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

Professor in Surgery

Surgery, Urology
School of Medicine

Professor in Pharmacology and Cancer Biology

Pharmacology & Cancer Biology
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:

Study title: A Randomized, Double-blind, Placebo-controlled, Multicenter Phase III Study of Olaparib Plus Abiraterone Relative to Placebo Plus Abiraterone as First-line Therapy in Men with Metastatic Castration-resistant Prostate Cancer

Administered By
Duke Cancer Institute
Awarded By
AstraZeneca AB
Role
Principal Investigator
Start Date
End Date

ProSTAR: A Phase 1b/2 Study of CPI-1205, a Small Molecule Inhibitor of EZH2, Combined with Enzalutamide or Abiraterone/Prednisone in Patients with Metastatic Castration Resistant Prostate Cancer

Administered By
Duke Cancer Institute
Awarded By
Constellation Pharmaceuticals
Role
Principal Investigator
Start Date
End Date

VISION: An International, Prospective, Open-Label, Multicenter, Randomized Phase 3 Study of 177lu-Psma-617 in the Treatment of Patients with Progressive PSMA-Positive Metastatic Castration-Resistant Prostate Cancer (mCRPC)

Administered By
Duke Cancer Institute
Awarded By
Endocyte, Inc.
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
Awarded By
Bristol-Myers Squibb Company
Role
Principal Investigator
Start Date
End Date

A Phase II Study of Navarixin (MK-7123) in Combination with Pembrolizumab (MK-3475) in Participants with Selected Advanced/Metastatic Solid Tumors

Administered By
Duke Cancer Institute
Awarded By
Merck Sharp & Dohme
Role
Principal Investigator
Start Date
End Date

Publications:

Impact of enzalutamide on patient-reported fatigue in patients with prostate cancer: data from the pivotal clinical trials.

BACKGROUND: Fatigue is a multifactorial symptom commonly reported by patients with prostate cancer as a result of disease and treatment. This study assesses the impact enzalutamide has on patient-reported fatigue ("fatigue") by using patient-reported outcomes from four pivotal, placebo-controlled trials of enzalutamide (ARCHES (NCT02677896), PROSPER (NCT02003924), PREVAIL (NCT01212991), and AFFIRM (NCT00974311)). METHODS: Fatigue was assessed in the individual studies using the Functional Assessment of Cancer Therapy-Prostate item GP1 at baseline, weeks 13 or 17, and every 12 weeks until disease progression. Longitudinal changes were assessed using mean scores and mixed-model repeated measures. RESULTS: The fatigue rates at baseline were higher in patients with later-stage disease (metastatic and/or castration-resistant prostate cancer (CRPC)) and among patients who had already received prior treatment lines; rates ranged between 58% in PROSPER (nonmetastatic CRPC) and 86% in AFFIRM (post-docetaxel metastatic CRPC). Irrespective of disease state, initiation of enzalutamide or placebo resulted in an early increase of fatigue (by weeks 13 or 17), with fatigue levels stabilizing thereafter. At last assessment, ≥55% of patients reported fatigue improvement or stabilization in all trials compared to baseline. More patients reported fatigue worsening by ≥1 or ≥2 units with enzalutamide plus androgen deprivation therapy (ADT) than with placebo plus ADT in ARCHES, PROSPER, and PREVAIL, but the between-group difference was <10% in all trials. CONCLUSIONS: The levels of fatigue were greater in mCRPC and lower in earlier states of disease. In all trials, patients reported a small increase in fatigue for the first 13-17 weeks after starting enzalutamide or placebo, with slightly greater fatigue with enzalutamide in all studies except AFFIRM, but fatigue stabilized or improved thereafter. This suggests a role for clinical management of fatigue to help patients cope early in treatment.
Authors
Tombal, BF; Freedland, SJ; Armstrong, AJ; Beer, TM; Stenzl, A; Sternberg, CN; Hussain, M; Ganguli, A; Ramaswamy, K; Bhadauria, H; Ivanescu, C; Turnbull, J; Holmstrom, S; Saad, F
MLA Citation
Tombal, Bertrand F., et al. “Impact of enzalutamide on patient-reported fatigue in patients with prostate cancer: data from the pivotal clinical trials.Prostate Cancer Prostatic Dis, Sept. 2021. Pubmed, doi:10.1038/s41391-021-00447-9.
URI
https://scholars.duke.edu/individual/pub1497522
PMID
34518652
Source
pubmed
Published In
Prostate Cancer Prostatic Dis
Published Date
DOI
10.1038/s41391-021-00447-9

Prospective Evaluation of Clinical Outcomes Using a Multiplex Liquid Biopsy Targeting Diverse Resistance Mechanisms in Metastatic Prostate Cancer.

