Regimen fails to extend survival in glioblastoma subset
Click Here to Manage Email Alerts
CHICAGO — The addition of veliparib to adjuvant temozolomide did not extend OS or PFS among patients with newly diagnosed MGMT hypermethylated glioblastoma, according to results of a randomized phase 2/phase 3 trial presented at ASCO Annual Meeting.
However, certain patients treated with the combination may survive longer after retreatment with temozolomide at first recurrence, results showed.
“This is interesting and certainly hypothesis generating data,” Jann N. Sarkaria, MD, physician-scientist and professor of radiation oncology at Mayo Clinic in Rochester, Minnesota, said during a presentation.
Background and methods
Poly(ADP-ribose) polymerase (PARP) is a key modulator of DNA repair after treatment with temozolomide.
Preclinical work showed a significant survival benefit with the combination of temozolomide and veliparib (ABT-888, AbbVie) — a PARP inhibitor — in xenografts derived from patients with glioblastoma and MGMT promoter hypermethylation.
Sarkaria and colleagues conducted the Alliance A071102 trial to assess the combination for this patient population.
All study participants had newly diagnosed disease, ECOG performance status of 2 or less and had completed radiation therapy and temozolomide.
The analysis included 447 patients.
Researchers randomly assigned 223 patients (median age, 61 years; 43% women; 89% white, 3% Black) to adjuvant temozolomide on days 1 to 5 every 28 days plus veliparib twice daily on days 1 to 7. The other 224 patients (median age, 60 years; 42% women; 88% white; 5% Black) received temozolomide plus placebo.
The groups were balanced with regard to percentage of patients aged younger than 70 years (83% for veliparib vs. 84% for placebo), completion of gross total resection (63% vs. 62%), percentage of patients with ECOG performance status of 0 or 1 (92% each), and planned use of Optune (Novocure [16% vs. 17%]).
OS served as the primary endpoint. PFS served as a secondary endpoint.
Results
Median follow-up was 57.8 months.
The combination appeared well-tolerated, Sarkaria said.
A significantly higher percentage of patients assigned veliparib than placebo experienced grade 3 or higher neutropenia (30% vs. 4%), thrombocytopenia (15% vs. 10%) or anemia (4% vs. 0%; P < .001 for all). A numerically higher percentage of patients assigned veliparib experienced grade 3 or higher lymphopenia (32% vs. 14%).
Researchers reported no significant differences between the veliparib and placebo groups with regard to OS (median, 28.1 months vs. 24.8 months; HR = 0.89; 95% CI, 0.71-1.11) or PFS (median, 13.2 months vs. 12.1 months; HR = 1.05; 95% CI, 0.86-1.29).
Researchers observed a late separation of OS curves after 18 months, with 36-month OS rates of 37% in the veliparib group and 29% in the placebo group. However, the curves overlapped again by 48 months.
Results of an unplanned exploratory analysis showed treatment with temozolomide at first recurrence appeared associated with longer post-recurrence OS among patients who received the experimental regimen.
Sarkaria and colleagues reported median post-recurrence OS with temozolomide salvage of 17 months among those who received veliparib-temozolomide and 12.6 months among those who received placebo-temozolomide, compared with median post-recurrence OS of 9.6 months among patients who did not receive temozolomide salvage.
“These data are consistent with a possible effect of veliparib limiting the emergence of temozolomide resistance in a subset of [patients with glioblastoma],” Sarkaria and colleagues wrote.
Researchers plan to analyze biobanked samples in hopes of identifying biomarkers that may predict which patients would derive the most benefit from the regimen, Sarkaria said.
Collapse
Sarkaria JN, et al. Abstract 2001. Presented at: ASCO Annual Meeting; June 3-7, 2022; Chicago.
Read more about
Click Here to Manage Email Alerts