Xiaofei Wang

Overview:

Design and Analysis of Clinical Trials
Nonparametric and Semiparametric Methods
Survival Analysis
Causal Inference
Methods for Diagnostic and Predictive Medicine
Biomarker Discovery and Validation
Health Outcomes Research

Positions:

Professor of Biostatistics & Bioinformatics

Biostatistics & Bioinformatics
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

Ph.D. 2003

University of North Carolina - Chapel Hill

Graduate Research Assistant, Computer Sciences

University of North Carolina - Chapel Hill

Graduate Research Assistant, Biostatistics

University of North Carolina - Chapel Hill

Grants:

Translational meta-analysis for elderly lung cancer patients

Administered By
Biostatistics & Bioinformatics
Awarded By
National Institutes of Health
Role
Principal Investigator
Start Date
End Date

Cancer and Leukemia Group B Statistical Center

Administered By
Duke Cancer Institute
Awarded By
National Institutes of Health
Role
Statistician
Start Date
End Date

Semiparametric ROC Curve Regression for Cancer Screening Studies

Administered By
Biostatistics & Bioinformatics
Awarded By
National Institutes of Health
Role
Principal Investigator
Start Date
End Date

Methods for Discovery and Analysis of Dynamic Treatment Regimes

Administered By
Biostatistics & Bioinformatics
Awarded By
University of North Carolina - Chapel Hill
Role
Investigator
Start Date
End Date

Administrative Core

Administered By
Biostatistics & Bioinformatics
Awarded By
University of North Carolina - Chapel Hill
Role
Co Investigator
Start Date
End Date

Publications:

Sintilimab, stereotactic body radiotherapy and granulocyte-macrophage colony stimulating factor as second-line therapy for advanced non-small cell lung cancer: safety run-in results of a multicenter, single-arm, phase II trial.

OBJECTIVES: The SWORD trial is the first multicenter, single arm, phase II study assessing the safety and efficacy of a PD-1 inhibitor (Sintilimab), stereotactic body radiotherapy (SBRT) and granulocyte-macrophage colony stimulating factor (GM-CSF) in advanced non-small cell lung cancer (NSCLC) without sensitizing driver mutations. A safety run-in phase was conducted to determine the tolerability of the experimental treatment. MATERIALS AND METHODS: Twenty metastatic NSCLC patients who failed first-line chemotherapy were enrolled, and they received SBRT (8 Gy × 3) to one lesion, followed by Sintilimab (200 mg d1, every 3 weeks, until disease progression, unacceptable toxicity, or up to 35 cycles) and GM-CSF (125 μg/m2 d1-d14, cycle 1) within 2 weeks after SBRT. In addition, blood and tissue samples were serially collected for translational research. RESULTS: Median age of the patients was 61 and all of them had more than 5 lesions at baseline. The sites of SBRT included lung (n = 11), mediastinal lymph node (n = 5), liver (n = 1), abdominal lymph node (n = 1), pleural nodule (n = 1) and vertebra (n = 1). No patients had dose-limiting toxicities (DLTs) and 18 patients experienced treatment-related adverse event (TRAE). The most common TRAEs were fatigue (50%), fever (30%), and ostealgia (20%), and they all were grade 1. Only 2 grade 3 TRAEs were observed, including elevation of liver enzymes in one and transient acute heart failure in another. No grade 4 or 5 AE was observed. CONCLUSION: Sintilimab, SBRT and GM-CSF for advanced NSCLC is safe with manageable TRAEs and the trial continues to recruit participants. Trial registration ClinicalTrials.gov, NCT04106180. Registered 26 September 2019, SBRT in Combination With Sintilimab and GM-CSF for the Treatment of Advanced NSCLC-Tabular View-ClinicalTrials.gov.
Authors
Ni, J; Zhou, Y; Wu, L; Ai, X; Dong, X; Chu, Q; Han, C; Wang, X; Zhu, Z
URI
https://scholars.duke.edu/individual/pub1497238
PMID
34526044
Source
pubmed
Published In
Radiation Oncology
Volume
16
Published Date
Start Page
177
DOI
10.1186/s13014-021-01905-3

Alliance Foundation Trial 09: A Randomized, Multicenter, Phase 2 Trial Evaluating Two Sequences of Pembrolizumab and Standard Platinum-Based Chemotherapy in Patients With Metastatic NSCLC.

