Richard Riedel

Overview:

Novel therapies for soft tissue and bone sarcomas

Positions:

Associate Professor of Medicine

Medicine, Medical Oncology
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

M.D. 2000

Thomas Jefferson University

Resident in Medicine, Medicine

Duke University

Fellow in Hematology-Oncology, Medicine

Duke University

Fellow in Hematology-Oncology, Medicine

Duke University

Grants:

An International, Multicenter, Open-label, Randomized, Phase 3 Study of BLU-285 vs Regorafenib in Patients with Locally Advanced Unresectable or Metastatic Gastrointestinal Stromal Tumor (GIST)

Administered By
Duke Cancer Institute
Awarded By
Blueprint Medicines Corporation
Role
Principal Investigator
Start Date
End Date

Dissecting Mechanisms of Metastasis Through Comparative Systems Genetics

Administered By
Radiation Oncology
Awarded By
National Institutes of Health
Role
Investigator
Start Date
End Date

A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Trial of Nirogacestat Versus Placebo in Adult Patients With Progressing Desmoid Tumors/Aggressive Fibromatosis (DT/AF)

Administered By
Duke Cancer Institute
Awarded By
SpringWorks Therapeutics
Role
Principal Investigator
Start Date
End Date

A Phase 3, Interventional, Randomized, Multicenter, Open-Label Study of DCC-2618 vs Sunitinib in Patients with Advanced Gastrointestinal Stromal Tumors after Treatment with Imatinib

Administered By
Duke Cancer Institute
Awarded By
Deciphera Pharmaceuticals, LLC
Role
Principal Investigator
Start Date
End Date

A Phase 3, Randomized, Double-blind, Placebo-controlled Study to Determine the Efficacy and Safety of MB305 in Unresectable Locally-advanced or Metastatic NY-ESO-1+ Synovial Sarcoma Subjects Following First-line Systemic Anti-cancer Therapy

Administered By
Duke Cancer Institute
Awarded By
Immune Design Corp.
Role
Principal Investigator
Start Date
End Date

Publications:

A Randomized, Double-Blind, Placebo-Controlled, Phase II Study of Regorafenib Versus Placebo in Advanced/Metastatic, Treatment-Refractory Liposarcoma: Results from the SARC024 Study.

TRIAL INFORMATION: ClinicalTrials.gov Identifier: NCT02048371 Sponsors: SARC, with support from Bayer HealthCare Pharmaceuticals (Berlin, Germany) Principal Investigator: Richard F. Riedel IRB Approved: Yes LESSONS LEARNED: The results from the liposarcoma cohort of SARC024 confirm previously published data and do not support the routine use of regorafenib in this patient population. Continued exploration of novel therapies, including combination approaches, is warranted for a patient population in whom limited treatment options exist. BACKGROUND: Regorafenib is a multitargeted kinase inhibitor with a kinase profile overlapping, but distinct from, pazopanib, an agent approved for recurrent and metastatic non-gastrointestinal stromal tumor (GIST), non-adipocytic soft tissue sarcoma. We conducted a randomized, phase II study of regorafenib versus placebo in refractory liposarcoma patients. METHODS: Patients with advanced or metastatic, treatment-refractory liposarcoma were randomized 1:1 to receive regorafenib 160 mg or placebo once daily (3 weeks on, 1 week off). Patients with well-differentiated liposarcoma only were excluded. Crossover for placebo was allowed upon progression. The primary endpoint was progression-free survival (PFS), according to RECIST version 1.1. RESULTS: Forty-eight subjects with liposarcoma (34 dedifferentiated, 12 myxoid/round cell, 2 pleomorphic) were enrolled. Median PFS was 1.87 (95% confidence interval [CI], 0.92-3.67) months for regorafenib versus 2.07 (95% CI, 1.64-3.44) months for placebo; stratified hazard ratio [HR], 0.85 (95% CI, 0.46, 1.58), p = .62. No responses were seen on regorafenib. One PR was observed on placebo. Median overall survival was 6.46 (95% CI, 4.16-23.48) months for regorafenib and 4.89 (95% CI, 3.02-9.77) months for placebo, stratified HR, 0.66 (95% CI, 0.31-1.40), p = .28). Treatment-related adverse events were similar to the known safety profile of regorafenib. CONCLUSION: Regorafenib did not appear to improve PFS in treatment-refractory liposarcoma. No new significant safety signals were observed.
Authors
Riedel, RF; Ballman, KV; Lu, Y; Attia, S; Loggers, ET; Ganjoo, KN; Livingston, MB; Chow, W; Wright, J; Ward, JH; Rushing, D; Okuno, SH; Reed, DR; Liebner, DA; Keedy, VL; Mascarenhas, L; Davis, LE; Ryan, C; Reinke, DK; Maki, RG
URI
https://scholars.duke.edu/individual/pub1452546
PMID
32701199
Source
pubmed
Published In
Oncologist
Published Date
DOI
10.1634/theoncologist.2020-0679

Academic-Practice Partnership for Caregiver Training and Support: The Duke Elder Family/Caregiver Training (DEFT) Center.

