A novel therapeutic option for glioblastoma is being met with guarded enthusiasm based on the results of the randomized phase III EF-14 trial that demonstrated a 2.9-month improvement in the primary endpoint of progression-free survival (PFS) and a 2.8-month improvement in overall survival (OS) with the addition of the tumor treating fields (TTFields) device to adjuvant temozolomide, according to results presented Tuesday, June 2, during the Central Nervous System Tumors Oral Abstract Session (Abstract 2000).
Although the 2.9-month improvement in PFS appears modest, it is actually quite substantial in this underserved population with very aggressive disease—so much so that the study’s Independent Data Monitoring Committee recommended early closure of the trial following a prespecified interim analysis conducted with 315 patients.
TTFields is unlike any other therapy currently used for cancer treatment. “It’s a completely new concept of treating the tumor and will be met with great skepticism,” said EF-14 lead investigator Roger Stupp, MD, of University Hospital Zurich and University of Zurich, Switzerland.
Dr. Roger Stupp
The portable, home-use medical device resembles a swimmer’s cap with insulated electrodes lining the interior. When placed on a shaved scalp, TTFields delivers low-intensity, intermediate-frequency alternating electrical fields to the brain that exert selective toxicity in proliferating cells through antimitotic mechanisms. TTFields lends itself to treatment of glioblastoma because the majority of cells in the brain are typically non-proliferating.
A total of 700 patients with newly diagnosed supratentorial glioblastoma who had completed concomitant chemoradiotherapy and demonstrated no tumor progression enrolled in the multicenter EF-14 trial. They were randomly assigned in a 2:1 ratio to daily use of TTFields plus adjuvant temozolomide or adjuvant temozolomide alone. The median time from diagnosis to random selection in both arms was 3.8 months.
Median PFS reached 4.2 months with adjuvant temozolomide alone but improved to 7.1 months when daily use of the TTFields device was added (hazard ratio [HR] 0.69, 95% CI [0.56, 0.86]; p = 0.0010), thus meeting the primary study endpoint. The use of TTFields also increased OS from a median of 16.6 months to 19.4 months (HR 0.75, 95% CI [0.60, 0.96]; p = 0.0222). In turn, this bumped the 2-year survival rate from 29% to 43%. These findings from the full data set of 695 patients were consistent with those from the interim analysis of 315 patients.
TTFields proved both safe and tolerable. Aside from mild device-related skin reactions at the site of administration, patients experienced no significant increase in toxicity with the addition of TTFields. Importantly, the occurrence of nervous system and psychiatric events remained similar in the two treatment arms.
“We have a new standard of care for patients with glioblastoma,” Dr. Stupp said, based on the findings. “But beyond that, we have a new cancer treatment modality well beyond neuro-oncology we have now to evaluate in the cancer field.”
Debate ensued after Dr. Stupp’s talk as to whether the field of oncology is ready for TTFields. Discussant Martin J. van den Bent, MD, of Erasmus MC Daniel den Hoed Cancer Centre, the Netherlands, said that the fact that the study was stopped early and that patients in the control arm were allowed to crossover to receive TTFields may obscure the device’s true OS benefit.
“We have to ask the question, ‘Is it worth the cost?’ [Treatment with the device] is estimated at $20,000 per month,” Dr. van den Bent said. “We need to realize that not all treatments are cost-beneficial and will be widely used and accepted. That is the question here.”
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