FDA Panel Recommends Pre-Market Approval of Portable Electric System for Recurrent Glioblastoma

A panel of experts convened by the US Food and Drug Administration to evaluate neurological devices recommended approval of the NovoTTF-100A system for pre-market use in patients with recurrent supratentorial glioblastoma multiforme (GBM). After reviewing final data from the phase III EF-11 trial, the 12-member panel returned 7 yes votes and 3 no votes, with 2 abstentions, on the question of whether the device’s benefits outweighed its risks.

 

In the EF-11 trial, 237 previously treated patients with recurrent or persistent GBM were randomly assigned to noninvasive treatment with the NovoTTF system or physician's choice of chemotherapy. According to a press release from NovoCure, the Israeli company that manufactures NovoTTF, the rate of response (RR) was significantly higher among patients treated with NovoTTF and they were significantly more likely to be progression-free at 6 months than patients in the chemotherapy arm.

 

The RR was 14% in the NovoTTF group compared with 10% in the chemotherapy arm. At 6 months, disease had not progressed in 21% of patients treated with NovoTTF versus 15% of patients taking chemotherapy. The device was also associated with superior quality of life scores and fewer adverse events. Median overall survival (OS) was reportedly similar between the groups.

 

At the Society for Neuro-Oncology Annual Scientific Meeting in November 2010, investigators presented data on survival for a subgroup of patients aged <60 years with a Karnofsky performance score >80%. Median OS for these patients was 8.8 months in the NovoTTF group versus 6.6 months in the chemotherapy arm (P <.01). The 1-year rate of survival was also significantly better in the NovoTTF group than the chemotherapy arm (35% vs 20%, respectively; P <.01). The most frequent adverse event observed in study participants assigned to NovoTTF was a rash at the site of electrode placement, which investigators said resolved with steroid treatment.

 

Some panel members expressed concern as to whether trial results were biased by the investigator’s decision to censor data for patients unable to complete 4 weeks of treatment with the device. They also had reservations about the design of the device, which some described as flawed. The FDA panel unanimously agreed that the device was safe but split evenly over its effectiveness, requiring chairman Robert Hurst MD, professor of radiology, Hospital of the University of Pennsylvania to cast a tiebreaking vote; Hurst voted in support of its effectiveness.

 

NovoTTF is a battery-operated device that delivers low levels of electric current to the tumor via electrodes attached to the scalp. In vitro studies suggest that the electricity interrupts cell division, which causes apoptosis and results in slow or arrested tumor growth. The patient wears the 6-pound device in a backpack or satchel, typically for 18 hours at a time. NovoTTF is already used in Europe to treat recurrent GBM, a particularly aggressive type of brain cancer.

 

Several patients with GBM attended the hearing, with 46-year-old Scott Johnson of Minden, Louisiana, testifying that he had been using NovoTTF for 14 months during a clinical trial and it allowed him to resume his life. He said chemotherapy had left him tired and weak.

 

NovoCure is planning to conduct another phase III multinational study that will randomize patients to receive NovoTTF combined with temozolomide (Temodar) or temozolomide alone. It is also being investigated in patients with advanced non–small cell lung cancer.