In a phase II/III trial reported in JAMA Oncology, Sarkaria et al found that the addition of veliparib to temozolomide did not improve overall survival in patients with newly diagnosed glioblastoma with MGMT promoter hypermethylation.
Study Details
In the double-blind Alliance for Clinical Trials in Oncology trial, 447 patients included in the phase III analysis of overall survival were enrolled from multiple U.S. sites between December 2014 and October 2016 (phase II enrollment, n = 322 ) and between November 2017 and May 2018 (phase III enrollment, n = 125). Patients had received concomitant radiation and temozolomide. Patients were randomly assigned to receive adjuvant temozolomide at 150 to 200 mg/m2 on days 1 to 5 combined with placebo (n = 224) or veliparib at 40 mg twice daily on days 1 to 7 (n = 223) every 28 days for six cycles. The primary endpoint for the phase III portion of the trial was overall survival.
Key Findings
Median follow-up was 73.6 months. Median overall survival was 28.1 months (90% confidence interval [CI] = 24.3–33.3 months) in the veliparib group vs 24.8 months (90% CI = 22.6–27.7 months) in the control group (hazard ratio =1.07, 95% CI = 0.88–1.30, P = .17). A separation of survival curves favoring the veliparib group was observed at 24 to 48 months of follow-up, with the largest difference in rates being 36.8% vs 29.0% at 3 years.
Grade ≥ 3 hematologic adverse events occurred in 49.8% of the veliparib group vs 23.5% of the control group. Grade ≥ 3 nonhematologic adverse events were reported in 22.6% vs 27.7%. One death considered possibly related to treatment was observed, as a result of a thromboembolic event in a patient in the veliparib group.
The investigators concluded: “This trial found that adding veliparib to adjuvant temozolomide did not significantly extend [overall survival] in patients with newly diagnosed, MGMT-hypermethylated glioblastoma.”
Jann N. Sarkaria, MD, of the Mayo Clinic, Rochester, is the corresponding author of the JAMA Oncology article.
Disclosure: The study was supported by grants from the National Cancer Institute and others. For full disclosure of all study authors, visit JAMA Oncology.