Introduction: The sequence of chemotherapy and pembrolizumab may affect antitumor immune response and efficacy of immunotherapy. Methods: This multicenter, randomized, phase 2 trial was designed to evaluate the efficacy of two sequences of chemotherapy and pembrolizumab in patients with stage 4 NSCLC. Both arms were considered investigational, and the study used a "pick a winner" design. The primary end point was objective response rate by independent radiologic review after eight cycles (24 wk). Patients were randomized 1:1 to arm A (chemotherapy for four cycles followed by pembrolizumab for four cycles) or arm B (pembrolizumab for four cycles followed by chemotherapy for four cycles). Patients in both arms without disease progression after the initial eight cycles continued pembrolizumab until disease progression, unacceptable toxicity, or a maximum of 2 years. Results: From March 2016 to July 2018, a total of 90 eligible patients were randomized (43 patients to arm A and 47 patients to arm B). The objective response rate at 24 weeks in arms A and B was 39.5 % (95 % confidence interval [CI]: 24.9%-54.1 %) and 40.4 % (95 % CI: 26.4%-54.5 %), respectively (p = 0.93). The progression-free survival in arms A and B was as follows: hazard ratio of B versus A equals to 1.06, 95 % CI: 0.68-1.66, p value equals to 0.84, and median progression-free survival of 5.8 months and 4 months, respectively. The overall survival was as follows: hazard ratio of B versus A equals to 1.04, 95 % CI: 0.63-1.74, p value equals to 0.85, and median overall survival of 15.5 months and 14 months, respectively. Conclusions: Additional evaluation of either sequence in a phase 3 trial is not warranted.
Authors
Hensing, TA; Wang, X; Stinchcombe, TE; Gao, J; Knopp, MV; Watson, M; Dudek, AZ; Graziano, SL; Patel, JD; Faller, BA; Dragnev, KH; Kozono, D; Vokes, EE
MLA Citation
Hensing, Thomas A., et al. “Alliance Foundation Trial 09: A Randomized, Multicenter, Phase 2 Trial Evaluating Two Sequences of Pembrolizumab and Standard Platinum-Based Chemotherapy in Patients With Metastatic NSCLC.Jto Clin Res Rep, vol. 2, no. 8, Aug. 2021, p. 100208. Pubmed, doi:10.1016/j.jtocrr.2021.100208.
URI
https://scholars.duke.edu/individual/pub1494315
PMID
34590049
Source
pubmed
Published In
Jto Clinical and Research Reports
Volume
2
Published Date
Start Page
100208
DOI
10.1016/j.jtocrr.2021.100208

Clinical Trials with Biologic Primary Endpoints in Immuno-oncology: Concepts and Usage.

Clinical trials that have a pharmacokinetic or a pharmacodynamic immunologic mechanism of action-based primary outcome could substantially improve the validity and efficiency of early development of immuno-oncology agents. Here, we outline different trial design options in this area, review examples from the literature and their unique immunologic aspects, and highlight how these trials have been underutilized. We illustrate how new technologies and translationally focused approaches can be successfully used to develop different classes of immunotherapeutic agents.
Authors
Isaacs, J; Tan, AC; Hanks, BA; Wang, X; Owzar, K; Herndon, JE; Antonia, SJ; Piantadosi, S; Khasraw, M
MLA Citation
Isaacs, James, et al. “Clinical Trials with Biologic Primary Endpoints in Immuno-oncology: Concepts and Usage.Clin Cancer Res, July 2021. Pubmed, doi:10.1158/1078-0432.CCR-21-1593.
URI
https://scholars.duke.edu/individual/pub1489704
PMID
34312214
Source
pubmed
Published In
Clinical Cancer Research
Published Date
DOI
10.1158/1078-0432.CCR-21-1593

Nomogram Predicting Overall Survival Benefit of Stereotactic Ablative Radiotherapy for Early-Stage Non-Small Cell Lung Cancer.

