Patients with newly diagnosed glioblastoma saw improved progression-free survival when treated with tumor treating fields, pembrolizumab, and temozolomide versus historical control data.
Tumor treating fields (TTFields) plus pembrolizumab (Keytruda) and temozolomide (Temodar) for patients with newly diagnosed glioblastoma showed improved median progression-free survival (PFS) versus historical control data for TTFields and temozolomide alone, according to results from the phase 2 2-THE-TOP trial (NCT03405792) presented at the Society for Neuro-Oncology (SNO) 2021 Annual Meeting.
At more than 9 months of follow-up, median PFS was 11.2 months with 24% of patients having a complete or partial response. The median follow-up was 14.7 months.
“These data show that tumor treating fields have the potential to activate the pathways needed to create an effective, anti-cancer environment in the tumor. The results published today suggest a potential paradigm shift in how we approach treatment of patients with newly diagnosed glioblastoma,” Ely Benaim, MD, Novocure’s chief medical officer, said in the press release.
A total of 25 patients were enrolled who had a median age of 61 years. In both groups, there were 8 patients each (32%) who had a biopsy only and partial resection. A total of 18 patients (72%) had unmethylated MGMT and 3 (12%) patients had an IDH mutation.
Eligibility criteria included histological confirmation of grade IV glioblastoma, MGMT methylation status, and previous receipt of maximal safe resection and radiotherapy concomitant with temozolomide.
At follow-up, a total of 12 patients were progression free (48%) and 15 (60%) were still alive. Additionally, 6 patients (24%) who had measurable tumors had a partial or complete responses.
Before patients received pembrolizumab, 193,760 peripheral blood mononuclear cells were sequenced in 12 patients. In 11 patients, there was robust TTFields T-cell activation found through the T1FN trajectory and correlation with TCRαβ clonal expansion Simpson index (Spearman coefficient r = _0.8; P = .014).
The most common adverse effects were thrombosis in 4 patients (16%), seizure in 3 (12%), and metabolic disturbances in 2 (8%).
A previous phase 3 trial, EF-14 (NCT00916409), which investigated patients who had received post radiation TTFields plus temozolomide compared with temozolomide alone was used as the historical control study. Patients in this trial experienced a median PFS at 6.7 months in the TTFields plus temozolomide group vs 4.0 months in the temozolomide monotherapy group. Patients had a median overall survival of 20.9 months in the TTFields group and 16.0 months in the temozolomide monotherapy group.
2-THE-TOP phase 2 trial reports positive top-line results in newly diagnosed glioblastoma. News Release. Novocure. November 15, 2021. Accessed November 16, 2021. https://bit.ly/3Fk8gmz