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:

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:

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

ASSET: Alternative schedule sunitinib in metastatic renal cell carcinoma (RCC)—Cardiopulmonary exercise testing (CPET).

<jats:p> 300 </jats:p><jats:p> Background: Sunitinib (SUN) is a vascular endothelial growth factor (VEGF) tyrosine kinase inhibitor (TKI) approved for treatment of advanced RCC and high risk RCC after nephrectomy. Evidence suggests that a 2 week (wk) on, 1 wk off schedule (2/1) of SUN administration may be more tolerable than the standard 4 wk on, 2 wk off schedule (4/2). We investigated changes in cardiopulmonary function and related parameters over time in RCC patients treated with both schedules of SUN. Methods: Patients starting SUN for RCC, with KPS ≥80 and normal organ and marrow function, were enrolled and randomized 1:1 to schedule 4/2 or 2/1. Subjects were required to be able to walk and jog on a treadmill and to complete an acceptable CPET at baseline (BL). Primary endpoint was change in peak oxygen uptake (VO<jats:sub>2</jats:sub>peak) on both schedules at 12 wk from BL. Key secondary endpoints were change from BL to 12 wk in: left ventricular ejection fraction (LVEF), upper and lower body strength (1-RM), functional measures (chair stand, timed up-and-go [TUG], 6-minute walk test [6MWT], quality of life (QOL; FACT-Fatigue, FKSI-19), anxiety and depression (HADS) and exercise behavior (Godin Leisure Score). ANCOVA models controlling for baseline values were used to analyze the primary and secondary endpoints. Results: Between 11/20/2017 and 6/24/2019, 9 out of a planned 30 patients consented to participate at Duke. Two patients declined to participate and 7 patients were enrolled on study: 4 on Arm A and 3 on Arm B. All 7 patients completed the 12 wk study. Median age, BMI, and VO<jats:sub>2</jats:sub>peak were 65 yrs, 30.5 kg/m<jats:sup>2</jats:sup>, and 19.2 ml kg<jats:sup>−1</jats:sup> min<jats:sup>−1</jats:sup>. We observed no difference in the primary endpoint of VO<jats:sub>2</jats:sub>peak between arms (p=0.84). We report BL to 12 wk change scores for all patients starting SUN (Table). In addition, mean change scores (SE) for QOL by FACIT-Fatigue and FKSI-19 were -2.88 (1.5) and 1.2 [9.8]; anxiety and depression by HADS 1.14 (1.3); and physical activity 1.14 (1.7). Conclusions: We observed non-significant declines in most measures of physical fitness and function during the first 12 wk of treatment with SUN. To our knowledge, this is the first reported study of these parameters in patients with RCC. Given that a VEGF TKI, alone and with an immune checkpoint inhibitor, remains a standard of care for metastatic ccRCC, studies should be undertaken to examine whether exercise training can prevent declines in physical fitness and function. Clinical trial information: NCT03109015 . [Table: see text] </jats:p>
Authors
Harrison, MR; Bartlett, D; Zhang, T; Armstrong, AJ; Coburn, A; Coyne, B; Anand, M; Oyekunle, T; Wu, Y; Khouri, M; George, DJ
MLA Citation
Harrison, Michael Roger, et al. “ASSET: Alternative schedule sunitinib in metastatic renal cell carcinoma (RCC)—Cardiopulmonary exercise testing (CPET).Journal of Clinical Oncology, vol. 39, no. 6_suppl, American Society of Clinical Oncology (ASCO), 2021, pp. 300–300. Crossref, doi:10.1200/jco.2021.39.6_suppl.300.
URI
https://scholars.duke.edu/individual/pub1480290
Source
crossref
Published In
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Volume
39
Published Date
Start Page
300
End Page
300
DOI
10.1200/jco.2021.39.6_suppl.300

A prospective trial of abiraterone acetate plus prednisone in Black and White men with metastatic castrate-resistant prostate cancer.

BACKGROUND: Retrospective analyses of randomized trials suggest that Black men with metastatic castration-resistant prostate cancer (mCRPC) have longer survival than White men. The authors conducted a prospective study of abiraterone acetate plus prednisone to explore outcomes by race. METHODS: This race-stratified, multicenter study estimated radiographic progression-free survival (rPFS) in Black and White men with mCRPC. Secondary end points included prostate-specific antigen (PSA) kinetics, overall survival (OS), and safety. Exploratory analysis included genome-wide genotyping to identify single nucleotide polymorphisms associated with progression in a model incorporating genetic ancestry. One hundred patients self-identified as White (n = 50) or Black (n = 50) were enrolled. Eligibility criteria were modified to facilitate the enrollment of individual Black patients. RESULTS: The median rPFS for Black and White patients was 16.6 and 16.8 months, respectively; their times to PSA progression (TTP) were 16.6 and 11.5 months, respectively; and their OS was 35.9 and 35.7 months, respectively. Estimated rates of PSA decline by ≥50% in Black and White patients were 74% and 66%, respectively; and PSA declines to <0.2 ng/mL were 26% and 10%, respectively. Rates of grade 3 and 4 hypertension, hypokalemia, and hyperglycemia were higher in Black men. CONCLUSIONS: Multicenter prospective studies by race are feasible in men with mCRPC but require less restrictive eligibility. Despite higher comorbidity rates, Black patients demonstrated rPFS and OS similar to those of White patients and trended toward greater TTP and PSA declines, consistent with retrospective reports. Importantly, Black men may have higher side-effect rates than White men. This exploratory genome-wide analysis of TTP identified a possible candidate marker of ancestry-dependent treatment outcomes.
Authors
George, DJ; Halabi, S; Heath, EI; Sartor, AO; Sonpavde, GP; Das, D; Bitting, RL; Berry, W; Healy, P; Anand, M; Winters, C; Riggan, C; Kephart, J; Wilder, R; Shobe, K; Rasmussen, J; Milowsky, MI; Fleming, MT; Bearden, J; Goodman, M; Zhang, T; Harrison, MR; McNamara, M; Zhang, D; LaCroix, BL; Kittles, RA; Patierno, BM; Sibley, AB; Patierno, SR; Owzar, K; Hyslop, T; Freedman, JA; Armstrong, AJ
MLA Citation
URI
https://scholars.duke.edu/individual/pub1481831
PMID
33951180
Source
pubmed
Published In
Cancer
Published Date
DOI
10.1002/cncr.33589

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