Andrew Armstrong

Overview:

1. Predictors of sensitivity and clinical efficacy of therapies in advanced prostate cancer
2. Novel designs of clinical trials and pharmacodynamic/translational studies in prostate, kidney, bladder cancer
3. Pre-operative models for drug development of novel agents in human testing in prostate cancer
4. Novel therapies and drug development for prostate, renal, bladder, and testicular cancer
5. Design of rational combination therapies in men with metastatic hormone-refractory prostate cancer
6. PI3 kinase/mTOR inhibition in prostate cancer: mechanisms of sensitivity and resistance
7. Developing prognostic models for progression and survival in metastatic prostate cancer
8. Examining surrogate markers of mortality in metastatic prostate cancer
9. Clear cell and non-clear cell renal cell carcinoma: natural history, sensitivity to novel agents including mTOR and VEGF inhibition

Positions:

Professor of Medicine

Medicine, Medical Oncology
School of Medicine

Associate Professor in Pharmacology and Cancer Biology

Pharmacology & Cancer Biology
School of Medicine

Professor in Surgery

Surgery, Urology
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

B.S.E. 1996

Duke University

M.D. 2000

University of Virginia School of Medicine

M.Sc. 2008

Johns Hopkins University

Internship/Residency, General Internal Medicine

University of Pennsylvania School of Medicine

Fellowship, Division Of Oncology/Hematology

Johns Hopkins University School of Medicine

Grants:

Propel Protocol ID: D081SC00001

Administered By
Duke Cancer Institute
Role
Principal Investigator
Start Date
End Date

ProSTAR: CPI-1205

Administered By
Duke Cancer Institute
Role
Principal Investigator
Start Date
End Date

VISION PSMA-617-01

Administered By
Duke Cancer Institute
Role
Principal Investigator
Start Date
End Date

A Phase 2 Study of Nivolumab in combination with either Rucaparib, docetaxel, or enzalutamide in men with Castration-resistant metastaic prostate cancer (CheckMate 9KD: CHECKpoint pathway and nivoluMA

Administered By
Duke Cancer Institute
Role
Principal Investigator
Start Date
End Date

MK7123

Administered By
Duke Cancer Institute
Role
Principal Investigator
Start Date
End Date

Publications:

Association Between New Unconfirmed Bone Lesions and Outcomes in Men With Metastatic Castration-Resistant Prostate Cancer Treated With Enzalutamide: Secondary Analysis of the PREVAIL and AFFIRM Randomized Clinical Trials.

