FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W4322771246> ?p ?o ?g. }

• W4322771246 endingPage "08" @default.
• W4322771246 startingPage "P1" @default.
• W4322771246 abstract "Abstract Background Previously, we reported the clinical outcomes of the combination of anti-PD-1 Ab, cyclin-dependent kinase 4/6 inhibitors, and endocrine therapy (ET) in patients with ER positive/HER2 negative advanced breast cancer in SABCS2020; biomarker analysis has been performed to provide insight into the hepatotoxicy frequently observed in the study. Methods Subjects received 240 mg nivolumab IV on days 1 and 15, 150 mg abemaciclib PO twice daily, and either 500 mg fulvestrant (FUL) on days 1, 15, 29, and every 4 weeks thereafter (FUL cohort) or 2.5 mg letrozole (LET) once daily (LET cohort). The primary endpoint was objective response rate and secondary endpoints included toxicity evaluated in the CTCAE along with an exploratory endpoint as related to the biomarker analysis. Archival tumor tissues were collected before study entry and blood and stool samples were collected at baseline and on cycle3 day1. Tumor tissues were subjected to IHC analysis and RNA sequencing followed by subtyping using NGS. High throughput cytokine analysis using ELISA-based assay were performed with serum samples and cell sorting analysis of PBMC was performed with FACS. Results From June 2019 to December 2019, 17 subjects were enrolled (FUL cohort [n = 12], LET cohort [n = 5]). The study was prematurely closed due to safety concerns such as hepatotoxicity and interstitial lung disease. AEs ≥ Grade 3 were observed in 91.7% and 100% of patients in the FUL and LET cohorts, respectively. The most frequent AEs ≥ Grade 3 were elevated liver function tests (LFT; FUL cohort: 50.0%, LET cohort: 60.0%). Serum cytokine analysis from the subjects with severe hepatotoxicity indicated cytokine storm with elevations of sCD30/TNFRSF8, IL-11, -34, Pentraxin-3, sTNF-R1, -R2, TSLP, which was supported by the findings of reduction of effector regulatory T cells in PBMC. IHC study in liver biopsy from three subjects with the toxicity revealed infiltration of CD8+ T cells and FOXP3+ T reg into the liver, suggesting the immune related liver injury upon the treatment with nivolumab and abemaciclib. HLA typing was performed in the 17 patients but no association between HLA type and ILD or hepatotoxicity were observed. Conclusions The frequent and severe immune related hepatotoxicity induced by the combination of anti-DD-1 and CDK 4/6 inhibitors might have been an immune-boosting therapy as suggested in the preclinical studies. This study was supported by the Ono Pharmaceutical Co., LTD. The registration number of the study is UMIN000036970. Citation Format: Junji Tsurutani, Jun Masuda, Norikazu Masuda, Yuko Tanabe, Tsutomu Iwasa, Masato Takahashi, Manabu Futamura, Koji Matsumoto, Kenjiro Aogi, Hiroji Iwata, Mari Hosonaga, Toru Mukohara, Kiyoshi Yoshimura, Chiyo K. Imamura, Sakiko Miura, Toshiko Yamochi, Kenichi Yoshimura, Toshimi Takano, Hidetaka Kawabata. Biomarker analysis of hepatotoxicity in a Phase II study of nivolumab, abemaciclib and endocrine therapy in patients with HR-positive, HER2-negative breast cancer: WJOG11418BTR NEWFLAME_TR [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P1-12-08." @default.
• W4322771246 created "2023-03-03" @default.
• W4322771246 creator A5004862046 @default.
• W4322771246 creator A5008946028 @default.
• W4322771246 creator A5009160170 @default.
• W4322771246 creator A5011017659 @default.
• W4322771246 creator A5012322249 @default.
• W4322771246 creator A5016197648 @default.
• W4322771246 creator A5021379709 @default.
• W4322771246 creator A5022386220 @default.
• W4322771246 creator A5030591160 @default.
• W4322771246 creator A5041726660 @default.
• W4322771246 creator A5044214575 @default.
• W4322771246 creator A5057467660 @default.
• W4322771246 creator A5067189124 @default.
• W4322771246 creator A5067561532 @default.
• W4322771246 creator A5071061939 @default.
• W4322771246 creator A5072348132 @default.
• W4322771246 creator A5079050158 @default.
• W4322771246 creator A5090361588 @default.
• W4322771246 creator A5091499529 @default.
• W4322771246 date "2023-03-01" @default.
• W4322771246 modified "2023-10-13" @default.
• W4322771246 title "Abstract P1-12-08: Biomarker analysis of hepatotoxicity in a Phase II study of nivolumab, abemaciclib and endocrine therapy in patients with HR-positive, HER2-negative breast cancer: WJOG11418BTR NEWFLAME_TR" @default.
