PMID- 36590015
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230722
IS  - 2666-3643 (Electronic)
IS  - 2666-3643 (Linking)
VI  - 4
IP  - 1
DP  - 2023 Jan
TI  - A Phase 1 Safety Study of Avelumab Plus Stereotactic Body Radiation Therapy in 
      Malignant Pleural Mesothelioma.
PG  - 100440
LID - 10.1016/j.jtocrr.2022.100440 [doi]
LID - 100440
AB  - INTRODUCTION: Single-agent monoclonal antibody therapy against programmed 
      death-ligand 1 (PD-L1) has modest effects in malignant pleural mesothelioma. 
      Radiation therapy can enhance the antitumor effects of immunotherapy. 
      Nevertheless, the safety of combining anti-PD-L1 therapy with stereotactic body 
      radiation therapy (SBRT) is unknown. We present the results of a phase 1 trial to 
      evaluate the safety of the anti-PD-L1 antibody avelumab plus SBRT in patients 
      with malignant pleural mesothelioma. METHODS: This was a single-arm, 
      investigator-initiated trial in patients who progressed on prior chemotherapy. 
      Avelumab was delivered every other week, and SBRT was delivered to one lesion in 
      three to five fractions (minimum of 30 Gy) followed by continuation of avelumab 
      up to 24 months or until disease progression. The primary end point of the study 
      was safety on the basis of grade 3+ nonhematologic adverse events (AEs) within 3 
      months of SBRT. RESULTS: Thirteen assessable patients received a median of seven 
      cycles (range: 2-26 cycles) of avelumab. There were 27 grade 1, 17 grade 2, four 
      grade 3, and no grade 4 or 5 avelumab-related AEs. The most common were 
      infusion-related allergic reactions (n = 6), anorexia or weight loss (n = 6), 
      fatigue (n = 6), thyroid disorders (n = 5), diarrhea (n = 3), and myalgia or 
      arthralgias (n = 3). There were 10 grade 1, four grade 2, one grade 3, and no 
      grade 4 or 5 SBRT-related AEs. The most common were diarrhea (n = 3), chest 
      pain/myalgia (n = 2), fatigue (n = 2), cough (n = 2), dyspnea (n = 2), and 
      nausea/vomiting (n = 2). CONCLUSIONS: Combination avelumab plus SBRT seems 
      tolerable on the basis of the prespecified toxicity end points of the first stage 
      of this Simon two-stage design phase 1 study.
CI  - (c) 2022 The Authors.
FAU - Rimner, Andreas
AU  - Rimner A
AD  - Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, Weill 
      Cornell Medical Center, New York, New York.
FAU - Adusumilli, Prasad S
AU  - Adusumilli PS
AD  - Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, 
      Weill Cornell Medical Center, New York, New York.
FAU - Offin, Michael D
AU  - Offin MD
AD  - Thoracic Oncology Service, Department of Medicine, Memorial Sloan Kettering 
      Cancer Center, Weill Cornell Medical Center, New York, New York.
FAU - Solomon, Stephen B
AU  - Solomon SB
AD  - Department of Radiology, Memorial Sloan Kettering Cancer Center, Weill Cornell 
      Medical Center, New York, New York.
FAU - Ziv, Etay
AU  - Ziv E
AD  - Department of Radiology, Memorial Sloan Kettering Cancer Center, Weill Cornell 
      Medical Center, New York, New York.
FAU - Hayes, Sara A
AU  - Hayes SA
AD  - Department of Radiology, Memorial Sloan Kettering Cancer Center, Weill Cornell 
      Medical Center, New York, New York.
FAU - Ginsberg, Michelle S
AU  - Ginsberg MS
AD  - Department of Radiology, Memorial Sloan Kettering Cancer Center, Weill Cornell 
      Medical Center, New York, New York.
FAU - Sauter, Jennifer L
AU  - Sauter JL
AD  - Department of Pathology, Memorial Sloan Kettering Cancer Center, Weill Cornell 
      Medical Center, New York, New York.
FAU - Gelblum, Daphna Y
AU  - Gelblum DY
AD  - Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, Weill 
      Cornell Medical Center, New York, New York.
FAU - Shepherd, Annemarie F
AU  - Shepherd AF
AD  - Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, Weill 
      Cornell Medical Center, New York, New York.
FAU - Guttmann, David M
AU  - Guttmann DM
AD  - Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, Weill 
      Cornell Medical Center, New York, New York.
