Susan Halabi

Overview:

Design and analysis of clinical trials, statistical analysis of biomarker and high dimensional data, development and validation of prognostic and predictive models.

Positions:

Professor of Biostatistics and Bioinformatics

Biostatistics & Bioinformatics
School of Medicine

Chief, Division of Biostatistics

Biostatistics & Bioinformatics
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

Ph.D. 1994

University of Texas Health Sciences Center, Houston

Grants:

PCRP Clinical Consortium: Duke University Clinical Research Site

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

Developing and Validating Prognostic Models of Clinical Outcomes In Men With Castration Resistant Prostate Cancer

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

Surrogate Endpoints of Overall Survival in Men with Metastatic Hormone Sensitive Prostate Cancer

Administered By
Biostatistics & Bioinformatics
Awarded By
Prostate Cancer Foundation
Role
Principal Investigator
Start Date
End Date

Precision Medicine in Platinum-treated Lethal Bladder Cancer

Administered By
Biostatistics & Bioinformatics
Awarded By
Memorial Sloan Kettering Cancer Center
Role
Principal Investigator
Start Date
End Date

Serum Androgens and Survival in CRPC

Administered By
Duke Cancer Institute
Awarded By
University of California - San Francisco
Role
Principal Investigator
Start Date
End Date

Publications:

Identification of prognostic and predictive biomarkers of overall survival (OS) and progression-free survival (PFS) in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) treated with docetaxel, prednisone (DP) +/- bevacizumab (B)

<jats:p> 154 </jats:p><jats:p> Background: CALGB 90401 was a phase III trial of 1050 pts with mCRPC comparing DP+B versus DP alone. While this trial did not show an improvement in OS in the overall population, there were improved PSA response, objective responses and delays in progression suggesting that subsets of men may derive benefit from this combination The purpose of this analysis was to identify and validate plasma angiokines (PAs) that are prognostic or predictive of OS and PFS benefit from bevacizumab in men with mCRPC. Methods: Baseline EDTA plasma samples from 679 consenting pts were analyzed using an optimized multiplex ELISA platform for 25 PAs related to tumor growth, angiogenesis, and inflammation. The data were randomly split into training (n = 462) and testing (n = 217) sets. The proportional hazards model was utilized to test for the prognostic and predictive importance of the PAs in predicting OS and PFS, with and without adjustment for clinical risk score. Analyses were adjusted for multiplicity using false discovery rate (FDR). Results: For the prognostic analysis, 14 PAs (angiopoeitin-2, BMP9, Chromogranin A, HER3, HGF, ICAM-1, IL6, OPN, PIGF, TIMP, TSP2, VEGFA, VEGFR1, and VEGF-R3) were prognostic of OS and 8 PAs (angiopoietin-2, HER3, ICAM-1, IL6, OPN, TIMP, VEGFA and VEGF-R3) were prognostic of PFS in the training set (FDR &lt; 0.05). None of the PAs were statistically significant for OS or PFS when adjusting by the clinical risk score, suggesting that angiokine levels associate with clinical prognostic factors. OPN was predictive of OS in the training set but no other PAs were found to be predictive of PFS improvement with DP+B. Using the testing set, we were unable to validate that OPN is predictive of OS/PFS or any of the PAs are predictive biomarkers of the OS or PFS benefits of DP+B over DP alone in men with mCRPC. Conclusions: While PAs are prognostic for OS and PFS in univariate analysis, we were unable to validate the results in the testing set. Furthermore, we did not identify any PAs that are predictive of benefit from the addition of bevacizumab to docetaxel/prednisone with ADT in this setting. Nevertheless, these remain worthy of further evaluation as potential therapeutic targets. </jats:p>
Authors
Halabi, S; Yang, Q; Starr, MD; Brady, JC; Armstrong, AJ; George, DJ; Kelly, WK; Beltran, H; Morris, MJ; Nixon, AB
MLA Citation
Halabi, Susan, et al. “Identification of prognostic and predictive biomarkers of overall survival (OS) and progression-free survival (PFS) in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) treated with docetaxel, prednisone (DP) +/- bevacizumab (B) in CALGB 90401 (Alliance).Journal of Clinical Oncology, vol. 39, no. 6_suppl, American Society of Clinical Oncology (ASCO), 2021, pp. 154–154. Crossref, doi:10.1200/jco.2021.39.6_suppl.154.
URI
https://scholars.duke.edu/individual/pub1480287
Source
crossref
Published In
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Volume
39
Published Date
Start Page
154
End Page
154
DOI
10.1200/jco.2021.39.6_suppl.154

