Andrew Nixon

Overview:

Andrew Nixon, PhD, MBA (Associate Professor of Medicine) is Director of the Phase I Biomarker Laboratory, which brings together clinical, translational and basic research to pursue the development of novel biomarkers defining mechanisms of sensitivity, resistance, and toxicity to given therapeutic drug classes, particularly anti-angiogenic agents. Additionally, the laboratory has been appointed as a Molecular Reference Laboratory for the Alliance oncology cooperative group, a national clinical trial research group sponsored by the National Cancer Institute. The laboratory has quality control procedures in place to address many of the issues involved in clinical trial research including determination of sample quantity, sample integrity, and sample heterogeneity. We have spent considerable time developing robust assays that utilize limited amounts of specimen while providing high quality data. Multiplex ELISA and gene expression arrays are used to analyze serially collected blood and paraffin samples archived from cancer patient clinical trials. This work has the potential to improve the efficacy and toxicity of current therapies and to guide the development of the next generation of anti-angiogenesis therapies for cancer and other diseases.

Positions:

Professor in Medicine

Medicine, Medical Oncology
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

Ph.D. 1997

Wake Forest University

Grants:

Preclinical and Human Correlative Studies of a Novel Bruton Tyronsine Kinase Inhibitor in Pancreatic Cancer

Administered By
Medicine, Medical Oncology
Awarded By
Department of Defense
Role
Co Investigator
Start Date
End Date

Plasma Angiome and Serum Androgens as Predictors of Overall Survival in Metastatic Prostate Cancer

Administered By
Biostatistics & Bioinformatics
Awarded By
Department of Defense
Role
Partnering PI
Start Date
End Date

(PQA5) 'Dose and Mechanisms of Exercise in Breast Cancer Prevention'

Administered By
Radiation Oncology
Awarded By
National Institutes of Health
Role
Co Investigator
Start Date
End Date

Anti-VEGF in Tumors & Wounds: Efficacy vs Toxicity

Administered By
Medicine, Medical Oncology
Awarded By
National Institutes of Health
Role
Co Investigator
Start Date
End Date

Regulation Of Cyclic Gmp Phosphodiesterase By Gz

Administered By
Pharmacology & Cancer Biology
Awarded By
National Institutes of Health
Role
PI-Fellow
Start Date
End Date

Publications:

Predictive Blood-Based Biomarkers in Patients with Epithelial Ovarian Cancer Treated with Carboplatin and Paclitaxel with or without Bevacizumab: Results from GOG-0218.

PURPOSE: GOG-0218, a double-blind placebo-controlled phase III trial, compared carboplatin and paclitaxel with placebo, bevacizumab followed by placebo, or bevacizumab followed by bevacizumab in advanced epithelial ovarian cancer (EOC). Results demonstrated significantly improved progression-free survival (PFS), but no overall survival (OS) benefit with bevacizumab. Blood samples were collected for biomarker analyses. EXPERIMENTAL DESIGN: Plasma samples were analyzed via multiplex ELISA technology for seven prespecified biomarkers [IL6, Ang-2, osteopontin (OPN), stromal cell-derived factor-1 (SDF-1), VEGF-D, IL6 receptor (IL6R), and GP130]. The predictive value of each biomarker with respect to PFS and OS was assessed using a protein marker by treatment interaction term within the framework of a Cox proportional hazards model. Prognostic markers were identified using Cox models adjusted for baseline covariates. RESULTS: Baseline samples were available from 751 patients. According to our prespecified analysis plan, IL6 was predictive of a therapeutic advantage with bevacizumab for PFS (P = 0.007) and OS (P = 0.003). IL6 and OPN were found to be negative prognostic markers for both PFS and OS (P < 0.001). Patients with high median IL6 levels (dichotomized at the median) treated with bevacizumab had longer PFS (14.2 vs. 8.7 months) and OS (39.6 vs. 33.1 months) compared with placebo. CONCLUSIONS: The inflammatory cytokine IL6 may be predictive of therapeutic benefit from bevacizumab when combined with carboplatin and paclitaxel. Aligning with results observed in patients with renal cancer treated with antiangiogenic therapies, it appears plasma IL6 may also define those patients with EOC more or less likely to benefit from the addition of bevacizumab to standard chemotherapy.
Authors
Alvarez Secord, A; Bell Burdett, K; Owzar, K; Tritchler, D; Sibley, AB; Liu, Y; Starr, MD; Brady, JC; Lankes, HA; Hurwitz, HI; Mannel, RS; Tewari, KS; O'Malley, DM; Gray, H; Bakkum-Gamez, JN; Fujiwara, K; Boente, M; Deng, W; Burger, RA; Birrer, MJ; Nixon, AB
MLA Citation
Alvarez Secord, Angeles, et al. “Predictive Blood-Based Biomarkers in Patients with Epithelial Ovarian Cancer Treated with Carboplatin and Paclitaxel with or without Bevacizumab: Results from GOG-0218.Clin Cancer Res, vol. 26, no. 6, Mar. 2020, pp. 1288–96. Pubmed, doi:10.1158/1078-0432.CCR-19-0226.
URI
https://scholars.duke.edu/individual/pub1427139
PMID
31919136
Source
pubmed
Published In
Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
Volume
26
Published Date
Start Page
1288
End Page
1296
DOI
10.1158/1078-0432.CCR-19-0226

