PMID- 34728525
OWN - NLM
STAT- MEDLINE
DCOM- 20220322
LR  - 20240211
IS  - 1557-3265 (Electronic)
IS  - 1078-0432 (Print)
IS  - 1078-0432 (Linking)
VI  - 28
IP  - 3
DP  - 2022 Feb 1
TI  - A Phase II Study of the Efficacy and Safety of Oral Selinexor in Recurrent 
      Glioblastoma.
PG  - 452-460
LID - 10.1158/1078-0432.CCR-21-2225 [doi]
AB  - PURPOSE: Selinexor is an oral selective inhibitor of exportin-1 (XPO1) with 
      efficacy in various solid and hematologic tumors. We assessed intratumoral 
      penetration, safety, and efficacy of selinexor monotherapy for recurrent 
      glioblastoma. PATIENTS AND METHODS: Seventy-six adults with Karnofsky Performance 
      Status >/= 60 were enrolled. Patients undergoing cytoreductive surgery received up 
      to three selinexor doses (twice weekly) preoperatively (Arm A; n = 8 patients). 
      Patients not undergoing surgery received 50 mg/m(2) (Arm B, n = 24), or 60 mg 
      (Arm C, n = 14) twice weekly, or 80 mg once weekly (Arm D; n = 30). Primary 
      endpoint was 6-month progression-free survival rate (PFS6). RESULTS: Median 
      selinexor concentrations in resected tumors from patients receiving presurgical 
      selinexor was 105.4 nmol/L (range 39.7-291 nmol/L). In Arms B, C, and D, 
      respectively, the PFS6 was 10% [95% confidence interval (CI), 2.79-35.9], 7.7% 
      (95% CI, 1.17-50.6), and 17% (95% CI, 7.78-38.3). Measurable reduction in tumor 
      size was observed in 19 (28%) and RANO-response rate overall was 8.8% [Arm B, 
      8.3% (95% CI, 1.0-27.0); C: 7.7% (95% CI, 0.2-36.0); D: 10% (95% CI, 2.1-26.5)], 
      with one complete and two durable partial responses in Arm D. Serious adverse 
      events (AEs) occurred in 26 (34%) patients; 1 (1.3%) was fatal. The most common 
      treatment-related AEs were fatigue (61%), nausea (59%), decreased appetite (43%), 
      and thrombocytopenia (43%), and were manageable by supportive care and dose 
      modification. Molecular studies identified a signature predictive of response 
      (AUC = 0.88). CONCLUSIONS: At 80 mg weekly, single-agent selinexor induced 
      responses and clinically relevant PFS6 with manageable side effects requiring 
      dose reductions. Ongoing trials are evaluating safety and efficacy of selinexor 
      in combination with other therapies for newly diagnosed or recurrent 
      glioblastoma.
CI  - (c)2021 The Authors; Published by the American Association for Cancer Research.
FAU - Lassman, Andrew B
AU  - Lassman AB
AUID- ORCID: 0000-0001-7386-9928
AD  - Division of Neuro-Oncology, Department of Neurology, Columbia University Vagelos 
      College of Physicians and Surgeons and NewYork-Presbyterian, New York, New York. 
      ABL7@cumc.columbia.edu.
AD  - Herbert Irving Comprehensive Cancer Center, Columbia University Vagelos College 
      of Physicians and Surgeons and NewYork-Presbyterian, New York, New York.
FAU - Wen, Patrick Y
AU  - Wen PY
AD  - Dana-Farber Cancer Institute, Boston, Massachusetts.
FAU - van den Bent, Martin J
AU  - van den Bent MJ
AUID- ORCID: 0000-0001-5710-5127
AD  - Erasmus MC Cancer Institute, University Medical Center Rotterdam, Rotterdam, the 
      Netherlands.
FAU - Plotkin, Scott R
AU  - Plotkin SR
AUID- ORCID: 0000-0002-6109-6419
AD  - Cancer Center and Department of Neurology, Massachusetts General Hospital, 
      Boston, Massachusetts.
FAU - Walenkamp, Annemiek M E
AU  - Walenkamp AME
AUID- ORCID: 0000-0003-4958-8960
AD  - University of Groningen, University Medical Center Groningen, Groningen, the 
      Netherlands.
FAU - Green, Adam L
AU  - Green AL
AD  - Morgan Adams Foundation Pediatric Brain Tumor Research Program, University of 
      Colorado School of Medicine and Children's Hospital Colorado, Aurora, Colorado.
FAU - Li, Kai
AU  - Li K
AD  - Karyopharm Therapeutics Inc, Newton, Massachusetts.
