Chemoradiation Treatment with or without Concurrent Tumor-Treating Fields (TTFields) in Patients with Newly Diagnosed Glioblastoma (GBM)

Abstract

<h3>Purpose/Objective(s)</h3> The standard of care for newly diagnosed glioblastoma (GBM) after maximal safe resection or biopsy includes concurrent temozolomide (TMZ) and radiation therapy (RT) followed by adjuvant Tumor Treating Fields (TTF) and maintenance TMZ. Preclinical studies suggest TTF and radiotherapy work synergistically. We evaluate the clinical benefit of concurrent TTF with CRT vs adjuvant TTF with TMZ after CRT. <h3>Materials/Methods</h3> Concurrent TTF with CRT patients were enrolled in a single-arm pilot study (clinicaltrials.gov Identifier: NCT03477110). For the comparison control of adjuvant TTF, adult patients age ≥ 18 years with newly diagnosed histologically-confirmed GBM that had a KPS ≥ 60 who received treatment with CRT and adjuvant TMZ + TTF from three institutions were included. The adjuvant TTF cohort excluded patients who progressed during CRT or did not receive TMZ. PFS and OS were compared between concurrent and adjuvant TTF patients. The impact of molecular mutations PTEN and TP53 were also evaluated. <h3>Results</h3> A total of 87 patients were enrolled in this study, of which 30 received concurrent TTF with CRT. Median patient age was 58 (range; 19-77) in the concurrent TTF group and 59 (range; 31-78) in the adjuvant TTF group. The median KPS in both groups was 90 (range 70-100 in concurrent, 60-100 in adjuvant). MGMT methylation was present in 33.3% (10) of the concurrent TTF and 32.0% (16) in the adjuvant TTF group. 40% (12) received GTR in the concurrent group and 38% (19) received GTR in the adjuvant group. Multifocal disease was appreciated in 40% (12) of patients in the concurrent TTF group, with one patient having gliomatosis. There is no significant difference in median OS, 17.1 months in the concurrent group and 19.4 months in the adjuvant group (p=0.38 [95% CI: 0.66-1.94]). There was also no significant difference in PFS, 10.2 months in the concurrent group and 9.7 months in the adjuvant group (p=0.76 [95%CI: 0.60-1.53]). Mutations in PTEN or TP53 did not impact OS or PFS of current vs adjuvant TTF treatment. <h3>Conclusion</h3> There is no OS or PFS difference between concurrent or adjuvant TTF treatment in patients diagnosed with glioblastoma in the current study. However, the adjuvant TTF group is considered to be a better prognostic group due to the elimination of patients that progressed or declined after initial CRT. The current study suggests concurrent TTF treatment may improve the outcome of a worse prognosis group to be similar to that of a better prognosis group. The survival benefit of concurrent TTF with CRT vs adjuvant TTF is being tested in the phase 3 TRIDENT EF 32 clinical trial (NCT04471844).