A phase II/III clinical trial has revealed that the addition of veliparib to temozolomide did not significantly improve overall survival in patients with newly diagnosed glioblastoma exhibiting MGMT promoter hypermethylation. The study, a double-blind trial conducted by the Alliance for Clinical Trials in Oncology, raises questions about the efficacy of veliparib in this specific patient population.
The trial enrolled 447 patients across multiple U.S. sites between December 2014 and May 2018. All patients had received concomitant radiation and temozolomide before being randomized to receive either adjuvant temozolomide plus placebo (n = 224) or adjuvant temozolomide plus veliparib (n = 223). Veliparib was administered at 40 mg twice daily on days 1 to 7 every 28 days for six cycles, while temozolomide was given at 150 to 200 mg/m2 on days 1 to 5. The primary endpoint was overall survival.
Key Findings on Survival
After a median follow-up of 73.6 months, the median overall survival was 28.1 months (90% CI = 24.3–33.3 months) in the veliparib group and 24.8 months (90% CI = 22.6–27.7 months) in the control group. The hazard ratio was 1.07 (95% CI = 0.88–1.30, P = .17), indicating no statistically significant difference between the two groups. Notably, a separation of survival curves favoring the veliparib group was observed at 24 to 48 months, with a 3-year survival rate of 36.8% in the veliparib arm versus 29.0% in the control arm; however, this difference did not translate to a statistically significant improvement in overall survival.
Adverse Events
The addition of veliparib to temozolomide was associated with a higher incidence of hematologic adverse events. Grade ≥ 3 hematologic adverse events occurred in 49.8% of patients in the veliparib group compared to 23.5% in the control group. Grade ≥ 3 nonhematologic adverse events were reported in 22.6% and 27.7% of the veliparib and control groups, respectively. One death, considered possibly related to treatment, occurred in the veliparib group due to a thromboembolic event.
Implications of the Study
The study's findings suggest that veliparib does not provide a significant survival benefit when added to adjuvant temozolomide in patients with newly diagnosed, MGMT- hypermethylated glioblastoma. These results do not support the routine use of veliparib in this setting. Further research may be warranted to explore potential benefits in specific subgroups or with different treatment regimens.