Development and validation of circulating tumor cell (Epic Sciences) enumeration as a prognostic biomarker in men with metastatic castration-resistant prostate cancer.

<jats:p> 157 </jats:p><jats:p> Background: We evaluated the prognostic significance of circulating tumor cell (CTC) number as determined on the Epic Sciences platform in men with metastatic castration resistant prostate cancer (mCRPC) treated with an androgen receptor signaling inhibitor (ARSI). Methods: A pre-treatment blood sample was collected from men with progressing mCRPC starting either abiraterone or enzalutamide as a 1st, 2nd or 3rd line systemic therapy at Memorial Sloan Kettering Cancer Center (Discovery cohort, N=175) or as a 1st and 2nd line therapy as part of the multi-center PROPHECY trial (NCT02269982) (Validation cohort, N=107). Enumeration was performed on the Epic Sciences platform and associated with overall survival (OS) in the Discovery cohort, and progression-free survival (PFS) and OS in the Validation cohort. Matched blood samples from the Validation cohort were to CTC counts measured on the CellSearch Circulating Tumor Cell kit. Results: In the MSKCC Discovery cohort, CTC count was a statistically significant prognostic factor of OS as a dichotomous (&lt; 3 CTCs/mL versus ≥ 3 CTCs/mL; HR = 1.8, (1.3-3.0, 95% CI)) and as a continuous variable when adjusting for line of therapy, presence of visceral metastases, PSA, lactate-dehydrogenase, and alkaline-phosphatase. The findings were validated in an independent dataset (PROPHECY trial) - (HR (95% CI) = 1.8, (1.1-3.0) for OS and 1.7 (1.1-2.9), for PFS). A strong correlation was observed between CTC counts determined in matched samples on the CellSearch and Epic platforms (r = 0.84). Conclusions: The findings validate the prognostic significance of pretreatment CTC number determined on the Epic Sciences platform for predicting OS in men with progressing mCRPC starting an ARSI. </jats:p>
Authors
Scher, HI; Armstrong, AJ; Schonhoft, JD; Gill, A; Zhao, J; Barnett, E; Carbone, E; Lu, J; Antonarakis, ES; Luo, J; Tagawa, ST; Yang, Q; George, DJ; Szmulewitz, RZ; Danila, DC; Wenstrup, R; Gonen, M; Halabi, S
MLA Citation
Scher, Howard I., et al. “Development and validation of circulating tumor cell (Epic Sciences) enumeration as a prognostic biomarker in men with metastatic castration-resistant prostate cancer.Journal of Clinical Oncology, vol. 39, no. 6_suppl, American Society of Clinical Oncology (ASCO), 2021, pp. 157–157. Crossref, doi:10.1200/jco.2021.39.6_suppl.157.
URI
https://scholars.duke.edu/individual/pub1480295
Source
crossref
Published In
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Volume
39
Published Date
Start Page
157
End Page
157
DOI
10.1200/jco.2021.39.6_suppl.157

Efficacy of the PD-L1 inhibitor avelumab in neuroendocrine or aggressive variant prostate cancer: Results from a phase II, single-arm study.

