Matches in SemOpenAlex for { <https://semopenalex.org/work/W2947102964> ?p ?o ?g. }
Showing items 1 to 97 of
97
with 100 items per page.
- W2947102964 endingPage "3551" @default.
- W2947102964 startingPage "3551" @default.
- W2947102964 abstract "3551 Background: Agents targeting the angiogenic pathway have been a cornerstone therapy in mCRC. In chemo-refractory mCRC, RGF, an oral multikinase inhibitor with considerable angiogenic inhibition, has shown modest effects on survival. We reported that autophagy modulation using the autophagy inhibitor, HCQ, enhances the anti-cancer activity of the histone deacetylase inhibitor, VOR, via ubiquitinated protein accumulation in CRC. A phase 1b study confirmed VOR/HCQ is active and tolerated in refractory mCRC. We conducted a prospective randomized study to evaluate efficacy of VOR/HCQ vs RGF in mCRC patients (NCT02316340) and report a planned interim analysis. Methods: Randomized, controlled trial of VOR 400 mg and HCQ 600 mg PO daily vs RGF 160 mg PO daily (3 weeks on, 1 week off), Q4weeks, in advanced CRC patients. Crossover was optional after first progression. A total of 76 patients are planned. Primary endpoint: mPFS. Secondary endpoints: mOS; adverse events (NCI-CTCAEv3.0); PD analysis: 27-plex Human Cytokine Array, NGS analysis (Guardant Health) on cell-free, ctDNA. Results: At interim analysis, n = 42 patients enrolled from 2/2015-10/2017: n = 20 VOR/HCQ (5 crossed to RGF), n = 22 RGF (13 crossed to VOR/HCQ). 38 patients evaluable (at least C1 completed). Median age 58.4, 40% NH vs 60% H. mPFS on first arm: 1.90 mo VOR/HCQ vs 4.35 mo RGF [p = 0.032, HR: 2.277]. mOS: 6.77 mo VOR/HCQ vs 7.23 mo RGF [p = 0.90, HR: 1.05]. Grade 3/4 AEs (see table). In both arms, there was trend towards decreased IL-1b, IL-2, IL-6, IL-10, TNFα, IFNγ but an increase in GM-CSF after treatment. Responders (4+ cycles) had lower baseline Max MAF versus nonresponders for both arms. In responders, there was trend toward a decrease in Max MAF at C2 and then increase at progression. Conclusions: VOR/HCQ did not improve survival when compared to RGF. VOR/HCQ has a favorable safety profile, but further planned subgroup analysis is pending to identify biomarkers of efficacy in responders. Clinical trial information: NCT02316340. [Table: see text]" @default.
- W2947102964 created "2019-06-07" @default.
- W2947102964 creator A5004814161 @default.
- W2947102964 creator A5019498881 @default.
- W2947102964 creator A5028433300 @default.
- W2947102964 creator A5056309801 @default.
- W2947102964 creator A5057503413 @default.
- W2947102964 creator A5071147268 @default.
- W2947102964 creator A5073249476 @default.
- W2947102964 creator A5088077636 @default.
- W2947102964 date "2019-05-20" @default.
- W2947102964 modified "2023-10-18" @default.
- W2947102964 title "Modulation of autophagy: A phase II study of vorinostat (VOR) plus hydroxychloroquine (HCQ) vs regorafenib (RGF) in chemo-refractory metastatic colorectal cancer (mCRC)." @default.
- W2947102964 doi "https://doi.org/10.1200/jco.2019.37.15_suppl.3551" @default.
- W2947102964 hasPublicationYear "2019" @default.
- W2947102964 type Work @default.
- W2947102964 sameAs 2947102964 @default.
- W2947102964 citedByCount "7" @default.
- W2947102964 countsByYear W29471029642020 @default.
- W2947102964 countsByYear W29471029642022 @default.
- W2947102964 countsByYear W29471029642023 @default.
- W2947102964 crossrefType "journal-article" @default.
- W2947102964 hasAuthorship W2947102964A5004814161 @default.
- W2947102964 hasAuthorship W2947102964A5019498881 @default.
- W2947102964 hasAuthorship W2947102964A5028433300 @default.
- W2947102964 hasAuthorship W2947102964A5056309801 @default.