FAU - Eichholz, Jordan E
AU  - Eichholz JE
AD  - Thoracic Oncology Service, Department of Medicine, Memorial Sloan Kettering 
      Cancer Center, Weill Cornell Medical Center, New York, New York.
FAU - Zhang, Zhigang
AU  - Zhang Z
AD  - Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer 
      Center, Weill Cornell Medical Center, New York, New York.
FAU - Ritter, Erika
AU  - Ritter E
AD  - Department of Immune Monitoring Core Facility, Memorial Sloan Kettering Cancer 
      Center, Weill Cornell Medical Center, New York, New York.
FAU - Wong, Phillip
AU  - Wong P
AD  - Department of Immune Monitoring Core Facility, Memorial Sloan Kettering Cancer 
      Center, Weill Cornell Medical Center, New York, New York.
FAU - Iqbal, Afsheen N
AU  - Iqbal AN
AD  - Thoracic Oncology Service, Department of Medicine, Memorial Sloan Kettering 
      Cancer Center, Weill Cornell Medical Center, New York, New York.
FAU - Daly, Robert M
AU  - Daly RM
AD  - Thoracic Oncology Service, Department of Medicine, Memorial Sloan Kettering 
      Cancer Center, Weill Cornell Medical Center, New York, New York.
FAU - Namakydoust, Azadeh
AU  - Namakydoust A
AD  - Thoracic Oncology Service, Department of Medicine, Memorial Sloan Kettering 
      Cancer Center, Weill Cornell Medical Center, New York, New York.
FAU - Li, Henry
AU  - Li H
AD  - Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, Weill 
      Cornell Medical Center, New York, New York.
FAU - McCune, Megan
AU  - McCune M
AD  - Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, Weill 
      Cornell Medical Center, New York, New York.
FAU - Gelb, Emily H
AU  - Gelb EH
AD  - Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, Weill 
      Cornell Medical Center, New York, New York.
FAU - Taunk, Neil K
AU  - Taunk NK
AD  - Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, Weill 
      Cornell Medical Center, New York, New York.
FAU - von Reibnitz, Donata
AU  - von Reibnitz D
AD  - Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, Weill 
      Cornell Medical Center, New York, New York.
FAU - Tyagi, Neelam
AU  - Tyagi N
AD  - Department of Medical Physics, Memorial Sloan Kettering Cancer Center, Weill 
      Cornell Medical Center, New York, New York.
FAU - Yorke, Ellen D
AU  - Yorke ED
AD  - Department of Medical Physics, Memorial Sloan Kettering Cancer Center, Weill 
      Cornell Medical Center, New York, New York.
FAU - Rusch, Valerie W
AU  - Rusch VW
AD  - Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, 
      Weill Cornell Medical Center, New York, New York.
FAU - Zauderer, Marjorie G
AU  - Zauderer MG
AD  - Thoracic Oncology Service, Department of Medicine, Memorial Sloan Kettering 
      Cancer Center, Weill Cornell Medical Center, New York, New York.
LA  - eng
GR  - P30 CA008748/CA/NCI NIH HHS/United States
GR  - R01 CA236615/CA/NCI NIH HHS/United States
PT  - Journal Article
DEP - 20221201
PL  - United States
TA  - JTO Clin Res Rep
JT  - JTO clinical and research reports
JID - 101769967
PMC - PMC9801123
OTO - NOTNLM
OT  - Avelumab
OT  - Malignant pleural mesothelioma
OT  - Phase I Study
OT  - Safety
OT  - Stereotactic body radiation therapy
EDAT- 2023/01/03 06:00
MHDA- 2023/01/03 06:01
PMCR- 2022/12/01
CRDT- 2023/01/02 04:14
PHST- 2022/09/14 00:00 [received]
PHST- 2022/11/11 00:00 [revised]
PHST- 2022/11/17 00:00 [accepted]
PHST- 2023/01/02 04:14 [entrez]
PHST- 2023/01/03 06:00 [pubmed]
PHST- 2023/01/03 06:01 [medline]
PHST- 2022/12/01 00:00 [pmc-release]
AID - S2666-3643(22)00164-3 [pii]
AID - 100440 [pii]
AID - 10.1016/j.jtocrr.2022.100440 [doi]
PST - epublish
SO  - JTO Clin Res Rep. 2022 Dec 1;4(1):100440. doi: 10.1016/j.jtocrr.2022.100440. 
      eCollection 2023 Jan.