Addition of Optune device to temozolomide improves OS in glioblastoma
A wearable medical device designed to deliver alternating electrical fields administered in addition to temozolomide chemotherapy improved survival in patients with glioblastoma, according to results from the phase 3 EF-14 trial presented at the American Association for Cancer Research Annual Meeting.
“Glioblastoma is the deadliest primary malignancy of the central nervous system for adults,” Roger Stupp, MD, professor of neurological surgery at Northwestern University Feinberg School of Medicine and associate director for strategic initiatives at the Robert H. Lurie Comprehensive Cancer Center of Northwestern University, said in a press release. “The last time any form of treatment was shown to improve survival for patients with this disease was more than 10 years ago, when adding temozolomide to radiotherapy was shown to improve the 2-year survival rate from 10% to 27%.”
Tumor-treating fields (Optune, Novocure) — a novel, antimitotic, physical treatment — delivers alternating electrical fields at an intermediate frequency of 200 MHz (1-3 V/cm) continuously to the brain by a patient-operated, wearable medical device.
“We found that patients learned how to operate the device very quickly, often in less than an hour,” Stupp said.
The researchers conducted an international, multicenter, prospective, randomized phase 3 trial to evaluate the addition of tumor-treating fields to standard adjuvant temozolomide chemotherapy in 695 patients with newly diagnosed glioblastoma. The FDA approved the Optune medical device for the treatment of newly diagnosed glioblastoma based on interim data from the first 315 patients enrolled in the trial.
PFS served as the primary endpoint, and OS served as the secondary endpoint.
Within 7 weeks after the end of concomitant chemoradiotherapy (median time to randomization, 37 days), researchers randomly assigned patients 1:2 to receive standard adjuvant temozolomide alone (n = 229) or with tumor-treating fields (n = 466).
Patients treated with tumor-treating fields demonstrated superior PFS (6. 7 months; 95% CI, 6.1-8.1) compared with those treated with temozolomide alone (4 months; 95% CI, 3.8-4.4; HR = 0.63; P = .00005).
The tumor-treating fields group also showed superior median OS (20.9 months vs. 16 months; HR = 0.63; 95% CI, 0.53-0.76).
Survival rates for patients who received tumor-treating fields plus temozolomide were significantly improved at 2 years (43% vs. 31%; P = .0008), 3 years (26% vs. 16%), 4 years (20% vs. 8%) and 5 years (13% vs. 5%; P = .0037).
Significant improvement in OS occurred in all patient subgroups, regardless of age, extent of resection, performance status, gender, geography or MGMT methylation status.
“It is very exciting to see that the magnitude of benefit from adding tumor-treating fields to temozolomide is similar to that seen from adding temozolomide to radiotherapy; the 2-year survival rate for those in the tumor-treating fields plus temozolomide arm was 43%,” Stupp said. “These data show the power of this new treatment modality, and we look forward to learning the results of trials testing it in patients with other forms of cancer.”
The magnitude of improvement following the addition of tumor-treating fields to temozolomide appeared comparable to the benefit observed with temozolomide 12 years ago.
The researchers noted this may define a new standard of care in the treatment of glioblastoma.
“Tumor-treating fields are an entirely new treatment modality,” Stupp said. “We need to continue to think outside the box to find other new treatments and then we need to learn how best to combine them with existing treatment modalities to ensure maximum patient benefit.” – by Kristie L. Kahl
Stupp R, et al. Tumor treating fields added to standard chemotherapy in newly diagnosed glioblastoma (GBM): Final results of a randomized, multi-center, phase III trial. Presented at: American Association for Cancer Research Annual Meeting; April 1-5, 2017; Washington.
Disclosure: The study was funded by NovoCure. Stupp reports travel support from NovoCure and advisory board roles with EMD Serono, Merck, Novartis, Pfizer and Roche.