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Clinical Trial
. 2024 Dec 1;10(12):1637-1644.
doi: 10.1001/jamaoncol.2024.4361.

Efficacy of Adding Veliparib to Temozolomide for Patients With MGMT-Methylated Glioblastoma: A Randomized Clinical Trial

Jann N Sarkaria  1 , Karla V Ballman  1 , Sani H Kizilbash  1 , Erik P Sulman  2 , Caterina Giannini  1 , Bret B Friday  3 , Nicholas A Butowski  4 , Nimish A Mohile  5 , David E Piccioni  6 , James D Battiste  7 , Jan Drappatz  8 , Jian L Campian  1 , Sandeep Mashru  9 , Kurt A Jaeckle  10 , Barbara J O'Brien  11 , Jesse G Dixon  1 , Brian F Kabat  1 , Nadia L Laack  1 , Leland S Hu  12 , Timothy Kaufmann  1 , Priya Kumthekar  13 , Benjamin M Ellingson  14 , S Keith Anderson  1 , Evanthia Galanis  1
Affiliations
Clinical Trial

Efficacy of Adding Veliparib to Temozolomide for Patients With MGMT-Methylated Glioblastoma: A Randomized Clinical Trial

Jann N Sarkaria et al. JAMA Oncol. .

Erratum in

  • Errors in Figures 2 and 3.
    [No authors listed] [No authors listed] JAMA Oncol. 2024 Dec 1;10(12):1736. doi: 10.1001/jamaoncol.2024.6238. JAMA Oncol. 2024. PMID: 39699606 Free PMC article. No abstract available.
  • Errors in Visual Abstract.
    [No authors listed] [No authors listed] JAMA Oncol. 2025 Apr 1;11(4):435. doi: 10.1001/jamaoncol.2025.0254. JAMA Oncol. 2025. PMID: 39976934 Free PMC article. No abstract available.

Abstract

Importance: The prognosis for patients with glioblastoma is poor following standard therapy with surgical resection, radiation, temozolomide, and tumor-treating fields.

Objectives: To evaluate the combination of veliparib and temozolomide in glioblastoma based on preclinical data demonstrating significant chemosensitizing effects of the polyadenosine diphosphate-ribose polymerase 1/2 inhibitor veliparib when combined with temozolomide.

Design, setting, and participants: Patients with newly diagnosed glioblastoma with MGMT promoter hypermethylation who had completed concomitant radiation and temozolomide were enrolled between December 15, 2014, and December 15, 2018, in this Alliance for Clinical Trials in Oncology trial. The data for this analysis were locked on April 21, 2023.

Interventions: Patients were randomized and treated with standard adjuvant temozolomide (150-200 mg/m2 orally, days 1-5) combined with either placebo or veliparib (40 mg orally, twice daily, days 1-7) for 6 cycles.

Main outcomes and measures: The primary end point for the phase 3 portion of the trial was overall survival (OS).

Results: There were 322 patients randomized during the phase 2 accrual period and an additional 125 patients randomized to complete the phase 3 accrual, for a total of 447 patients in the final phase 3 analysis. The median (range) age for patients was 60 (20-85) years and 190 patients (42.5%) were female. The median OS was 24.8 months (90% CI, 22.6-27.7) for the placebo arm and 28.1 months (90% CI, 24.3-33.3) for the veliparib arm (P = .17). The difference in survival did not meet the prespecified efficacy end point. However, there was a separation of the survival curves that favored the veliparib arm over 24 to 48 months of follow-up. The experimental combination was well tolerated with an acceptable elevation in grade 3 or 4 hematologic toxic effects.

Conclusions and relevance: This trial found that adding veliparib to adjuvant temozolomide did not significantly extend OS in patients with newly diagnosed, MGMT-hypermethylated glioblastoma.

Trial registration: ClinicalTrials.gov Identifier: NCT02152982.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Sarkaria reported grants from GlaxoSmithKline, Curtana, Bayer, Wayshine, Black Diamond, Karyopharm, Boston Scientific, Wugen, Rain Therapeutics, Sumitomo Dainippon Pharma Oncology, AbbVie, SKBP, Boehringer Ingelheim, AstraZeneca, ABL Bio, ModifiBio, Inhibrx, Otomagnetics, and Reglagene outside the submitted work. Dr Ballman reported grants from the National Cancer Institute (NCI) during the conduct of the study. Dr Kizilbash reported grants from Orbus Therapeutics, Apollomics, Wayshine Biopharma, LOXO Oncology, Nerviano Medical Sciences, CNS Pharmaceuticals, Aminex Therapeutics, Celgene, SonALAsense, and Hutchinson Medipharma; scientific advisory board service for SK Life Sciences; and consulting fees from Sichuan Honghe Biotechnology outside the submitted work. Dr Sulman reported grants from NCI during the conduct of the study as well as grants from Novocure outside the submitted work. Dr Mohile reported grants from Novocure Inc outside the submitted work. Dr Drappatz reported equity in Gilead and Pfizer outside the submitted work. Dr O'Brien reported grants from the Alliance for Clinical Trials in Oncology during the conduct of the study as well as personal fees from Plus Therapeutics outside the submitted work. Dr Dixon reported grants from NCI during the conduct of the study. Dr Hu reported medical advisory board service for Imaging Biometrics, personal fees from Bayer, and being a cofounder of Precision Oncology Insights during the conduct of the study as well as a patents 10909675, 11341649, and 11861475 issued and overseen by Mayo Clinic Ventures outside the submitted work. Dr Kumthekar reported personal fees from Enclear Therapies, Belay Diagnostics, Plus Therapeutics, Servier, Novocure, Biocept, Janssen, Bioclinica, Mirati, Telix Pharmaceuticals, Seagen, BPGbio DMSC, and IN8bio outside the submitted work. Dr Ellingson reported personal fees from Alpheus Medical, Carthera, Chimerix, Erasca, Global Coalition for Adaptive Research, Imaging Endpoints, Medicenna, Voiant, Monteris, Neosoma, Orbus Therapeutics, Sagimet Biosciences, Sapience Therapeutics, Servier Pharmaceuticals, SonALAsense, Sumitomo Dainippon Pharma Oncology, and Third Rock Ventures and grants from Siemens during the conduct of the study. Dr Galanis reported personal fees from Kiyatec, Karyopharm, Boehringer Ingelheim, and Boston Scientific as well as grants from Servier Pharmaceuticals, Denovo Biopharma, Celgene, and MedImmune outside the submitted work. No other disclosures were reported.

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