Tumor Growth Rate (TGR) Analysis Predicts Survival in a Multicenter Phase II Study of the PARP Inhibitor Pamiparib (BGB-290) with Temozolomide in Recurrent IDH-Mutant Gliomas (ABTC-1801)

Benjamin M Ellingson; Timothy F Cloughesy; Xiaobu Ye; Ashley Teraishi; Catalina Raymond; Sonoko Oshima; Francesco Sanvito; Patrick Y Wen; Tobias Walbert; Jian L Campian; L Burt Nabors; Byram H Ozer; Arati Desai; Antonio Omuro; Serena Desideri; Neeraja Danda; Stuart A Grossman; Ranjit S Bindra; David Schiff

doi:10.3174/ajnr.A9438

Tumor Growth Rate (TGR) Analysis Predicts Survival in a Multicenter Phase II Study of the PARP Inhibitor Pamiparib (BGB-290) with Temozolomide in Recurrent IDH-Mutant Gliomas (ABTC-1801)

AJNR Am J Neuroradiol. 2026 May 29:ajnr.A9438. doi: 10.3174/ajnr.A9438. Online ahead of print.

Authors

Benjamin M Ellingson¹, Timothy F Cloughesy², Xiaobu Ye², Ashley Teraishi², Catalina Raymond², Sonoko Oshima², Francesco Sanvito², Patrick Y Wen², Tobias Walbert², Jian L Campian², L Burt Nabors², Byram H Ozer², Arati Desai², Antonio Omuro², Serena Desideri², Neeraja Danda², Stuart A Grossman², Ranjit S Bindra², David Schiff²

Affiliations

¹ From the UCLA Brain Tumor Imaging Laboratory, Department of Radiological Sciences (B.M.E., A.T., C.R., S.O., F.S.), UCLA Brain Tumor Program, Department of Neurology (T.F.C.), David Geffen School of Medicine, University of California Los Angeles, CA; Johns Hopkins University (X.Y., S.D., N.D., S.A.G.), Baltimore, MD; Dana-Farber Cancer Institute (P.Y.W.), and Mass General Brigham Cancer Institute, Boston, MA; Hermelin Brain Tumor Center (T.W.), Henry Ford Health, Wayne State and Michigan State University, Detroit, MI, USA; Department of Medicine (J.L.C.), Division of Oncology, Washington University School of Medicine, St Louis, MO, USA; Department of Neurology (L.B.N.), University of Alabama at Birmingham, Birmingham, AB, USA; Department of Hematology and Medical Oncology (B.H.O.), Emory University School of Medicine, Atlanta, GA, USA; Department of Medical Oncology (A.D.), University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA; Department of Neurology and Neurological Sciences (A.O.), Stanford University School of Medicine, Palo Alto, CA, USA; Department of Therapeutic Radiology (R.S.B.), Yale School of Medicine, New Haven, CT, USA and Division of Neuro-Oncology (D.S.), University of Virginia School of Medicine. bellingson@mednet.ucla.edu.
² From the UCLA Brain Tumor Imaging Laboratory, Department of Radiological Sciences (B.M.E., A.T., C.R., S.O., F.S.), UCLA Brain Tumor Program, Department of Neurology (T.F.C.), David Geffen School of Medicine, University of California Los Angeles, CA; Johns Hopkins University (X.Y., S.D., N.D., S.A.G.), Baltimore, MD; Dana-Farber Cancer Institute (P.Y.W.), and Mass General Brigham Cancer Institute, Boston, MA; Hermelin Brain Tumor Center (T.W.), Henry Ford Health, Wayne State and Michigan State University, Detroit, MI, USA; Department of Medicine (J.L.C.), Division of Oncology, Washington University School of Medicine, St Louis, MO, USA; Department of Neurology (L.B.N.), University of Alabama at Birmingham, Birmingham, AB, USA; Department of Hematology and Medical Oncology (B.H.O.), Emory University School of Medicine, Atlanta, GA, USA; Department of Medical Oncology (A.D.), University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA; Department of Neurology and Neurological Sciences (A.O.), Stanford University School of Medicine, Palo Alto, CA, USA; Department of Therapeutic Radiology (R.S.B.), Yale School of Medicine, New Haven, CT, USA and Division of Neuro-Oncology (D.S.), University of Virginia School of Medicine.

PMID: 42217836
DOI: 10.3174/ajnr.A9438

Abstract

Background and purpose: Mutations in isocitrate dehydrogenase (IDH) lead to production of the oncometabolite 2-hydroxygluterate (2-HG), which suppresses homologous recombination and induces poly (ADP-ribose) polymerase (PARP) inhibitor sensitivity. Preclinical studies demonstrate that IDH-mutant gliomas are sensitive to PARP inhibition. Tumor growth rate (TGR) assessment offers a novel approach to evaluate treatment effects beyond traditional response criteria. Here, we report the change in TGR in a multicenter phase Ib/II study of the PARP inhibitor pamiparib with low-dose temozolomide in recurrent IDH-mutant gliomas, and evaluate TGR as an independent prognostic biomarker for overall survival.

Materials and methods: In this Adult Brain Tumor Consortium multicenter phase Ib/II clinical trial (ABTC-1801; NCT03914742), patients with recurrent IDH-mutant gliomas were enrolled in three cohorts: Arm A (grade 2-3, failed ≥2 alkylators), Arm B (grade 2-3, failed single alkylator ≥12 months prior), and an exploratory cohort of grade 4 IDH-mutant patients. All patients received pamiparib 60mg twice daily with temozolomide 20mg daily. Tumor growth rates were assessed using serial MRI FLAIR measurements before and during treatment. Growth rate inhibition was defined as a decrease in TGR after treatment compared to pre-treatment growth rate.

Results: Among evaluable patients in the dose expansion cohorts enrolled between 2020-2022, 45.5% (5/11) in Arm A, 30% (6/20) in Arm B, and 30% (3/10) in the grade 4 arm demonstrated a decrease in TGR during treatment relative to pre-treatment TGRs. Cox regression analysis showed that higher post-treatment TGR (HR=1.0065 [95%CI:1.0031-1.01], P=0.0002; Arms A-B, HR=1.0068 [95%CI:1.0027-1.011], P=0.0012) and an increase in TGR after treatment were significantly associated with shorter survival for all patients as well as when only including grades 2-3 gliomas in Arms A-B (All patients, HR=1.007 [95%CI:1.0032-1.0107], P=0.0003; Arms A-B, HR=1.008 [95%CI:1.0034-1.0126], P=0.0006). Patients with TGR change >+25 mL/6 months had significantly worse survival compared to those with TGR <+25 mL/6 months (HR=4.946, P=0.0044; Arms A-B, HR=3.210, P=0.0108).

Conclusions: TGR changes were significantly associated with survival outcomes, suggesting that growth stabilization may be an important metric for assessing treatment benefit in IDH-mutant gliomas.