The survival of glioblastoma has improved significantly! Electric field therapy combined with immunotherapy has great potential
A phase 2 trial data will be announced at the upcoming 2021 annual meeting of the Society of Neuro-Oncology (SNO). The results show that compared with the historical control data of the tumor electric field therapy (TTFields) + temozolomide (Temodar) regimen, patients with glioblastoma (GBM) are receiving tumor electric field therapy +When treated with Papolizumab (Keytruda) + temozolomide, the progression-free survival (PFS) was significantly improved.
Tumor electric fields (TTFields) primarily utilize electric fields to disrupt cancer cell division. In all preclinical studies to date, TTFields have demonstrated consistent antimitotic activity. TTFields therapy is mainly used in conjunction with other standard cancer treatments. Increasing evidence supports the broad applicability of TTFields to certain other cancer therapies, including radiotherapy, chemotherapy, and immunotherapy. In clinical studies to date, TTFields therapy has not demonstrated systemic toxicity; mild to moderate skin irritation is the most common side effect.
Research data on tumor electric field therapy
The 2-THE-TOP (NCT03405792) trial was a phase 2 pilot trial designed to treat newly diagnosed glioblastoma patients. A total of 25 patients with a median age of 61 years and a median follow-up of 14.7 months were enrolled. In each of the two groups, 8 patients (32%) underwent only biopsy and partial resection. A total of 18 patients (72%) had unmethylated MGMT, and 3 patients (12%) had IDH mutations. Patients enrolled in the trial underwent maximal tumor resection followed by standard chemoradiotherapy. After chemoradiotherapy, patients began monthly cycles of adjuvant temozolomide. Tumor-treating fields therapy was initiated approximately during the first cycle of adjuvant temozolomide. Immunotherapy pembrolizumab was introduced in the second cycle, followed by pembrolizumab every three weeks until the first disease progression or unacceptable toxicity.
At follow-up, 12 patients (48%) were progression-free and 15 (60%) were still alive. Additionally, 6 patients (24%) with measurable tumors had partial or complete responses. During follow-up of more than 9 months, the median progression-free survival was 11.2 months, with 24% of patients achieving complete or partial remission. 193,760 peripheral blood mononuclear cells from the 12 patients were sequenced prior to pembrolizumab administration. Strong T-cell activation was detected in 11 patients by T1FN trajectory and its correlation with the Simpson index of TCRαβ clonal expansion. The most common adverse events were thrombosis (4 patients, 16%), seizures (3 patients, 12%), and metabolic disturbances (2 patients, 8%).
The previous phase 3 trial EF-14 (NCT00916409) was a randomized, pivotal phase 3 trial comparing the efficacy of TTFields plus temozolomide after radiotherapy versus temozolomide alone for newly diagnosed glioblastoma. This trial was used as a historical control. In this trial, the median progression-free survival (PFS) was 6.7 months in the TTFields plus temozolomide group and 4.0 months in the temozolomide monotherapy group. The median overall survival was 20.9 months in the TTFields group and 16.0 months in the temozolomide monotherapy group.
Reminder: Research data show that tumor electric field therapy TTFields has the potential to activate the pathways needed to create an effective anti-cancer environment in tumors. In the future, the treatment methods of glioblastoma patients may undergo breakthrough changes. It is hoped that the therapy will obtain better trial results, be approved as soon as possible and be used clinically for the benefit of more cancer patients.