OBJECTIVES: To develop and validate a nomogram that predicts overall survival (OS) for patients with early-stage non-small cell lung cancer (NSCLC) treated with stereotactic ablative radiotherapy (SABR) vs. observation. MATERIALS AND METHODS: Adults with biopsy-proven T1-T2N0 NCSLC treated with SABR (30-70 Gy in 1-10 fractions with biologically effective dose ≥100 Gy10) or observation between 2004 and 2015 in the National Cancer Database (NCDB) were identified. Propensity score was used to match SABR and observation cohorts on prognostic demographic and clinicopathologic factors identified by logistic regression. Using backward selection, a multivariable Cox proportional hazard was identified predicting 2- and 5-year OS via a nomogram. Model prediction accuracy was assessed by time-dependent receiver operating characteristic (ROC) curves and integrated area under the ROC curve (AUC) analysis. RESULTS: A total of 22,073 adults met inclusion criteria and 4418 matched pairs (total n = 8836) were identified for nomogram development. The factors most strongly associated with improved OS on multivariable analysis included younger age (HR 0.82 by decade, P < .001), female sex (HR 0.81, P < .001), lower comorbidity index (HR 0.65 for 0 vs. ≥3, P < .001), smaller tumor size (HR 0.60 for ≤3 cm vs. 5.1-7 cm, P < .001), adenocarcinoma histology (P < .001), and receipt of SABR (P < .001). Interaction between SABR and histology was significantly associated with OS (P = .017). Relative to adenocarcinoma, patients with squamous cell carcinoma who were observed (HR 1.44, 95% CI 1.33-1.56) or treated with SABR (HR 1.24, 95% CI 1.14-1.35) had significantly worse OS. The nomogram demonstrated fair accuracy for predicting OS, with an integrated time-dependent AUC of 0.694 over the entire follow-up period. CONCLUSION: This nomogram estimates OS at 2 and 5 years based on whether medically inoperable early-stage NSCLC patients receive SABR or elect for observation. Incorporation of other variables not captured within the NCDB may improve the model accuracy.
Authors
Jacobs, CD; Mehta, K; Gao, J; Wang, X; Salama, JK; Kelsey, CR; Torok, JA
MLA Citation
Jacobs, Corbin D., et al. “Nomogram Predicting Overall Survival Benefit of Stereotactic Ablative Radiotherapy for Early-Stage Non-Small Cell Lung Cancer.Clin Lung Cancer, June 2021. Pubmed, doi:10.1016/j.cllc.2021.06.008.
URI
https://scholars.duke.edu/individual/pub1489730
PMID
34301453
Source
pubmed
Published In
Clin Lung Cancer
Published Date
DOI
10.1016/j.cllc.2021.06.008

Time-To-Event Data: An Overview and Analysis Considerations.

In oncology, overall survival and progression-free survival are common time-to-event end points used to measure treatment efficacy. Analyses of this type of data rely on a complex statistical framework and the analysis results are only valid when the data meet certain assumptions. This article provides an overview of time-to-event data, the basic mechanics of common analysis methods, and issues often encountered when analyzing such data. Our goal is to provide clinicians and other lung cancer researchers with the knowledge to choose the appropriate time-to-event analysis methods and to interpret the outcomes of such analyses appropriately. We strongly encourage investigators to seek out statisticians with expertise in survival analysis when embarking on studies that include time-to-event data to ensure that their data are collected and analyzed using the appropriate methods.
Authors
Le-Rademacher, J; Wang, X
MLA Citation
Le-Rademacher, Jennifer, and Xiaofei Wang. “Time-To-Event Data: An Overview and Analysis Considerations.J Thorac Oncol, vol. 16, no. 7, July 2021, pp. 1067–74. Pubmed, doi:10.1016/j.jtho.2021.04.004.
URI
https://scholars.duke.edu/individual/pub1480576
PMID
33887465
Source
pubmed
Published In
J Thorac Oncol
Volume
16
Published Date
Start Page
1067
End Page
1074
DOI
10.1016/j.jtho.2021.04.004