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CALGB 80303: Genome-Wide Association Study of Advanced Pancreatic Cancer Patients

ABSTRACT:

CALGB 80303 was a randomized, phase III study in advanced pancreatic cancer patients treated with Gemcitabine plus either Bevacizumab or placebo. No difference in overall survival (OS) was observed between the two arms. We prospectively collected germline DNA and conducted a genome-wide association study (GWAS).

PROVIDER: phs000250 | dbGaP |

SECONDARY ACCESSION(S): PRJNA75655PRJNA75653

REPOSITORIES: dbGaP

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			Action	DRS
	GapExchange_phs000250.v1.p1.xml	Xml
	dbGaPEx2.1.5.xsd	Other
	Study_Report.phs000250.NIGMS_CALGB_80303.v1.p1.MULTI.pdf	Pdf
	manifest_phs000250.NIGMS_CALGB_80303.v1.p1.c1.APTC.pdf	Pdf
	datadict_v2.xsl	Other

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CALGB 80303:Genome-Wide Association Study of Advanced Pancreatic Cancer Patients - A Randomized Phase III trial of Gemcitabine Plus Bevacizumab versus Gemcitabine Plus Placebo in Patients with Advanced Pancreatic Cancer

Project description:<p>CALGB 80303 was a randomized, phase III study in advanced pancreatic cancer patients treated with Gemcitabine plus either Bevacizumab or placebo. No difference in overall survival (OS) was observed between the two arms. We prospectively collected germline DNA and conducted a genome-wide association study (GWAS).</p>

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Patients With Proneural Glioblastoma May Derive Overall Survival Benefit From the Addition of Bevacizumab to First-Line Radiotherapy and Temozolomide: Retrospective Analysis of the AVAglio Trial

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Tumor immunogenomic features determine outcomes in metastatic colorectal cancer patients treated with standard-of-care combinations of bevacizumab and cetuximab

Project description:CALGB/SWOG 80405 was a randomized phase III trial in first-line mCRC patients treated with bevacizumab, cetuximab, or both, plus chemotherapy. We tested the effect of tumor immune features on OS. Primary tumors (N=554) were profiled by RNAseq. Immune signatures of macrophages, lymphocytes, TGF-β, INF-γ, wound healing, and cytotoxicity were measured. CIBERSORTx scores of naive and memory B cells, plasma cells, CD8+ T cells, resting and activated memory CD4+ T cells, M0 and M2 macrophages, and activated mast cells were measured. Increased M2 macrophage score (HR 6.30, 95% CI 3.0-12.15) and TGF-β signature expression (HR 1.35, 95% CI 1.05-1.77) were associated with shorter OS. Increased scores of plasma cells (HR 0.55, 95% CI 0.38-0.87) and activated memory CD4+ T cells (HR 0.34, 95% CI 0.16-0.65) were associated with longer OS. Using optimal cutoffs from these four features, patients were categorized as having either 4, 3, 2, or 0-1 beneficial features associated with longer OS, and the median (95% CI) OS decreased from 42.5 (35.8-47.8), to 31.0 (28.8-34.4), 25.2 (20.6-27.9), and 17.7 (13.5-20.4) months respectively (p-value 3.48e-11). New immune features can be further evaluated to improve patient response. They provide the rationale for more effective immunotherapy strategies.

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