<jats:p> 89 </jats:p><jats:p> Background: Men with metastatic neuroendocrine/small cell and aggressive variant prostate cancer (NEPC/AVPC) have poor outcomes despite platinum and taxane chemotherapy. These tumors share common features with small cell lung cancer, including higher tumor mutational burden and genomic alterations, and thus may be responsive to immunotherapy. Methods: We conducted a single arm, 2-stage phase II investigator-sponsored trial, (PICK-NEPC, NCT03179410) with the PD-L1 inhibitor avelumab in patients with NEPC/AVPC. NEPC/AVPC was defined either by histologic criteria (neuroendocrine or small cell features) by central pathology review or by aggressive variant clinical criteria (prior progression on abiraterone or enzalutamide with liver metastasis, bulky radiographic progression and low PSA, or high serum LDH). Prior chemotherapy or hormonal therapy was allowed. Avelumab 10 mg/kg IV every 2 weeks was administered until progression or unacceptable toxicity with ongoing ADT. The primary endpoint was overall response rate (ORR) defined by modified PCWG3 and iRECIST criteria. Results: We consented 19 men with AVPC/NEPC, and 15 initiated treatment with avelumab. The median age was 71 (range 51-85), and 27% had neuroendocrine or small cell histology, while 73% met AVPC clinical criteria with adenocarcinoma histology. Men had received a median of two prior systemic therapies (range 1-3) including carboplatin (27%), docetaxel (73%), enzalutamide (67%), and abiraterone (47%). Median PSA was 54 ng/mL (range 0-393) and 73% had liver metastasis. The ORR by iRECIST was 6.7% (95% CI 0-32%) with 1 CR, 0 PRs, 3 (20%) with stable disease, and 11 (73%) with progressive disease. The patient with a CR had NEPC with a CNS metastasis that was found to be MSI-high/TMB-high due to a somatic MSH2 alteration; he finished 12 months of avelumab and maintains a durable CR and undetectable PSA 6 months after completing all therapy including ADT. Median radiographic progression free survival was 1.8 months (95% CI 1.6-2.0 mo) and median time on therapy was 56 days (range 28-356). Median overall survival was 7.4 mo (85% CI 2.8-12.5 mo). Two grade 3 adverse events (abdominal pain due to hepatic disease progression versus immune hepatitis and pericarditis), and one grade 4 (immune hepatitis) adverse event were attributed to avelumab with no grade 5 adverse events. Grade 1 or 2 infusion-related reactions were experienced by 9 (60%). Conclusions: PD-L1 inhibition with avelumab demonstrated limited clinical efficacy in men with metastatic NEPC/AVPC other than in those with MSI-high disease. Further research is needed into mechanisms of immune evasion in NEPC/AVPC to develop novel immunotherapies. Clinical trial information: NCT03179410. </jats:p>
Authors
Brown, LC; Halabi, S; Humeniuk, MS; Wu, Y; Oyekunle, T; Huang, J; Anand, M; Davies, C; Zhang, T; Harrison, MR; George, DJ; Armstrong, AJ
MLA Citation
Brown, Landon Carter, et al. “Efficacy of the PD-L1 inhibitor avelumab in neuroendocrine or aggressive variant prostate cancer: Results from a phase II, single-arm study.Journal of Clinical Oncology, vol. 39, no. 6_suppl, American Society of Clinical Oncology (ASCO), 2021, pp. 89–89. Crossref, doi:10.1200/jco.2021.39.6_suppl.89.
URI
https://scholars.duke.edu/individual/pub1480300
Source
crossref
Published In
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Volume
39
Published Date
Start Page
89
End Page
89
DOI
10.1200/jco.2021.39.6_suppl.89

Randomized Phase III Trial of Gemcitabine and Cisplatin With Bevacizumab or Placebo in Patients With Advanced Urothelial Carcinoma: Results of CALGB 90601 (Alliance).