BACKGROUND After a hospital stay, many older adults rely on their caregivers for assistance at home. Empirical evidence demonstrates that caregiver support programs in hospital-to-home transitions are associated with favorable caregiver and patient outcomes. We tested the feasibility of implementing the Duke Elder Family/Caregiver Training (DEFT) program in an academic medical center.METHODS: We recruited adult caregivers of homebound patients who were aged 55 years or older from Duke University Hospital in Durham, North Carolina. Caregivers attended a face-to-face caregiver training and received two telephone checks after hospital discharge with DEFT services ending at 14 days of hospital discharge. We used a one-item survey to measure overall DEFT satisfaction. We also monitored 30-day readmissions of patients whose caregivers completed the DEFT program.RESULTS: The DEFT Center received 104 consult orders in six months. Of these, 61 agreed to participate but nine caregivers were unable to schedule the DEFT training and three decided to eventually withdraw from participation. Forty-nine caregivers received the DEFT training, 12 of whom were ineligible to continue because of change in patients' disposition plan. Of the remaining 37 caregivers, 15 completed the full program and reported high satisfaction; one patient was readmitted within 30 days of discharge.LIMITATIONS: The DEFT implementation was based on academic-medical partnership and relied on electronic medical records for consult and documentation. Replicability and generalizability of findings are limited to settings with similar capabilities and resources.CONCLUSION: The implementation of a caregiver training and support program in an academic medical center was feasible and was associated with favorable preliminary outcomes.
Authors
Hendrix, CC; Matters, D; Griffin, T; Batchelder, H; Kramer, P; Prewitt, JR; Matters, L; Lytle, K; Yang, Y; Park, H; Riedel, RF; Choi, JY; McConnell, E
MLA Citation
Hendrix, Cristina C., et al. “Academic-Practice Partnership for Caregiver Training and Support: The Duke Elder Family/Caregiver Training (DEFT) Center.N C Med J, vol. 81, no. 4, July 2020, pp. 221–27. Pubmed, doi:10.18043/ncm.81.4.221.
URI
https://scholars.duke.edu/individual/pub1451123
PMID
32641453
Source
pubmed
Published In
North Carolina Medical Journal
Volume
81
Published Date
Start Page
221
End Page
227
DOI
10.18043/ncm.81.4.221

Co-occurrence of targetable mutations in Non-small cell lung cancer (NSCLC) patients harboring MAP2K1 mutations.

BACKGROUND:MAP2K1 mutations are rare in non-small cell lung cancer (NSCLC) and considered to be mutually exclusive from known driver mutations. Activation of the MEK1-cascade is considered pivotal in resistance to targeted therapy approaches, and MAP2K1 K57 N mutation could be linked to resistance in preclinical models. We set out this study to detect MAP2K1 mutations and potentially targetable co-mutations using a molecular multiplex approach. METHODS:Between 2012 and 2018, we routinely analyzed 14.512 NSCLC patients with two next-generation sequencing (NGS) panels. In a subset of patients, fluorescence in-situ hybridization was performed to detect rearrangements or amplifications. We assessed clinical parameters and co-occurring mutations and compared treatment outcomes of different forms of systemic therapy. RESULTS:We identified 66 (0.5%) patients with MAP2K1 mutations. Both adenocarcinoma (n = 62) and squamous cell carcinoma (n = 4) histology. The presence of the mutations was linked to smoking, and transversions were more common than transitions. K57 N was the most frequent MAP2K1 mutation (n = 25). Additional mutations were found in 57 patients (86.4%). Mutations of TP53 were detected in 33 patients, followed by KEAP1 mutations in 28.1%. 24 patients (36.4%) had either MAP2K1-only or a co-occurring aberration considered targetable, including EGFR mutations, a BRAF V600E mutation and ROS1 rearrangements. Outcome analyses revealed a trend toward benefit from pemetrexed treatment. CONCLUSION:Our analysis shows that MAP2K1-mutated NSCLC patients might frequently present with potentially targetable aberrations. Their role in providing resistance in these subtypes and the possible therapeutic opportunities justify further analyses of this rare NSCLC subgroup.
Authors
Scheffler, M; Holzem, A; Kron, A; Nogova, L; Ihle, MA; von Levetzow, C; Fassunke, J; Wömpner, C; Bitter, E; Koleczko, S; Abdulla, DSY; Michels, S; Fischer, R; Riedel, R; Weber, J-P; Westphal, T; Gerigk, U; Kern, J; Kaminsky, B; Randerath, W; Kambartel, K-O; Merkelbach-Bruse, S; Büttner, R; Wolf, J
MLA Citation
Scheffler, Matthias, et al. “Co-occurrence of targetable mutations in Non-small cell lung cancer (NSCLC) patients harboring MAP2K1 mutations.Lung Cancer (Amsterdam, Netherlands), vol. 144, June 2020, pp. 40–48. Epmc, doi:10.1016/j.lungcan.2020.04.020.
URI
https://scholars.duke.edu/individual/pub1440388
PMID
32361034
Source
epmc
Published In
Lung Cancer (Amsterdam, Netherlands)
Volume
144
Published Date
Start Page
40
End Page
48
DOI
10.1016/j.lungcan.2020.04.020