- W2947102964 hasAuthorship W2947102964A5057503413 @default.
- W2947102964 hasAuthorship W2947102964A5071147268 @default.
- W2947102964 hasAuthorship W2947102964A5073249476 @default.
- W2947102964 hasAuthorship W2947102964A5088077636 @default.
- W2947102964 hasConcept C104317684 @default.
- W2947102964 hasConcept C121608353 @default.
- W2947102964 hasConcept C126322002 @default.
- W2947102964 hasConcept C143998085 @default.
- W2947102964 hasConcept C168563851 @default.
- W2947102964 hasConcept C183713625 @default.
- W2947102964 hasConcept C185592680 @default.
- W2947102964 hasConcept C190283241 @default.
- W2947102964 hasConcept C197934379 @default.
- W2947102964 hasConcept C203092338 @default.
- W2947102964 hasConcept C2776262904 @default.
- W2947102964 hasConcept C2776694085 @default.
- W2947102964 hasConcept C2776820818 @default.
- W2947102964 hasConcept C2777802072 @default.
- W2947102964 hasConcept C2778305200 @default.
- W2947102964 hasConcept C2778375690 @default.
- W2947102964 hasConcept C526805850 @default.
- W2947102964 hasConcept C55493867 @default.
- W2947102964 hasConcept C61943457 @default.
- W2947102964 hasConcept C64927066 @default.
- W2947102964 hasConcept C71924100 @default.
- W2947102964 hasConcept C86554907 @default.
- W2947102964 hasConcept C90924648 @default.
- W2947102964 hasConceptScore W2947102964C104317684 @default.
- W2947102964 hasConceptScore W2947102964C121608353 @default.
- W2947102964 hasConceptScore W2947102964C126322002 @default.
- W2947102964 hasConceptScore W2947102964C143998085 @default.
- W2947102964 hasConceptScore W2947102964C168563851 @default.
- W2947102964 hasConceptScore W2947102964C183713625 @default.
- W2947102964 hasConceptScore W2947102964C185592680 @default.
- W2947102964 hasConceptScore W2947102964C190283241 @default.
- W2947102964 hasConceptScore W2947102964C197934379 @default.
- W2947102964 hasConceptScore W2947102964C203092338 @default.
- W2947102964 hasConceptScore W2947102964C2776262904 @default.
- W2947102964 hasConceptScore W2947102964C2776694085 @default.
- W2947102964 hasConceptScore W2947102964C2776820818 @default.
- W2947102964 hasConceptScore W2947102964C2777802072 @default.
- W2947102964 hasConceptScore W2947102964C2778305200 @default.
- W2947102964 hasConceptScore W2947102964C2778375690 @default.
- W2947102964 hasConceptScore W2947102964C526805850 @default.
- W2947102964 hasConceptScore W2947102964C55493867 @default.
- W2947102964 hasConceptScore W2947102964C61943457 @default.
- W2947102964 hasConceptScore W2947102964C64927066 @default.
- W2947102964 hasConceptScore W2947102964C71924100 @default.
- W2947102964 hasConceptScore W2947102964C86554907 @default.
- W2947102964 hasConceptScore W2947102964C90924648 @default.
- W2947102964 hasIssue "15_suppl" @default.
- W2947102964 hasLocation W29471029641 @default.
- W2947102964 hasOpenAccess W2947102964 @default.
- W2947102964 hasPrimaryLocation W29471029641 @default.
- W2947102964 hasRelatedWork W2051540233 @default.
- W2947102964 hasRelatedWork W2119565846 @default.
- W2947102964 hasRelatedWork W2170601050 @default.
- W2947102964 hasRelatedWork W2276886184 @default.
- W2947102964 hasRelatedWork W2329621221 @default.
- W2947102964 hasRelatedWork W2546154929 @default.
- W2947102964 hasRelatedWork W2894779831 @default.
- W2947102964 hasRelatedWork W2955181235 @default.
- W2947102964 hasRelatedWork W2972537131 @default.
- W2947102964 hasRelatedWork W4226051264 @default.
- W2947102964 hasVolume "37" @default.
- W2947102964 isParatext "false" @default.
- W2947102964 isRetracted "false" @default.
- W2947102964 magId "2947102964" @default.
- W2947102964 workType "article" @default.