Veliparib combined with adjuvant temozolomide therapy is not associated with a significant improvement in overall survival (OS) or progression-free survival (PFS) in patients with newly diagnosed MGMT hypermethylated glioblastoma, according to a randomized phase 2/3 trial.

However, data presented at the 2022 ASCO Annual Meeting suggest that a subset of patients treated with temozolomide plus veliparib may have extended survival following retreatment with temozolomide at first recurrence. 

In this phase 2/3 trial ( Identifier: NCT02152982), patients with newly diagnosed MGMT promoter hypermethylated glioblastoma who had completed concurrent radiation and temozolomide were randomly assigned to receive adjuvant therapy with temozolomide (days 1-5 q28 days) plus either placebo or veliparib (days 1-7 q28 days). Each treatment was continued for up to 6 cycles.

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There were 447 patients enrolled in the trial and used for this intention-to-treat analysis. The 2 treatment groups were well balanced for prognostic factors. 

Treatment was considered well tolerated overall. However, significantly higher rates of neutropenia, thrombocytopenia, and anemia were seen in patients who received veliparib.

The median OS was 28.1 months in the veliparib arm and 24.8 months in the placebo arm, which was not a statistically significant difference. The median PFS was similar between the arms as well, at 12.1 months in the placebo arm and 13.2 months in the veliparib arm.

However, there was a notable trend toward extended OS with temozolomide plus veliparib at intermediate time points between 24 months and 42 months. The 3-year OS rate was 37% in the veliparib arm and 29% in the placebo arm (P =.09). 

The study also revealed that retreatment with temozolomide at the time of first recurrence was associated with extended post-recurrence OS for patients treated with veliparib (P =.03). The median post-recurrence OS with temozolomide salvage was 17.0 months in the veliparib arm and 12.6 months in the placebo arm, compared with 9.6 months in both arms without temozolomide salvage.

According to the study authors, these data suggest a possible effect of veliparib limiting the emergence of temozolomide resistance in a subset of patients.

Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.  


JN, Ballman KV, Kizilbash SH, et al. Randomized phase II/III trial of veliparib or placebo in combination with adjuvant temozolomide in newly diagnosed glioblastoma (GBM) patients with MGMT promoter hypermethylation (Alliance A071102). Presented at ASCO 2022; June 3-7, 2022. Abstract 2001.