Differential expression of immune related genes in high-grade ovarian serous carcinoma.

OBJECTIVE: To identify novel immunologic targets and biomarkers associated with overall survival (OS) in high-grade serous ovarian cancer (HGSC). METHODS: In this retrospective study, microarray data from 51 HGSC specimens were analyzed (Affymetrix HG-U133A). A panel of 183 immune/inflammatory response related genes linked to 279 probe sets was constructed a priori and screened. Associations between gene expression and OS were assessed using logrank tests. Multiple testing was addressed within the False Discovery Rate (FDR) framework. For external validation, TCGA Ovarian dataset and five GSE publicly available HGSC datasets were evaluated. RESULTS: In Duke data, 110 probe sets linked to 83 immunologic/inflammatory-related genes were differentially expressed in tumors from long versus short-term HGSC survivors (adjusted p < 0.05). In TCGA, concordant with the results from the Duke discovery cohort, high expression of one probe (IL6R) demonstrated a consistent significance and concordant association with higher expression in long-term HGSC survivors (Duke q-value = 0.022) and improved OS in the TCGA dataset (p-value = 0.015, HR = 0.8). Thirteen genes in GSE14764 (N = 4) and GSE26712 (N = 9) datasets had significant p-values and consistent concordant with Duke Data. Despite the significant associations of gene expression and OS in the individual GSE datasets, in the GSE meta-analysis no genes were consistently concordant and significantly associated with survival. CONCLUSIONS: Evaluation of IL6R expression may be warranted based on higher expression in long-term survivors and association with improved survival in advanced HGSC. The other candidate genes may also be of worthy of further exploration to enhance immuno-oncology drug discovery.
Authors
Siamakpour-Reihani, S; Cobb, LP; Jiang, C; Zhang, D; Previs, RA; Owzar, K; Nixon, AB; Alvarez Secord, A
MLA Citation
Siamakpour-Reihani, Sharareh, et al. “Differential expression of immune related genes in high-grade ovarian serous carcinoma.Gynecol Oncol, vol. 156, no. 3, Mar. 2020, pp. 662–68. Pubmed, doi:10.1016/j.ygyno.2019.12.019.
URI
https://scholars.duke.edu/individual/pub1427231
PMID
31918995
Source
pubmed
Published In
Gynecol Oncol
Volume
156
Published Date
Start Page
662
End Page
668
DOI
10.1016/j.ygyno.2019.12.019

Statistical modeling of CALGB 80405 (Alliance) to identify influential factors in metastatic colorectal cancer (CRC) dependent on primary (1o) tumor side.