FAU - Walker, Christopher J
AU  - Walker CJ
AD  - Karyopharm Therapeutics Inc, Newton, Massachusetts.
FAU - Chang, Hua
AU  - Chang H
AD  - Karyopharm Therapeutics Inc, Newton, Massachusetts.
FAU - Tamir, Sharon
AU  - Tamir S
AUID- ORCID: 0000-0003-0820-1184
AD  - Karyopharm Therapeutics Inc, Newton, Massachusetts.
FAU - Henegar, Leah
AU  - Henegar L
AD  - Karyopharm Therapeutics Inc, Newton, Massachusetts.
FAU - Shen, Yao
AU  - Shen Y
AD  - DarwinHealth Inc, New York, New York.
FAU - Alvarez, Mariano J
AU  - Alvarez MJ
AD  - DarwinHealth Inc, New York, New York.
AD  - Department of Systems Biology, Columbia University, New York, New York.
FAU - Califano, Andrea
AU  - Califano A
AUID- ORCID: 0000-0003-4742-3679
AD  - Herbert Irving Comprehensive Cancer Center, Columbia University Vagelos College 
      of Physicians and Surgeons and NewYork-Presbyterian, New York, New York.
AD  - Department of Systems Biology, Columbia University, New York, New York.
AD  - Department of Biomedical Informatics, Columbia University, New York, New York.
AD  - Department of Biochemistry and Molecular Biophysics, Columbia University, New 
      York, New York.
AD  - Department of Medicine, Vagelos College of Physicians and Surgeons, Columbia 
      University, New York, New York.
FAU - Landesman, Yosef
AU  - Landesman Y
AD  - Karyopharm Therapeutics Inc, Newton, Massachusetts.
FAU - Kauffman, Michael G
AU  - Kauffman MG
AD  - Karyopharm Therapeutics Inc, Newton, Massachusetts.
FAU - Shacham, Sharon
AU  - Shacham S
AD  - Karyopharm Therapeutics Inc, Newton, Massachusetts.
FAU - Mau-Sorensen, Morten
AU  - Mau-Sorensen M
AUID- ORCID: 0000-0003-2235-1250
AD  - Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
LA  - eng
GR  - UG1 CA189960/CA/NCI NIH HHS/United States
GR  - S10 OD012351/OD/NIH HHS/United States
GR  - P30 CA013696/CA/NCI NIH HHS/United States
GR  - U01 CA217858/CA/NCI NIH HHS/United States
GR  - K08 NS102532/NS/NINDS NIH HHS/United States
GR  - S10 OD021764/OD/NIH HHS/United States
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20211102
PL  - United States
TA  - Clin Cancer Res
JT  - Clinical cancer research : an official journal of the American Association for 
      Cancer Research
JID - 9502500
RN  - 0 (Hydrazines)
RN  - 0 (Triazoles)
RN  - 31TZ62FO8F (selinexor)
SB  - IM
MH  - Administration, Oral
MH  - Adult
MH  - Aged
MH  - Brain/metabolism
MH  - Brain Neoplasms/*drug therapy/surgery
MH  - Cytoreduction Surgical Procedures
MH  - Female
MH  - Glioblastoma/*drug therapy/surgery
MH  - Humans
MH  - Hydrazines/*administration & dosage/adverse effects/metabolism
MH  - Male
MH  - Middle Aged
MH  - Neoplasm Recurrence, Local/*drug therapy
MH  - Treatment Outcome
MH  - Triazoles/*administration & dosage/adverse effects/metabolism
MH  - Young Adult
PMC - PMC8810630
MID - NIHMS1754532
EDAT- 2021/11/04 06:00
MHDA- 2022/03/23 06:00
PMCR- 2022/08/24
CRDT- 2021/11/03 05:58
PHST- 2021/06/21 00:00 [received]
PHST- 2021/09/10 00:00 [revised]
PHST- 2021/10/27 00:00 [accepted]
PHST- 2021/11/04 06:00 [pubmed]
PHST- 2022/03/23 06:00 [medline]
PHST- 2021/11/03 05:58 [entrez]
PHST- 2022/08/24 00:00 [pmc-release]
AID - 1078-0432.CCR-21-2225 [pii]
AID - CCR-21-2225 [pii]
AID - 10.1158/1078-0432.CCR-21-2225 [doi]
PST - ppublish
SO  - Clin Cancer Res. 2022 Feb 1;28(3):452-460. doi: 10.1158/1078-0432.CCR-21-2225. 
      Epub 2021 Nov 2.