PURPOSE: The combination of gemcitabine and cisplatin (GC) is a standard therapy for metastatic urothelial carcinoma. Based on data that angiogenesis plays a role in urothelial carcinoma growth and progression, a randomized placebo-controlled trial was performed with the primary objective of testing whether patients treated with GC and bevacizumab (GCB) have superior overall survival (OS) than patients treated with GC and placebo (GCP). PATIENTS AND METHODS: Between July 2009 and December 2014, 506 patients with metastatic urothelial carcinoma without prior chemotherapy for metastatic disease and no neoadjuvant or adjuvant chemotherapy within 12 months were randomly assigned to receive either GCB or GCP. The primary end point was OS, with secondary end points of progression-free survival, objective response, and toxicity. RESULTS: With a median follow-up of 76.3 months among alive patients, the median OS was 14.5 months for patients treated with GCB and 14.3 months for patients treated with GCP (hazard ratio for death = 0.87; 95% CI, 0.72 to 1.05; two-sided stratified log-rank P = .14). The median progression-free survival was 8.0 months for GCB and 6.7 months for GCP (hazard ratio = 0.77; 95% CI, 0.63 to 0.95; P = .016). The proportion of patients with grade 3 or greater adverse events did not differ significantly between both arms, although increased bevacizumab-related toxicities such as hypertension and proteinuria occurred in the bevacizumab-treated arm. CONCLUSION: The addition of bevacizumab to GC did not result in improved OS. The observed median OS of about 14 months is consistent with prior phase III trials of cisplatin-based chemotherapy.
Authors
Rosenberg, JE; Ballman, KA; Halabi, S; Atherton, PJ; Mortazavi, A; Sweeney, C; Stadler, WM; Teply, BA; Picus, J; Tagawa, ST; Katragadda, S; Vaena, D; Misleh, J; Hoimes, C; Plimack, ER; Flaig, TW; Dreicer, R; Bajorin, D; Hahn, O; Small, EJ; Morris, MJ
MLA Citation
URI
https://scholars.duke.edu/individual/pub1482201
PMID
33989025
Source
pubmed
Published In
Journal of Clinical Oncology
Published Date
Start Page
JCO2100286
DOI
10.1200/JCO.21.00286

Severe-COVID-19 and mortality among patients (pts) with prostate cancer (PCa) receiving androgen deprivation therapy (ADT).

<jats:p> 39 </jats:p><jats:p> Background: The presence of progressing cancer, male sex and advanced age have been shown to increase the severity of coronavirus disease 2019 (COVID-19). Given that the androgen regulated gene TMPRSS2 has been implicated in SARS-CoV-2 viral entry, we hypothesized that ADT may improve COVID-19 outcomes. This analysis evaluated clinical outcomes of pts with PCa with concurrent SARS-CoV-2 infection and investigated the impact of ADT on occurrence of severe-COVID-19 and mortality. Methods: Data was obtained via the COVID-19 and Cancer Consortium (CCC19), a multicenter registry including &gt;120 cancer centers with de-identified data from pts with COVID-19 and cancer. Men with confirmed SARS-CoV-2 infection and a primary diagnosis of prostate cancer were included: data cutoff of July 31, 2020. The primary endpoint was the development of severe-COVID-19 (death, ICU admission, or mechanical ventilation) among pts on ADT vs. those not on ADT at time of COVID-19 infection. Secondary endpoints included 30-day mortality based on ADT use. Mortality and development of severe-COVID-19 were assessed in Pts grouped by therapy: 1st generation androgen receptor inhibitor (ARI-1), 2nd generation ARI (darolutamide, enzalutamide, apalutamide, ARI-2), abiraterone/prednisone, and chemotherapy. Propensity score matching was utilized. Logistic regression was utilized to adjust for age, ECOG PS, comorbidities, and race. Results: 589 pts were included; median follow-up was 42 days (IQR 25-90) and 62% (363/589) were hospitalized. Severe-COVID-19 developed in 28% of pts and the all-cause 30-day mortality rate was 19%. There was no significant difference in the development of severe-COVID-19 or 30-day mortality between Pts on ADT vs not on ADT, whether using descriptive statistics with the entire population or using the propensity score matched population (Table). Among the descriptive population, the numerical rates of severe-COVID-19 and mortality were lowest in Pts receiving ARI-2, but sample size was low. Conclusions: The overall 30-day mortality rate and percentage developing severe-COVID-19 were high. There was no statistical difference in the development of severe-COVID-19 or mortality based on receipt of ADT; however, this analysis is limited by the retrospective nature and small N after propensity-matching. [Table: see text] </jats:p>
Authors
Tucker, MD; Schmidt, AL; Hsu, C-Y; Shyr, Y; Armstrong, AJ; Bakouny, Z; Chapman, CH; Dawsey, S; Gartrell, BA; Halabi, S; Joshi, M; Khaki, AR; Menon, H; Puc, M; Sharifi, N; Shaya, J; Wulff-Burchfield, EM; Zhang, T; Gupta, S; McKay, RR
MLA Citation
Tucker, Matthew D., et al. “Severe-COVID-19 and mortality among patients (pts) with prostate cancer (PCa) receiving androgen deprivation therapy (ADT).Journal of Clinical Oncology, vol. 39, no. 6_suppl, American Society of Clinical Oncology (ASCO), 2021, pp. 39–39. Crossref, doi:10.1200/jco.2021.39.6_suppl.39.
URI
https://scholars.duke.edu/individual/pub1480330
Source
crossref
Published In
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Volume
39
Published Date
Start Page
39
End Page
39
DOI
10.1200/jco.2021.39.6_suppl.39