• W4322771246 doi "https://doi.org/10.1158/1538-7445.sabcs22-p1-12-08" @default.
• W4322771246 hasPublicationYear "2023" @default.
• W4322771246 type Work @default.
• W4322771246 citedByCount "0" @default.
• W4322771246 crossrefType "journal-article" @default.
• W4322771246 hasAuthorship W4322771246A5004862046 @default.
• W4322771246 hasAuthorship W4322771246A5008946028 @default.
• W4322771246 hasAuthorship W4322771246A5009160170 @default.
• W4322771246 hasAuthorship W4322771246A5011017659 @default.
• W4322771246 hasAuthorship W4322771246A5012322249 @default.
• W4322771246 hasAuthorship W4322771246A5016197648 @default.
• W4322771246 hasAuthorship W4322771246A5021379709 @default.
• W4322771246 hasAuthorship W4322771246A5022386220 @default.
• W4322771246 hasAuthorship W4322771246A5030591160 @default.
• W4322771246 hasAuthorship W4322771246A5041726660 @default.
• W4322771246 hasAuthorship W4322771246A5044214575 @default.
• W4322771246 hasAuthorship W4322771246A5057467660 @default.
• W4322771246 hasAuthorship W4322771246A5067189124 @default.
• W4322771246 hasAuthorship W4322771246A5067561532 @default.
• W4322771246 hasAuthorship W4322771246A5071061939 @default.
• W4322771246 hasAuthorship W4322771246A5072348132 @default.
• W4322771246 hasAuthorship W4322771246A5079050158 @default.
• W4322771246 hasAuthorship W4322771246A5090361588 @default.
• W4322771246 hasAuthorship W4322771246A5091499529 @default.
• W4322771246 hasConcept C121608353 @default.
• W4322771246 hasConcept C126322002 @default.
• W4322771246 hasConcept C143998085 @default.
• W4322771246 hasConcept C185592680 @default.
• W4322771246 hasConcept C203092338 @default.
• W4322771246 hasConcept C2775930923 @default.
• W4322771246 hasConcept C2777176818 @default.
• W4322771246 hasConcept C2777701055 @default.
• W4322771246 hasConcept C2778812593 @default.
• W4322771246 hasConcept C2780030458 @default.
• W4322771246 hasConcept C2780482068 @default.
• W4322771246 hasConcept C2781197716 @default.
• W4322771246 hasConcept C530470458 @default.
• W4322771246 hasConcept C535046627 @default.
• W4322771246 hasConcept C55493867 @default.
• W4322771246 hasConcept C71924100 @default.
• W4322771246 hasConcept C72563966 @default.
• W4322771246 hasConcept C84606932 @default.
• W4322771246 hasConcept C90924648 @default.
• W4322771246 hasConceptScore W4322771246C121608353 @default.
• W4322771246 hasConceptScore W4322771246C126322002 @default.
• W4322771246 hasConceptScore W4322771246C143998085 @default.
• W4322771246 hasConceptScore W4322771246C185592680 @default.
• W4322771246 hasConceptScore W4322771246C203092338 @default.
• W4322771246 hasConceptScore W4322771246C2775930923 @default.
• W4322771246 hasConceptScore W4322771246C2777176818 @default.
• W4322771246 hasConceptScore W4322771246C2777701055 @default.
• W4322771246 hasConceptScore W4322771246C2778812593 @default.
• W4322771246 hasConceptScore W4322771246C2780030458 @default.
• W4322771246 hasConceptScore W4322771246C2780482068 @default.
• W4322771246 hasConceptScore W4322771246C2781197716 @default.
• W4322771246 hasConceptScore W4322771246C530470458 @default.
• W4322771246 hasConceptScore W4322771246C535046627 @default.
• W4322771246 hasConceptScore W4322771246C55493867 @default.
• W4322771246 hasConceptScore W4322771246C71924100 @default.
• W4322771246 hasConceptScore W4322771246C72563966 @default.
• W4322771246 hasConceptScore W4322771246C84606932 @default.
• W4322771246 hasConceptScore W4322771246C90924648 @default.
• W4322771246 hasIssue "5_Supplement" @default.
• W4322771246 hasLocation W43227712461 @default.
• W4322771246 hasOpenAccess W4322771246 @default.
• W4322771246 hasPrimaryLocation W43227712461 @default.
• W4322771246 hasRelatedWork W2100085165 @default.
• W4322771246 hasRelatedWork W2593892593 @default.
• W4322771246 hasRelatedWork W2690569173 @default.
• W4322771246 hasRelatedWork W2747078758 @default.
• W4322771246 hasRelatedWork W2751810360 @default.
• W4322771246 hasRelatedWork W2931385471 @default.
• W4322771246 hasRelatedWork W3031130887 @default.
• W4322771246 hasRelatedWork W4226356606 @default.

• next