<jats:p> 3528 </jats:p><jats:p> Background: CALGB 80405 is a phase III clinical trial of FOLFOX and FOLFIRI w/ randomly assigned cetuximab or bevacizumab. Novel machine learning approaches to the study dataset provide valuable insights into CRC prognosis and management of CRC progression. Methods: Using a Monte Carlo Bayesian Generalized Linear Model analytical platform, we built an ensemble of models for overall survival (OS). We used 99 baseline and demographic variables, including 1904 patients w/ 1<jats:sup>o</jats:sup> side and 949 w/ KRAS wild-type status. Building an ensemble of predictive models reduces risk of overfitting, estimates model uncertainty and identifies key variables by model consensus as measured by ensemble frequency (freq). We fit gender and 1<jats:sup>o</jats:sup> side (L vs R) stratum-specific models to examine differences in drivers of disease in those strata. Results: 1<jats:sup>o</jats:sup> side (avg Cox hazard ratio = 0.89, R side reference), ECOG performance status (1.30, reference level 0), AST concentration (1.01), peripheral neutrophil percentage (1.01) and local primary and abdominal site of disease indicators (1.22; 1.26) were key variables predictive of OS ( &gt; 75% freq). In 1<jats:sup>o</jats:sup> side stratum-specific models, urine protein level (1.61), treatment intent (0.75, nonpalliative as reference) and hemoglobin concentration (0.85) were more associated w/ L side progression (freq &gt; 85% in L stratum model, &lt; 20% in R), while liver and lung sites of disease (2.3; 1.09) were more associated w/ R side progression (freq &gt; 65% in R stratum model, &lt; 20% in L). Predictors of 1<jats:sup>o</jats:sup> left-sidedness included age (avg log odds ratio = 0.02), hemoglobin (0.41), and abdominal (3.79) and liver (0.68) sites of disease. Modest differences in disease prognostic factors existed between genders: women more influenced by metastatic status, age, liver site of disease and creatinine level; men more influenced by urine protein level and prior diabetes. Conclusions: 1<jats:sup>o</jats:sup> side plays a central role in potentially explaining both variation in OS and differences in drivers of OS. Availability of these measures at baseline enables better sense of disease course at initiation of treatment. Support: U10CA180821, U10CA180882, Eli Lilly &amp; Co., Genentech, Pfizer Clinical trial information: NCT00265850. </jats:p>
Authors
Furchtgott, L; Swanson, D; Hayete, B; Khalil, I; Wuest, D; Rich, K; Nixon, AB; Niedzwiecki, D; Meyerhardt, JA; O'Reilly, EM; Ou, F-S; Lenz, H-J; Innocenti, F; Venook, AP
MLA Citation
Furchtgott, Leon, et al. “Statistical modeling of CALGB 80405 (Alliance) to identify influential factors in metastatic colorectal cancer (CRC) dependent on primary (1o) tumor side.Journal of Clinical Oncology, vol. 35, no. 15_suppl, American Society of Clinical Oncology (ASCO), 2017, pp. 3528–3528. Crossref, doi:10.1200/jco.2017.35.15_suppl.3528.
URI
https://scholars.duke.edu/individual/pub1438786
Source
crossref
Published In
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Volume
35
Published Date
Start Page
3528
End Page
3528
DOI
10.1200/jco.2017.35.15_suppl.3528

Longitudinal multiplex cytokine analysis for patients (pts) with metastatic renalcell carcinoma (mRCC) treated with ipilimumab/nivolumab (I plus N).

Authors
Zhang, T; Wu, Y; Agarwal, A; Starr, MD; Reyes-Martinez, M; Anand, M; Runyambo, D; Harrison, MR; Armstrong, AJ; George, DJ; Nixon, AB
MLA Citation
Zhang, Tian, et al. “Longitudinal multiplex cytokine analysis for patients (pts) with metastatic renalcell carcinoma (mRCC) treated with ipilimumab/nivolumab (I plus N).Journal of Clinical Oncology, vol. 38, no. 6, AMER SOC CLINICAL ONCOLOGY, 2020.
URI
https://scholars.duke.edu/individual/pub1441188
Source
wos
Published In
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Volume
38
Published Date

Angiogenesis plays a critical role in Group 3 medulloblastoma pathogenesis

Authors
Thompson, EM; Keir, S; Venkatraman, T; Lascola, C; Yeom, K; Nixon, A; Liu, Y; Picard, D; Remke, M; Ramaswamy, V; Taylor, M
MLA Citation
Thompson, Eric M., et al. “Angiogenesis plays a critical role in Group 3 medulloblastoma pathogenesis.” Journal of Neurosurgery, vol. 126, no. 4, AMER ASSOC NEUROLOGICAL SURGEONS, 2017, pp. A1436–A1436.
URI
https://scholars.duke.edu/individual/pub1438787
Source
wos
Published In
Journal of Neurosurgery
Volume
126
Published Date
Start Page
A1436
End Page
A1436