PURPOSE: Nearly all men with prostate cancer treated with androgen receptor (AR) signaling inhibitors (ARSIs) develop resistance via diverse mechanisms including constitutive activation of the AR pathway, driven by AR genomic structural alterations, expression of AR splice variants (AR-Vs), or loss of AR dependence and lineage plasticity termed neuroendocrine prostate cancer. Understanding these de novo acquired ARSI resistance mechanisms is critical for optimizing therapy. MATERIALS AND METHODS: A novel liquid biopsy technology was used to collect mRNA from circulating tumor cells (CTCs) to measure expression of AR-Vs, AR targets, and neuroendocrine prostate cancer markers. An institutional review board-approved prospective cohort (N = 99) was used to identify patterns of gene expression. Two prospective multicenter phase II clinical trials of ARSIs for men with castration-resistant prostate cancer (ClinicalTrials.gov: NCT01942837 [enzalutamide, N = 21] and NCT02025010 [abiraterone, N = 27]) were used to further validate these findings. RESULTS: Hierarchical clustering of CTC transcripts identified two distinct clusters. Cluster 2 (C2) exhibited increased expression of AR-regulated genes and was associated with worse overall survival (median 8.6 v 22.4 months; P < .01; hazard ratio [HR] = 3.45 [1.9 to 6.14]). In multivariable analysis, C2 was prognostic independent of other clinicopathologic variables. AR-V status was not significant when accounting for C2. Upon further validation in pooled multicenter phase II trials, C2 was associated with worse overall survival (15.2 months v not reached; P < .01; HR = 8.43 [2.74 to 25.92]), prostate-specific antigen progression-free survival (3.6 v 12 months; P < .01; HR = 4.64 [1.53 to 14.11]), and radiographic progression-free survival (2.7 v 40.6 months; P < .01; HR = 4.64 [1.82 to 17.41]). CONCLUSION: We demonstrate that a transcriptional profile detectable in CTCs obtained from liquid biopsies can serve as an independent prognostic marker beyond AR-V7 in patients with metastatic prostate cancer and can be used to identify the emergence of multiple ARSI resistance mechanisms. This is currently being investigated in additional prospective trials.
Authors
Sperger, JM; Emamekhoo, H; McKay, RR; Stahlfeld, CN; Singh, A; Chen, XE; Kwak, L; Gilsdorf, CS; Wolfe, SK; Wei, XX; Silver, R; Zhang, Z; Morris, MJ; Bubley, G; Feng, FY; Scher, HI; Rathkopf, D; Dehm, SM; Choueiri, TK; Halabi, S; Armstrong, AJ; Wyatt, AW; Taplin, M-E; Zhao, SG; Lang, JM
MLA Citation
Sperger, Jamie M., et al. “Prospective Evaluation of Clinical Outcomes Using a Multiplex Liquid Biopsy Targeting Diverse Resistance Mechanisms in Metastatic Prostate Cancer.J Clin Oncol, vol. 39, no. 26, Sept. 2021, pp. 2926–37. Pubmed, doi:10.1200/JCO.21.00169.
URI
https://scholars.duke.edu/individual/pub1487553
PMID
34197212
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
39
Published Date
Start Page
2926
End Page
2937
DOI
10.1200/JCO.21.00169

A Phase Ib Study of Atezolizumab with Radium-223 Dichloride in Men with Metastatic Castration-Resistant Prostate Cancer.

