It might look fancy and sound futuristic, but scientists have come up with a wearable, electric skull cap that generates electric fields to treat brain tumors. Novocure’s medical device Optune generates small-range alternating electric fields (tumor treating fields, or TTFs) that pulse through the scalp to interfere with rapidly dividing cells. Optune was first approved by the FDA in 2011 for recurrent glioblastoma, an aggressive form of brain cancer. In 2015, the FDA expanded Optune’s label to include newly diagnosed glioblastoma (in combination with standard temozolomide chemotherapy) based on interim efficacy data from the Phase III EF-14 trial. Final results from this pivotal trial were presented by Dr. Roger Stupp on the second day of the 2017 American Association of Cancer Research (AACR) annual meeting, held in Washington, DC1.
The EF-14 trial randomized newly diagnosed glioblastoma patients who had completed standard treatment (surgery, temozolomide and radiation, dubbed the “Stupp protocol”) to receive adjuvant temozolomide with or without Optune. Long-term data in all 695 randomized patients had already been reported last year, showing a 37% reduction in the risk of death with Optune plus temozolomide versus temozolomide alone (overall survival [OS] was a secondary end point) and that the efficacy benefit was seen in all prespecified patient subgroups2. At this year’s AACR meeting, Dr. Stupp reported landmark 5-year OS rates: 13% for patients in the device arm versus 5% in the control arm. These results denote an unprecedented long-term OS benefit in newly diagnosed glioblastoma, for which the community has waited for more than a decade.
The OS benefit might seem modest and this is a long shot from what we could call a “cure,” but glioblastoma is such a difficult-to-treat disease that any positive development is noteworthy. There is a dearth of treatment options for glioblastoma relative to other oncology indications, and we’ve witnessed a number of recent high-profile failures in the late-phase pipeline. Just a few days ago, Bristol-Myers Squibb reported that its flagship immune checkpoint inhibitor Opdivo failed to beat Avastin, the only agent approved for recurrent glioblastoma, in a Phase III (CheckMate-143) OS trial (of note, other late-phase trials of Opdivo are still ongoing in the newly diagnosed setting)3. While data from CheckMate-143 are yet to be presented, this event exemplifies yet again that drug development is notoriously difficult in glioblastoma. In that context, the results for Optune in newly diagnosed patients are certainly positive.
Glioblastoma is the only oncology indication for which a medical device generating TTFs is approved. Combining TTFs with chemotherapy is an original approach when compared with conventional cancer treatment modalities. Nevertheless, some patients may find this therapy to be inconvenient and to negatively impact quality of life—indeed, patients need to shave their heads periodically and wear the device for at least 18 hours per day. The technology is being assessed in other tumor types, and it remains to be seen whether TTFs can provide a new treatment option beyond glioblastoma in the clinic.
- Hefi ME, et al. Tumor treating fields added to standard chemotherapy in newly diagnosed glioblastoma (GBM): final results of a randomized, multi-center, Phase III trial. Proceedings of the AACR Annual Meeting. Abstract CT007.
- Stupp R, et al. Prospective, multi-center Phase III trial of tumor treating fields together with temozolomide compared to temozolomide alone in patients with newly diagnosed glioblastoma to convert case. Proceedings of the Society for Neuro-Oncology Annual Meeting. 2016. Abstract LTBK-01.
- Bristol-Myers Squibb, press release, April 3, 2017.