Research Areas:

Adenocarcinoma
Adenocarcinoma, Clear Cell
African Americans
Age Factors
Aged, 80 and over
Alkaline Phosphatase
Alleles
Arab countries
Area Under Curve
Biological Markers
Biomarkers, Pharmacological
Breast Neoplasms
Cancer Vaccines
Carcinoma
Carcinoma, Renal Cell
Case-Control Studies
Chemoprevention
Chemotherapy
Chi-Square Distribution
Clinical Trials, Phase II as Topic
Clinical trials
Cohort Studies
Computer Simulation
Confidence Intervals
Construction Materials
Contraceptives, Oral
DNA Damage
DNA Primers
DNA Repair
DNA, Neoplasm
Data Interpretation, Statistical
Decision Making
Decision Support Techniques
Diagnostic Imaging
Disease Progression
Disease-Free Survival
Drug Design
Dust
Efficiency, Organizational
Endpoint Determination
Equipment Design
Factor Analysis, Statistical
Family relationships
Gels
Gene Expression
Genes, Immunoglobulin
Genetic Predisposition to Disease
Genetics, Medical
Genotype
Germany
Graft vs Host Disease
HIV Infections
Hispanic Americans
Individualized Medicine
Kaplan-Meier Estimate
Ketoconazole
Lasso
Logistic Models
Lymphokines
Mining
Models, Biological
Models, Statistical
Models, Theoretical
Molecular Sequence Data
Multiprotein Complexes
Multivariate Analysis
Mutation
Neoplasms, Hormone-Dependent
Nomograms
Odds Ratio
Outcome Assessment (Health Care)
Ovarian Neoplasms
Personalized medicine
Population
Population Surveillance
Precision Medicine
Predictive Value of Tests
Pregnancy
Probability
Prognosis
Proportional Hazards Models
Prospective Studies
ROC Curve
Randomized Controlled Trials as Topic
Receptors, Progesterone
Registries
Reproducibility of Results
Research Design
Residence Characteristics
Retrospective Studies
Ribosomal Protein S6 Kinases
Risk
Risk Assessment
Risk Factors
Sample Size
Selective Estrogen Receptor Modulators
Sensitivity and Specificity
Statistics as Topic
Survival
Survival Analysis
Survival Rate
Tamoxifen
Translocation, Genetic
Treatment Failure
Treatment Outcome
Tumor Markers, Biological
United States
Urologic Neoplasms
Validation Studies as Topic
Vascular Endothelial Growth Factors