Tumor-treating fields plus temozolomide versus temozolomide alone for GBM patients
Standard adjuvant therapy after GBM resection is radiation therapy (RT) with concomitant temozolomide (TMZ) followed by maintenance TMZ. Tumor-treating fields (TTFields), consisting of low-intensity, alternating electric fields delivered via transducer arrays applied to the scalp. Addition of tumor-treating fields to maintenance TMZ was assessed in a Phase III multi-center, randomized controlled trial: 695 patients (83 centers, 2009-14) were randomized 2:1 to TTFields + TMZ (466) or TMZ alone (229). After RT, TTfields were delivered using 4 transducer arrays connected to a portable device in combination with TMZ (5 days per 28 days cycle for 6-12 cycles). Progression-free survival (PFS) and overall survival (OS) were the primary outcome measures, and analysis was performed for the intent-to-treat population. The +TTFields group showed statistically significant improvement compared with the temozolomide alone group in both median PFS (6.7 vs 4.0 months) and median OS (20.9 months vs 16.0 months). A major limitation is that TTField arrays must be worn on a shaved scalp and connected to a portable battery for over 20 hours per day. This and other potential impacts on quality of life (QOL) were not assessed. Randomization also occurred 3.8 months after diagnosis, thereby excluding patients with early (< 3 months) GBM recurrence, resulting in a subset of GBM patients with a better prognosis. Although the current trial demonstrated that addition of TTFields to TMZ promisingly improved PFS and OS, treating physicians should consider the study limitations, and also the important QOL effects when recommending this novel treatment modality.