LTBK-01: PROSPECTIVE, MULTI-CENTER PHASE III TRIAL OF TUMOR TREATING FIELDS TOGETHER WITH TEMOZOLOMIDE COMPARED TO TEMOZOLOMIDE ALONE IN PATIENTS WITH NEWLY DIAGNOSED GLIOBLASTOMA

Tumor Treating Fields (TTFields) is an established, frequency-tuned, anti-mitotic, physical treatment modality that acts in metaphase, anaphase and telophase. TTFields are delivered to the brain by a patient operated, portable medical device (Optune™, Novocure Ltd.). An international, multicenter, prospective, randomized phase 3 trial (EF-14) was initiated in 2009 to test the efficacy and safety of combining TTFields with temozlomide (TMZ) compared to TMZ alone following radiation therapy with adjuvant TMZ in patients with newly diagnosed GBM. Results of a protocol pre-specified successful interim analysis on the first 315 patients randomized has been reported (Stupp et al. JAMA 2015). Here we report the main outcomes of all 695 patients enrolled with a mature minimum follow-up of 18 month (median follow-up 36 months) for all patients (Range 19–80 months). Within 7 weeks after the end of TMZ/RT and stratification for extent of resection and MGMT status patients were randomized (at a 1:2 ratio) to either standard adjuvant TMZ alone (150–200 mg/m2/d x 5d) or TMZ and continuous administration of TTFields. Eligible patients had a newly diagnosed GBM, non-progressive after concomitant chemoradiotherapy, a performance status of ≥70%, and adequate hematological, liver and renal function. The primary endpoint of the study is progression free survival (PFS) as determined by blinded central radiology review; overall survival (OS) is a powered secondary endpoint. A total of 695 patients were randomized from 7/2009 – 11/2014. Patient characteristics are balanced, median age was 56 years (range 19–83), 87 % had undergone prior tumor resection and 13 % a biopsy only. 37% of tumors were MGMT methylated. Median time from end of radiotherapy to randomization was 37 days. The median number of adjuvant (maintenance) TMZ cycles 6 and 5 cycles, for TTFields/TMZ and TMZ alone, respectively. All analyses are intent-to-treat. The median progression-free survival was 6.7 months (95%CI 6.1–8.1) for the patients treated with TTFields/TMZ versus 4.0 months (CI 3.8 – 4.3) for TMZ alone (hazard ratio 0.63, p<0.00005). Median overall survival from randomization is 21 months versus 16 months for the TTFields/TMZ and TMZ alone, respectively, with a hazard ratio of 0.65 (CI 0.54–0.79), p<0.00062. The respective 2, 3 and 4-year survival rates are 43% (CI 38–47%) and 30% (CI 24–37), 24% (CI 19–29) and 16% (CI 11–23), 17% (CI 13–23) and 10% (CI 6–18); p<0.05 for all time points. This first and mature analysis of the full cohort of all randomized patients confirms and improves upon the superior results of TTFields/TMZ compared to TMZ alone seen in the trial’s interim analysis. The addition of TTFields to maintenance TMZ significantly extends both median and long term survival of patients with glioblastoma. The magnitude of survival benefit seen is equivalent to that seen for addition of TMZ to radiation which established TMZ as the standard of care for 1st line glioblastoma over a decade ago.

Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.