<h4>Purpose</h4>Men with metastatic castration-resistant prostate cancer (mCRPC) have limited treatment options after progressing on hormonal therapy and chemotherapy. Here, we evaluate the safety and efficacy of atezolizumab (anti-PD-L1) + radium-223 dichloride (radium-223) in men with mCRPC.<h4>Patients and methods</h4>This phase Ib study evaluated atezolizumab + radium-223 in men with mCRPC and bone and lymph node and/or visceral metastases that progressed after androgen pathway inhibitor treatment. Following safety assessment of concurrent dosing, 45 men were randomized 1:1:1 to concurrent or one of two staggered dosing schedules with either agent introduced one cycle before the other. This was followed by a safety-efficacy expansion cohort (randomized 1:1:1). The primary endpoints were safety and objective response rate (ORR) by RECIST 1.1. Secondary endpoints included radiographic progression-free survival (rPFS), PSA responses, and overall survival (OS).<h4>Results</h4>As of October 4, 2019, 44 of 45 men were evaluable. All 44 had ≥1 all-cause adverse event (AE); 23 (52.3%) had a grade 3/4 AE. Fifteen (34.1%) grade 3/4 and 3 (6.8%) grade 5 AEs were related to atezolizumab; none were related to radium-223. Confirmed ORR was 6.8% [95% confidence interval (CI), 1.4-18.7], median rPFS was 3.0 months (95% CI, 2.8-4.6), median PSA progression was 3.0 months (95% CI, 2.8-3.3), and median OS was 16.3 months (95% CI, 10.9-22.3).<h4>Conclusions</h4>This phase Ib study demonstrated that atezolizumab + radium-223, regardless of administration schedule, had greater toxicity than either drug alone, with no clear evidence of additional clinical benefit for patients with mCRPC and bone and lymph node and/or visceral metastases.
Authors
Fong, L; Morris, MJ; Sartor, O; Higano, CS; Pagliaro, L; Alva, A; Appleman, LJ; Tan, W; Vaishampayan, U; Porcu, R; Tayama, D; Kadel, EE; Yuen, KC; Datye, A; Armstrong, AJ; Petrylak, DP
MLA Citation
Fong, Lawrence, et al. “A Phase Ib Study of Atezolizumab with Radium-223 Dichloride in Men with Metastatic Castration-Resistant Prostate Cancer.Clinical Cancer Research : An Official Journal of the American Association for Cancer Research, vol. 27, no. 17, Sept. 2021, pp. 4746–56. Epmc, doi:10.1158/1078-0432.ccr-21-0063.
URI
https://scholars.duke.edu/individual/pub1484975
PMID
34108181
Source
epmc
Published In
Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
Volume
27
Published Date
Start Page
4746
End Page
4756
DOI
10.1158/1078-0432.ccr-21-0063

579MO CheckMate 9KD cohort A2 final analysis: Nivolumab (NIVO) + rucaparib for chemotherapy (CT)-naïve metastatic castration-resistant prostate cancer (mCRPC)

Authors
Petrylak, DP; Perez-Gracia, JL; Lacombe, L; Bastos, DA; Mahammedi, H; Kwan, EM; Zschäbitz, S; Armstrong, AJ; Pachynski, RK; Goh, JC; Burotto, M; Gravis, G; McCune, SL; Vázquez Limón, JC; Retz, M; Saad, F; Amin, NP; Li, J; Unsal-Kacmaz, K; Fizazi, K
MLA Citation
Petrylak, D. P., et al. “579MO CheckMate 9KD cohort A2 final analysis: Nivolumab (NIVO) + rucaparib for chemotherapy (CT)-naïve metastatic castration-resistant prostate cancer (mCRPC).” Annals of Oncology, vol. 32, Elsevier BV, 2021, pp. S629–30. Crossref, doi:10.1016/j.annonc.2021.08.1092.
URI
https://scholars.duke.edu/individual/pub1498324
Source
crossref
Published In
Annals of Oncology
Volume
32
Published Date
Start Page
S629
End Page
S630
DOI
10.1016/j.annonc.2021.08.1092

Analysis of immune subtypes across the epithelial-mesenchymal plasticity spectrum.

Epithelial-mesenchymal plasticity plays a critical role in many solid tumor types as a mediator of metastatic dissemination and treatment resistance. In addition, there is also a growing appreciation that the epithelial/mesenchymal status of a tumor plays a role in immune evasion and immune suppression. A deeper understanding of the immunological features of different tumor types has been facilitated by the availability of large gene expression datasets and the development of methods to deconvolute bulk RNA-Seq data. These resources have generated powerful new ways of characterizing tumors, including classification of immune subtypes based on differential expression of immunological genes. In the present work, we combine scoring algorithms to quantify epithelial-mesenchymal plasticity with immune subtype analysis to understand the relationship between epithelial plasticity and immune subtype across cancers. We find heterogeneity of epithelial-mesenchymal transition (EMT) status both within and between cancer types, with greater heterogeneity in the expression of EMT-related factors than of MET-related factors. We also find that specific immune subtypes have associated EMT scores and differential expression of immune checkpoint markers.
Authors
Chakraborty, P; Chen, EL; McMullen, I; Armstrong, AJ; Kumar Jolly, M; Somarelli, JA
MLA Citation
Chakraborty, Priyanka, et al. “Analysis of immune subtypes across the epithelial-mesenchymal plasticity spectrum.Comput Struct Biotechnol J, vol. 19, 2021, pp. 3842–51. Pubmed, doi:10.1016/j.csbj.2021.06.023.
URI
https://scholars.duke.edu/individual/pub1489075
PMID
34306571
Source
pubmed
Published In
Computational and Structural Biotechnology Journal
Volume
19
Published Date
Start Page
3842
End Page
3851
DOI
10.1016/j.csbj.2021.06.023