Scalp-Sparing Radiation With Concurrent Temozolomide and Tumor Treating Fields (SPARE) for Patients With Newly Diagnosed Glioblastoma

Abstract

IntroductionStandard-of-care treatment for patients with newly diagnosed glioblastoma (GBM) after surgery or biopsy includes concurrent chemoradiation followed by maintenance temozolomide (TMZ) with tumor treating fields (TTFields). Preclinical studies suggest TTFields and radiotherapy work synergistically. We report the results of our trial evaluating the safety of TTFields used concurrently with chemoradiation.MethodsThis is a single-arm pilot study (clinicaltrials.gov Identifier: NCT03477110). Adult patients (age ≥ 18 years) with newly diagnosed glioblastoma and a Karnofsky performance score (KPS) of ≥ 60 were eligible. All patients received concurrent scalp-sparing radiation (60 Gy in 30 fractions) with TMZ (75 mg/m2 daily) and TTFields (200 kHz). Maintenance therapy included TMZ and continuation of TTFields. Scalp-sparing radiation treatment was used to reduce radiation dermatitis. Radiation treatment was delivered through the TTFields arrays. The primary endpoint was safety and toxicity of tri-modality treatment within 30 days of completion of chemoradiation treatment.ResultsThere were 30 patients enrolled, including 20 (66.7%) men and 10 (33.3%) women, with a median age of 58 years (range 19 to 77 years). Median KPS was 90 (range 70 to 100). A total of 12 (40%) patients received a gross total resection and 18 (60%) patients had a subtotal resection. A total of 12 (40%) patients had multifocal disease at presentation. There were 20 (66.7%) patients who had unmethylated O(6)-methylguanine-DNA-methyltransferase (MGMT) promotor status and 10 (33.3%) patients who had methylated MGMT promoter status. Median follow-up was 15.2 months (range 1.7 to 23.6 months). Skin adverse events were noted in 83.3% of patients, however, these were limited to Grade 1 or 2 events, which resolved spontaneously or with topical medications. The primary end point was met; no TTFields discontinuation occurred during the evaluation period due to high grade scalp toxicity. A total of 27 (90%) patients had progression, with a median progression-free survival (PFS) of 9.3 months (95% confidence interval (CI): 8.5-11.6 months). The 1-year progression-free survival was 23% (95% CI: 12%-45%). The median overall survival (OS) was 15.8 months (95% CI: 12.5 months-infinity). The 1-year overall survival was 66% (95% CI: 51%-86%).ConclusionsConcurrent TTFields with scalp-sparing chemoradiation is a feasible and well-tolerated treatment option with limited toxicity. A phase 3, randomized clinical trial (EF-32, clinicaltrials.gov Identifier: NCT04471844) investigating the clinical benefit of concurrent TTFields with chemoradiation treatment is currently enrolling.Clinical Trial RegistrationClinicaltrials.gov, identifier NCT03477110.

Tumor treating fields affect mesothelioma cell proliferation by exerting histotype-dependent cell cycle checkpoint activations and transcriptional modulations

“…It is attractive to speculate that these transcriptional effects could be exploited to design mechanism-based synergistic combinations. In this respect it is worthwhile underlining that among the genes that were found modulated by TTFields there are some involved in DNA repair and DNA damage response, supporting the rational to combine TTFields with drugs causing DNA damage or radiotherapy, and some recent preclinical and clinical evidences support this hypothesis [ 12 , 23 , 24 ].…”

Therapeutic potential of tumor treating fields for malignant brain tumors

“… 73 When TTFields were given concurrently with RT which was delivered through the TTFields arrays and with maintenance TMZ, the PFS of 9.3 months was illustrated. 72 It follows that the feasibility of TTFields both as maintenance therapy and alongside chemoradiotherapy is endorsed by prior clinical practice, and a more large‐scale clinical trial, EF‐32(NCT04471844), is underway.…”

Tumor-Treating Fields in Glioblastomas: Past, Present, and Future

“…In addition, Stein et al [ 95 ] reported a case of thalamic GBM, IDH wild-type, showing a complete radiological response after chemoradiation with TMZ, proton boost therapy, and TMZ maintenance in combination with TTFields therapy. Recently, Miller et al [ 96 ] evaluated the skin toxicity of scalp-sparing chemoradiation plus TTFields followed by maintenance TMZ plus TTFields in 30 patients with ndGBMs, showing good tolerance of the new protocol with no need to remove electric arrays during the radiation process, as well as a higher PFS in these patients than in the historical controls.…”