Impact of IDH1 mutation status on outcome in clinical trials for recurrent glioblastoma.
IDH1 mutated glioblastoma (GB) has a better prognosis than IDH1 wildtype GB. However, it remains unknown whether patients (pts) with IDH1 mutated GB have a higher 6-month progression free survival (PFS6) or radiographic response (RR) rate on clinical trials for recurrence. Retrospective review of GB pts at MDACC between 2006 and 2012 identified 330 patients in recurrent GB trials. 93 patients (28 %) had either PFS6 or a complete/partial RR per RANO criteria. 49/93 (53 %) patients with PFS6 or a complete/partial RR had tumor tissue for IDH1 testing. A matched cohort of 49 patients on recurrent GB clinical trials that failed to achieve PFS6 or RR (also with tissue for IDH1 testing) was identified for comparison. IDH1 status was obtained in 92/98 (94 %) patients of which 17 (18 %) had an IDH1 mutation. PFS6 was seen in 26/49 (53 %) patients. IDH status was unknown in two of these patients. 5/24 (21 %) were IDH1 mutated compared to 5/24 (21 %) of their matched cohort without PFS6. RR was found in 47/49 (94 %) patients. IDH status was unknown in four of these patients. IDH1 mutation was present in 7/43 (16 %) patients with RR compared to 10/43 (23 %) in the matched cohort without RR (p = 0.48). Median OS for trials at first recurrence was 9.8 months for IDH1 wildtype GB vs. 19.32 months for IDH1 mutated GB (p = 0.14). IDH1 mutation status was not predictive of PFS6 or RR in recurrent GB trials for this data set. However, further examination in larger randomized prospective studies is needed.
Department of Neurology, Baylor College of Medicine, One Baylor Plaza, MS NB302, Houston, TX, 77030, USA.
Jacob J
JJ
Mandel
Department of Neurosurgery, Medical College of South Carolina, 96 Jonathan Lucas St, Charleston, SC, 29425, USA.
David
D
Cachia
Quantitative Sciences-Unit 1409, The University of Texas MD Anderson Cancer Center, P.O. Box 301402, Houston, TX, 77230-1402, USA.
Diane
D
Liu
Division of Neuro-Oncology, Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd Unit 431, Houston, TX, 77030-4009, USA.
Charmaine
C
Wilson
Department of Pathology, University Health Network, Toronto Medical Discovery Tower, 101 College St., Rm 14-601, Toronto, ON, M5G 1L7, Canada.
Ken
K
Aldape
Division of Neuro-Oncology, Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd Unit 431, Houston, TX, 77030-4009, USA.
Greg
G
Fuller
Division of Neuro-Oncology, Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd Unit 431, Houston, TX, 77030-4009, USA. jdegroot@mdanderson.org.
John F
JF
de Groot
D000328:Adult; D000368:Aged; D001932:Brain Neoplasms / Q000175:diagnosis* / Q000235:genetics*; D002986:Clinical Trials as Topic; D018572:Disease-Free Survival; D005909:Glioblastoma / Q000175:diagnosis* / Q000235:genetics*; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis* / Q000235:genetics*; D012189:Retrospective Studies; D055815:Young Adult
D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human
Clinical trials; IDH1 mutation; Recurrent glioblastoma