New dynamics! Tumor electric field therapy to treat glioblastoma has new results

Tumor Electric Field Therapy (TTFields) is a non-invasive anti-fistosion therapyIn a Phase III clinical study EF-14 for newly diagnosed glioblastoma patients, TTFields and TTFields (TTFields / TMZ) combination therapy significantly improved the patient's progressionless life (PFS) and total survival (OS) compared to single TMZThe authors analyzed compliance data from Patients in EF-14 to assess the improvement in PfS and OS by TTFields compliance, the results of which were published in journal of Neuro-Oncology in December 2018glioblastoma (GBM) is the most common and invasive adult brain tumor, accounting for 56% of all gliomas and 15% of all primary brain tumors, with an increase in annual incidence in the United States with ageStandard treatment for newly diagnosed GBM includes maximum surgical removal, supplemented by radiotherapy (RT) and assisted temequinamine (TMZ) chemotherapyHowever, glioblastoma is still not cured, the median survival of patients is only about 15 monthsTumor Field Therapy (TTFields) is a unique treatment method, through low-intensity, medium frequency (200 kHz) AC electric field, acting on the proliferation of cancer cells microtube protein, destroying the filamentof of glioma, inducing cell death, cell stress, and endoclusan stressTTFields inhibits DNA damage repair by lowering the DNA repair gene in the BRCA1 pathwayWhen combined with anti-PD-1 therapy, chemotherapy and radiotherapy, TTFields can also promote cell deathphase III clinical trial EF-11 in recurrent GBM showed that TTFields was safeAn in-depth analysis of EF-11 trial data showed a significant increase in the median OS of compliance of 75% (18 hours per day) compared to 75% of patients with complianceThe Phase III study OF EF-14 in the newly diagnosed GBM showed that TTFields plus maintenance dose TMZ therapy significantly improved PFS and OSHealth-related quality of life (HRQOL) did not decrease compared to single TMZBecause TTFields is effective and safe, the National Comprehensive Cancer Network (NCCN) recently recommended TTFields and TMZ as the standard Class 1 treatment option for the new diagnosis of GBMbut TTFields's treatment is very different from systemic treatmentTTFields has antitumor cells only when the transducer chip is placed on the scalp and continuously emits an AC electric field of a specific intensity (200KHz)TTFields therapy had no effect on normal cell division and had minimal systemic adverse reactions Therefore, in order to obtain good clinical treatment results, the most important thing is to improve patient compliance, strictly follow the TTFields treatment process this paper analyzes data on patients treated with TTFields-TMZ and TTMZ alone in EF-14 studies The EF-14 study was a randomized, open-label trial that included 695 newly diagnosed GBM patients who underwent standard simultaneous and complementary chemotherapy after surgical removal or biopsy Patients were randomly assigned to TTFields plus maintenance TMZ chemotherapy (n s 466) or TMZ alone (n s 229) Both groups of TMZ doses were 150-200 mg / m2, 5/28 for 6-12 courses The median time between diagnosis and randomization groupings was 3.8 months for both groups the subgroup analysis primarily assessed whether patients' compliance with TTFields could be used as an independent predictor of PFS and OS The internal electronic log extracted from each NovoTTF-100A (Optune ® ) device based on the derived data is defined as the percentage of the total planned treatment time that the device is actually used for treatment during the month researchers will first analyze patients with monthly compliance level s75% or 75%, and then refine statistical analysis according to the monthly compliance interval of 0 to 30%, 30% to 50%, 50% to .60%, 60% to .70%, 70% to .80%, 80% to 90%, 90% to 100% for more detailed statistical analysis use the Kaplan-Meier method to draw the PFS and OS survival curves The Cox scale risk model was used to analyze whether treatment compliance, gender, MGMT methylation status, excision state, KPS score, and country of residence (outside the United States and the United States) were independent predictors a total of 466 patients were randomly assigned to the TTFields Joint TMZ treatment group, and 229 patients were randomly assigned to the TMZ individual treatment group In the TTFields joint TMZ group, the majority of patients were male (68%), with a median age of 56 and KPS at 90% The MGFT promoter region methylation ratio was 36% in the TTFields joint TMZ group and 54% in the TMZ group alone overall, the study groups matched each other in baseline characteristics compared to single TMZ, the TTFields combined TMZ group received a longer PFS and OS, and patients should have at least 50% per month of compliance (Figure 1) Since then, pfsS and OS have been gradually extended as compliance has increased Figure 1 Compared to single TMZ, the TTFields combined TMZ group received a longer PFS and OS, and patients should have at least 50% monthly compliance (Figure 1) Since then, pfsS and OS have been gradually extended as compliance has increased if patients in the TTFields combined TMZ group had the highest monthly compliance rate of 90% (Figure 2), the median PFS in the TTFields combined TMZ group was 8.2 months and the OS was 24.9 months The single TMZ group is only PFS 4.0 months, OS 16.9 months The five-year survival rate was 29.3% when the patient compliance rate treated by TTFields in conjunction with TMZ was 90% (Figure 3) TTFields combined TMZ monthly treatment duration of 75% is an independent predictor of OS (p.0.031) Figure 2 When the treatment is dependent on 90%, TTFields-TMZ treatment can achieve maximum efficacy, with a median survival rate of up to 24.9 months (28.7 months from the beginning of diagnosis) from the beginning of treatment
3 When treatment of compliance is 90%, the annual survival rate of newly diagnosed GBM patients receiving TTFields-TMZ treatment is significantly higher than that of the single TTFields-TMZ group, and the survival rate is significantly higher than that of the tTFields-TMZ group, 5.32 years Follow-up analysis of EF-11 trial data showed that TTFields extended the median OS time in patients with relapsed GBM (7.7 vs 4.5 months; p 0.042) The early analysis found that the treatment compliance of patients treated with TTFields should be 75% Another study from the real world (PRiDe registry) also suggests that compliance of 75% helps extend the overall lifetime The results of this study further find that the compliance rate threshold of 75% is an independent related factor for the extension of survival The study showed that tTFields combined with TMZ treatment compliance in the newly diagnosed GROUP of GBM patients could significantly extend survival compared to tMZ alone a variety of social and clinical factors to help patients comply with TTFields treatment Although TTFields is non-invasive and Optune devices keep patients unaffected in their daily activities, starting TTFields treatment still requires some lifestyle changes compared to radiation therapy or other systemic therapy Some patients may be reluctant to comply with the requirement to shave each time a chip is replaced, and wearing a chip on the skinmay may cause some patients to be self-conscious and cause excessive attention to their condition More support from the family and society is needed The most common side effect in clinical trials is skin irritation In the EF-14 study, 52% of TTFields-TMZ patients reported mild-moderate skin irritation, including allergies, irritating dermatitis, ulcers, and skin lesions Most of these skin problems can be prevented by appropriate technology, skin care, and replacement of chips Effective skin care strategies help patients to maximize compliance with TTFields treatment and maintain a quality of life during treatment study showed that when TTFields combined with TMZ treatment, monthly compliance greater than 50%, it significantly improved patient survival than TMZ alone The higher the therapeutic compliance of TTFields in conjunction with TTMZ, the more associated it is associated with no progression and overall survival prolongation, indicating that TTFields treatment has dose response mechanisms and that the effect is independent of other prognostic factors (e.g KPS, age, and MGMT methylation status) In patients with compliance of more than 90 per cent, the median survival period from the beginning of treatment was 24.9 months (28.7 months from the time of diagnosis) REF : Toms SA, et al Journal of Neuro-Oncology Dec 2018 doi.org/10.1007/s11060-018-03057-z