Importance: For men with metastatic castration-resistant prostate cancer (mCRPC) whose condition is responding to enzalutamide, new unconfirmed bone lesions detected at posttreatment scinitigraphy may reflect an osteoblastic reaction that represents healing, known as pseudoprogression, which can lead to premature discontinuation of therapy. Objective: To determine the association between new unconfirmed lesions detected on a follow-up bone scintigram (bone scan) and outcomes in enzalutamide-treated men with mCRPC. Design, Setting, and Participants: This post hoc, retrospective secondary analysis of 1672 enzalutamide-treated men from 2 phase 3, randomized mCRPC studies (PREVAIL and AFFIRM) before or after treatment with docetaxel was conducted from April 12, 2018, to July 25, 2019. Participants were men from the enzalutamide groups of the 2 studies with a decrease in prostate-specific antigen level at any time or with stable disease or soft-tissue disease responding to treatment based onradiologic findings. Intervention: Enzalutamide, 160 mg once daily. Main Outcomes and Measures: The clinical significance of new lesions detected on the first (early) or second (late) posttreatment bone scan, without an unfavorable change in prostate-specific antigen level or soft-tissue progression, was investigated. Associations of new unconfirmed lesions with radiographic progression-free survival, overall survival, decrease in prostate-specific antigen level, objective response in soft tissue, and quality of life were evaluated. Results: Among the 643 men (median age, 72 years [range, 43-93 years]) in PREVAIL, early and late unconfirmed lesions were observed in 177 men (27.5%) with stable disease or disease responding to enzalutamide. Among the 404 men (median age, 70 years [range, 41-88 years]) in AFFIRM, early and late unconfirmed lesions were observed in 73 men (18.1%) with stable disease or disease responding to enzalutamide. In PREVAIL, men with new unconfirmed lesions had median radiographic progression-free survival (hazard ratio [HR], 1.37 [95% CI, 0.81-2.30]; P = .23) and median overall survival (HR, 1.25 [95% CI, 0.85-1.83]) in the chemotherapy-naive setting similar to men those of men without such new lesions. In AFFIRM, the median overall survival (HR, 1.94 [95% CI, 1.10-3.44]) was reduced among men with unconfirmed bone lesions, but the median radiographic progression-free survival was not reduced (HR, 1.21 [95% CI, 0.83-1.75]; P = .32). Quality of life over time was similar regardless of the presence of new unconfirmed lesions detected on a follow-up bone scan in either setting. Conclusions and Relevance: These results suggest that new unconfirmed lesions detected on follow-up bone scans may represent pseudoprogression in men with mCRPC and are indicative of a favorable treatment response to enzalutamide. The detection of new unconfirmed bone lesions in men with mCRPC that responded to treatment with enzalutamide after docetaxel appears to be associated with worse overall survival and may represent true progression, thus highlighting the need for improved functional bone metastasis imaging. Trial Registration: ClinicalTrials.gov identifier: NCT01212991 and NCT00974311.
Authors
Armstrong, AJ; Al-Adhami, M; Lin, P; Parli, T; Sugg, J; Steinberg, J; Tombal, B; Sternberg, CN; de Bono, J; Scher, HI; Beer, TM
URI
https://scholars.duke.edu/individual/pub1423099
PMID
31830211
Source
pubmed
Published In
Jama Oncol
Published Date
DOI
10.1001/jamaoncol.2019.4636

Targeting cellular heterogeneity with CXCR2 blockade for the treatment of therapy-resistant prostate cancer.

Hormonal therapy targeting androgen receptor (AR) is initially effective to treat prostate cancer (PCa), but it eventually fails. It has been hypothesized that cellular heterogeneity of PCa, consisting of AR+ luminal tumor cells and AR- neuroendocrine (NE) tumor cells, may contribute to therapy failure. Here, we describe the successful purification of NE cells from primary fresh human prostate adenocarcinoma based on the cell surface receptor C-X-C motif chemokine receptor 2 (CXCR2). Functional studies revealed CXCR2 to be a driver of the NE phenotype, including loss of AR expression, lineage plasticity, and resistance to hormonal therapy. CXCR2-driven NE cells were critical for the tumor microenvironment by providing a survival niche for the AR+ luminal cells. We demonstrate that the combination of CXCR2 inhibition and AR targeting is an effective treatment strategy in mouse xenograft models. Such a strategy has the potential to overcome therapy resistance caused by tumor cell heterogeneity.
Authors
Li, Y; He, Y; Butler, W; Xu, L; Chang, Y; Lei, K; Zhang, H; Zhou, Y; Gao, AC; Zhang, Q; Taylor, DG; Cheng, D; Farber-Katz, S; Karam, R; Landrith, T; Li, B; Wu, S; Hsuan, V; Yang, Q; Hu, H; Chen, X; Flowers, M; McCall, SJ; Lee, JK; Smith, BA; Park, JW; Goldstein, AS; Witte, ON; Wang, Q; Rettig, MB; Armstrong, AJ; Cheng, Q; Huang, J
MLA Citation
Li, Yanjing, et al. “Targeting cellular heterogeneity with CXCR2 blockade for the treatment of therapy-resistant prostate cancer..” Sci Transl Med, vol. 11, no. 521, Dec. 2019. Pubmed, doi:10.1126/scitranslmed.aax0428.
URI
https://scholars.duke.edu/individual/pub1423084
PMID
31801883
Source
pubmed
Published In
Sci Transl Med
Volume
11
Published Date
DOI
10.1126/scitranslmed.aax0428

Concordance between PD-L1 assays for metastatic renal cell carcinoma (mRCC) and metastatic urothelial carcinoma (mUC).

