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:

Enzalutamide with androgen deprivation therapy in Japanese men with metastatic hormone-sensitive prostate cancer: A subgroup analysis of the phase III ARCHES study.

OBJECTIVE: To evaluate the efficacy and safety of enzalutamide plus androgen deprivation therapy in Japanese men with metastatic hormone-sensitive prostate cancer. METHODS: A post-hoc analysis of the Japanese subgroup in the phase III, randomized, multinational ARCHES study (NCT02677896) was carried out. Patients with metastatic hormone-sensitive prostate cancer were randomized to receive enzalutamide or a placebo, plus androgen deprivation therapy, stratified by disease volume and prior docetaxel therapy. The primary end-point was radiographic progression-free survival. Secondary end-points included time to prostate-specific antigen progression and overall survival. RESULTS: Of 1150 patients, 92 Japanese patients were randomized to enzalutamide (n = 36) or a placebo (n = 56), plus androgen deprivation therapy; none received prior docetaxel. Enzalutamide plus androgen deprivation therapy reduced the risk of radiographic progression or death in Japanese patients by 61% versus the placebo, similar to the overall population. Similar results were observed with secondary end-points, showing clinical benefit of enzalutamide plus androgen deprivation therapy in Japanese patients. Overall survival data were immature. Grade 3-4 adverse events were reported in 47% and 25% of the enzalutamide and placebo groups, respectively. Nasopharyngitis, hypertension and abnormal hepatic function were reported more frequently in Japanese patients versus the overall population. CONCLUSIONS: Enzalutamide plus androgen deprivation therapy has clinical benefit with a tolerable safety profile in Japanese men with metastatic hormone-sensitive prostate cancer, consistent with the overall population.
Authors
Iguchi, T; Kimura, G; Fukasawa, S; Suzuki, H; Uemura, H; Nishimura, K; Matsumoto, H; Yokomizo, A; Armstrong, AJ; Rosbrook, B; Sugg, J; Baron, B; Chen, L; Kunieda, F; Stenzl, A
MLA Citation
Iguchi, Taro, et al. “Enzalutamide with androgen deprivation therapy in Japanese men with metastatic hormone-sensitive prostate cancer: A subgroup analysis of the phase III ARCHES study.Int J Urol, vol. 28, no. 7, July 2021, pp. 765–73. Pubmed, doi:10.1111/iju.14568.
URI
https://scholars.duke.edu/individual/pub1482285
PMID
33955599
Source
pubmed
Published In
Int J Urol
Volume
28
Published Date
Start Page
765
End Page
773
DOI
10.1111/iju.14568

Correction: Angiokines Associated with Outcomes after Sunitinib or Everolimus Treatment in Patients with Non-Clear Cell Renal Cell Carcinoma.

Authors
Armstrong, AJ; Nixon, AB; Carmack, A; Yang, Q; Eisen, T; Stadler, WM; Jones, RJ; Garcia, JA; Vaishampayan, UN; Picus, J; Hawkins, RE; Hainsworth, JD; Kollmannsberger, CK; Logan, TF; Puzanov, I; Pickering, LM; Ryan, CW; Protheroe, A; George, DJ; Halabi, S
MLA Citation
Armstrong, Andrew J., et al. “Correction: Angiokines Associated with Outcomes after Sunitinib or Everolimus Treatment in Patients with Non-Clear Cell Renal Cell Carcinoma.Clin Cancer Res, vol. 27, no. 12, June 2021, p. 3503. Pubmed, doi:10.1158/1078-0432.CCR-21-1636.
URI
https://scholars.duke.edu/individual/pub1486354
PMID
34117029
Source
pubmed
Published In
Clinical Cancer Research
Volume
27
Published Date
Start Page
3503
DOI
10.1158/1078-0432.CCR-21-1636

Enzalutamide versus bicalutamide in patients with nonmetastatic castration-resistant prostate cancer: a prespecified subgroup analysis of the STRIVE trial.

BACKGROUND: In the phase 2, randomized, double-blind STRIVE trial, enzalutamide significantly reduced the risk of prostate cancer progression or death versus bicalutamide in patients with metastatic castration-resistant prostate cancer (mCRPC) and nonmetastatic CRPC (nmCRPC). The objective of this protocol-specified subgroup analysis of STRIVE was to investigate the benefit of enzalutamide versus bicalutamide specifically in patients with nmCRPC. METHODS: Patients (N = 139) were stratified by disease stage and randomized to enzalutamide 160 mg/day plus androgen deprivation therapy (ADT; n = 70) or bicalutamide 50 mg/day plus ADT (n = 69). RESULTS: Baseline characteristics of patients with nmCRPC were comparable between groups. At a median of 17 months follow-up, enzalutamide reduced the risk of progression or death by 76% versus bicalutamide in patients with nmCRPC (hazard ratio [HR], 0.24; 95% CI 0.14-0.42). Enzalutamide reduced risk of prostate-specific antigen progression by 82% versus bicalutamide in patients with nmCRPC (HR, 0.18; 95% CI 0.10-0.34). The most frequently reported adverse events by patients receiving enzalutamide were fatigue (36.2%), hot flush (20.3%), decreased appetite (17.4%), dizziness (17.4%), and nausea (17.4%). CONCLUSIONS: This STRIVE subgroup analysis of patients with nmCRPC illustrates the benefit of enzalutamide in reducing the risk of progression or death versus bicalutamide in patients with nmCRPC. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT01664923.
Authors
Penson, DF; Armstrong, AJ; Concepcion, RS; Agarwal, N; Olsson, CA; Karsh, LI; Dunshee, CJ; Duggan, W; Shen, Q; Sugg, J; Haas, GP; Higano, CS
MLA Citation
Penson, David F., et al. “Enzalutamide versus bicalutamide in patients with nonmetastatic castration-resistant prostate cancer: a prespecified subgroup analysis of the STRIVE trial.Prostate Cancer Prostatic Dis, Oct. 2021. Pubmed, doi:10.1038/s41391-021-00465-7.
URI
https://scholars.duke.edu/individual/pub1498518
PMID
34621011
Source
pubmed
Published In
Prostate Cancer Prostatic Dis
Published Date
DOI
10.1038/s41391-021-00465-7

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