to Stage 2. Abemaciclib remains investigational in patients with PDAC.
Language
English
Source (journal)
Cancer Medicine
Publication
Hoboken : Wiley , 2023
ISSN
2045-7634
DOI
10.1002/CAM4.6621
Volume/pages
12 :20 (2023) , p. 20353-20364
ISI
001084869300001
Pubmed ID
37840530
Full text (Publisher's DOI)
Full text (open access)
UAntwerpen
Faculty/Department
Research group
Publication type
Subject
Affiliation
Publications with a UAntwerp address
External links
Web of Science
Record
Identifier
Creation 04.12.2023
Last edited 07.12.2023
To cite this reference