Authors
Zhu, J; Labriola, M; Cheris, S; Liu, X; Perkinson, K; Su, Z; McCall, S; Huang, J; Gupta, R; Armstrong, AJ; George, DJ; Zhang, T
MLA Citation
Zhu, Jason, et al. “Concordance between PD-L1 assays for metastatic renal cell carcinoma (mRCC) and metastatic urothelial carcinoma (mUC)..” Journal of Clinical Oncology, vol. 37, no. 7_suppl, American Society of Clinical Oncology (ASCO), 2019, pp. 577–577. Crossref, doi:10.1200/jco.2019.37.7_suppl.577.
URI
https://scholars.duke.edu/individual/pub1416785
Source
crossref
Published In
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Volume
37
Published Date
Start Page
577
End Page
577
DOI
10.1200/jco.2019.37.7_suppl.577

Discordant and heterogeneous clinically relevant genomic alterations in circulating tumor cells vs plasma DNA from men with metastatic castration resistant prostate cancer.

Circulating tumor cell (CTC) and cell-free (cf) DNA-based genomic alterations are increasingly being used for clinical decision-making in oncology. However, the concordance and discordance between paired CTC and cfDNA genomic profiles remain largely unknown. We performed comparative genomic hybridization (CGH) on CTCs and cfDNA, and low-pass whole genome sequencing (lpWGS) on cfDNA to characterize genomic alterations (CNA) and tumor content in two independent prospective studies of 93 men with mCRPC treated with enzalutamide/abiraterone, or radium-223. Comprehensive analysis of 69 patient CTCs and 72 cfDNA samples from 93 men with mCRPC, including 64 paired samples, identified common concordant gains in FOXA1, AR, and MYC, and losses in BRCA1, PTEN, and RB1 between CTCs and cfDNA. Concordant PTEN loss and discordant BRCA2 gain were associated with significantly worse outcomes in Epic AR-V7 negative men with mCRPC treated with abiraterone/enzalutamide. We identified and externally validated CTC-specific genomic alternations that were discordant in paired cfDNA, even in samples with high tumor content. These CTC/cfDNA-discordant regions included key genomic regulators of lineage plasticity, osteomimicry, and cellular differentiation, including MYCN gain in CTCs (31%) that was rarely detected in cfDNA. CTC MYCN gain was associated with poor clinical outcomes in AR-V7 negative men and small cell transformation. In conclusion, we demonstrated concordance of multiple genomic alterations across CTC and cfDNA platforms; however, some genomic alterations displayed substantial discordance between CTC DNA and cfDNA despite the use of identical copy number analysis methods, suggesting tumor heterogeneity and divergent evolution associated with poor clinical outcomes.
Authors
Gupta, S; Hovelson, DH; Kemeny, G; Halabi, S; Foo, W-C; Anand, M; Somarelli, JA; Tomlins, SA; Antonarakis, ES; Luo, J; Dittamore, RV; George, DJ; Rothwell, C; Nanus, DM; Armstrong, AJ; Gregory, SG
URI
https://scholars.duke.edu/individual/pub1421556
PMID
31705765
Source
pubmed
Published In
Genes Chromosomes Cancer
Published Date
DOI
10.1002/gcc.22824

Pembrolizumab in men with heavily treated metastatic castration-resistant prostate cancer (mCRPC).

Authors
Tucker, MD; Zhu, J; Berry, WR; Ramalingam, S; Zhang, T; Harrison, MR; Wu, Y; Healy, P; George, DJ; Armstrong, AJ
MLA Citation
Tucker, Matthew D., et al. “Pembrolizumab in men with heavily treated metastatic castration-resistant prostate cancer (mCRPC)..” Journal of Clinical Oncology, vol. 37, no. 7_suppl, American Society of Clinical Oncology (ASCO), 2019, pp. 172–172. Crossref, doi:10.1200/jco.2019.37.7_suppl.172.
URI
https://scholars.duke.edu/individual/pub1416786
Source
crossref
Published In
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Volume
37
Published Date
Start Page
172
End Page
172
DOI
10.1200/jco.2019.37.7_suppl.172