Correlative Analyses of the SARC028 Trial Reveal an Association Between Sarcoma-Associated Immune Infiltrate and Response to Pembrolizumab.

PURPOSE: We recently reported a 17.5% objective RECIST 1.1 response rate in a phase II study of pembrolizumab in patients with advanced sarcoma (SARC028). The majority of responses occurred in undifferentiated pleomorphic sarcoma (UPS) and dedifferentiated liposarcoma (DDLPS). We sought to determine whether we can identify immune features that correlate with clinical outcomes from tumor tissues obtained pre- and on-treatment. PATIENTS AND METHODS: Pretreatment (n = 78) and 8-week on-treatment (n = 68) tumor biopsies were stained for PD-L1 and multiplex immunofluorescence panels. The density of positive cells was quantified to determine associations with anti-PD-1 response. RESULTS: Patients that responded to pembrolizumab were more likely to have higher densities of activated T cells (CD8+ CD3+ PD-1+) and increased percentage of tumor-associated macrophages (TAM) expressing PD-L1 pre-treatment compared with non-responders. Pre-treatment tumors from responders also exhibited higher densities of effector memory cytotoxic T cells and regulatory T cells compared with non-responders. In addition, higher density of cytotoxic tumor-infiltrating T cells at baseline correlated with a better progression-free survival (PFS). CONCLUSIONS: We show that quantitative assessments of CD8+ CD3+ PD-1+ T cells, percentage of TAMs expressing PD-L1, and other T-cell densities correlate with sarcoma response to pembrolizumab and improved PFS. Our findings support that multiple cell types present at the start of treatment may enhance tumor regression following anti-PD-1 therapy in specific advanced sarcomas. Efforts to confirm the activity of pembrolizumab in an expansion cohort of patients with UPS/DDLPS are underway.
Authors
Keung, EZ; Burgess, M; Salazar, R; Parra, ER; Rodrigues-Canales, J; Bolejack, V; Van Tine, BA; Schuetze, SM; Attia, S; Riedel, RF; Hu, J; Okuno, SH; Priebat, DA; Movva, S; Davis, LE; Reed, DR; Reuben, A; Roland, CL; Reinke, D; Lazar, AJ; Wang, W-L; Wargo, JA; Tawbi, HA
MLA Citation
Keung, Emily Z., et al. “Correlative Analyses of the SARC028 Trial Reveal an Association Between Sarcoma-Associated Immune Infiltrate and Response to Pembrolizumab.Clin Cancer Res, vol. 26, no. 6, Mar. 2020, pp. 1258–66. Pubmed, doi:10.1158/1078-0432.CCR-19-1824.
URI
https://scholars.duke.edu/individual/pub1427273
PMID
31900276
Source
pubmed
Published In
Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
Volume
26
Published Date
Start Page
1258
End Page
1266
DOI
10.1158/1078-0432.CCR-19-1824

SU2C-SARC032: A phase II randomized controlled trial of neoadjuvant pembrolizumab with radiotherapy and adjuvant pembrolizumab for high-risk soft tissue sarcoma.

Authors
Mowery, YM; Ballman, KV; Riedel, RF; Brigman, BE; Attia, S; Meyer, CF; Schuetze, S; Burgess, MA; Chmielowski, B; Dickson, MA; Hartner, LP; Milhem, MM; Tinoco, G; Van Tine, BA; Wagner, AJ; Reinke, DK; Kirsch, DG
MLA Citation
Mowery, Yvonne Marie, et al. “SU2C-SARC032: A phase II randomized controlled trial of neoadjuvant pembrolizumab with radiotherapy and adjuvant pembrolizumab for high-risk soft tissue sarcoma.Journal of Clinical Oncology, vol. 36, no. 15_suppl, American Society of Clinical Oncology (ASCO), 2018, pp. TPS11588–TPS11588. Crossref, doi:10.1200/jco.2018.36.15_suppl.tps11588.
URI
https://scholars.duke.edu/individual/pub1441415
Source
crossref
Published In
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Volume
36
Published Date
Start Page
TPS11588
End Page
TPS11588
DOI
10.1200/jco.2018.36.15_suppl.tps11588