The Optune Device by Novocure for Glioblastoma Multiforme
Here we are at the fourth episode of Ben Williams’ guide translation project on treatment options for Glioblastoma Multiforme. This is chapter 3 of the guide that talks about the Optune device by Novocure which unfortunately is not yet available in Italy as part of the standard treatment unlike what happens in the United States and several other states (e.g. Austria, Germany, Japan and Switzerland to name a few). My advice is again that you use this information to discuss with the medical team that is following you and you can also point them to the supporting scientific references. Enjoy the reading!
In the spring of 2011, the FDA approved the fourth-ever treatment for glioblastoma. Unlike the previous three (gliadel, temozolomide and Avastin), the new treatment does not involve drugs or surgery, but instead uses a “helmet” of electrodes that generates a low level of alternating electrical current. A biotechnology company called Novocure developed the device, called Optune, based on experimental findings that electromagnetic fields stop tumor growth by interfering with the mitotic phase of cell division, causing cancer cells to die instead of proliferate (138). Healthy brain cells rarely divide and are therefore not affected. The treatment involves the use of a collection of electrodes for 18 or more hours a day, which allows the patient to live almost normally.
Optune and chemoradiotherapy, the next standard of care?
EF-14 is a phase 3 randomized clinical trial for newly diagnosed glioblastoma that compared standard chemoradiotherapy combined with the use of the Optune device (NovoTTF) and monthly courses of Temodar, compared to chemoradiotherapy followed only by monthly courses of Temodar.
In November 2014, at the annual SNO meeting in Miami Beach, Roger Stupp gave a presentation in front of a large audience, describing the interim survival resulting from the EF-14 study, and essentially presenting what could become the new standard of care. for newly diagnosed glioblastoma. This study is the first major Phase 3 study since the “Stupp Protocol” was established in 2005 which reports a positive and statistically significant survival benefit for newly diagnosed glioblastoma. In fact, the study was so successful that it was stopped early and on December 2, Novocure announced that the FDA had approved an exemption supplement that allowed all patients in the control group in study EF-14 to also start receiving therapy with the Optune device for free.
The interim results presented in Miami were based on the first 315 patients enrolled in the study, who had at least 18 months of follow-up. Of these, 105 were randomized to the control arm and 210 were randomized to receive electric field therapy for cancer treatment. Survival and progression-free survival were measured from the time of randomization, which by standard of care had a median of 3.8 months from diagnosis. Median progression-free survival was 7.1 months in the Optune arm compared to 4 months in the control arm (hazard ratio 0.63, with a high degree of statistical significance, p = 0.001). Median overall survival from randomization was 19.6 months in the Optune arm compared to 16.6 months in the control arm (hazard ratio 0.75, statistically significant, p = 0.034). The 2-year survival was 43% in the Optune arm compared to 29% in the control arm. It should be borne in mind that all of these statistics are measured from randomization, approximately 4 months after diagnosis, meaning that the median overall survival in the Optune arm approaches 24 months from diagnosis. The above statistics refer to the intent-to-treat (ITT) population, which includes all randomized patients, as opposed to the treated population (per protocol), which excludes patients who have not started the second temozolomide course or have had major protocol violations.
On October 5, 2015, a press release announced that the FDA had approved Optune in combination with temozolomide for the newly diagnosed glioblastoma, almost a year after the first survival data from the study was publicized. This is the first approval of a newly diagnosed glioblastoma therapy since temozolomide was approved in March 2005. Two months later, in December 2015, preliminary results from the EF-14 study were published in the Journal of the American. Medical Association (327). This publication detailed the results for the first 315 enrolled patients, the same patients reported at the 2015 SNO annual meeting. Survival analysis by protocol population (as opposed to intent-to-treat population) provided overall survival from randomization of 20.5 months in the Optune group and 15.6 months for the control group (i.e., approximately 24.3 months and 19.3 months from diagnosis) (hazard ratio = 0.64, p = 0.004).
The results for the entire study population of 695 patients were published in 2016 at the SNO conference, with an updated press release from Novocure in April 2017.
Confirming the results of the interim analysis, the median progression-free survival was significantly improved in the Optune group by just under 3 months (6.7 versus 4 months from randomization). Median overall survival from randomization improved by nearly five months (20.8 versus 16 months). The 2-year survival rate from randomization was 42.5% in the Optune group compared to 30% in the control group. The April 2017 update also reported the 5-year survival rate, which was 13% in the Optune arm versus 5% in the control arm. As of July 2016, the National Comprehensive Cancer Network (NCCN) had assigned the Optune device category 2A in the list of treatments for newly diagnosed glioblastoma, indicating a uniform consensus by the NCCN on the appropriateness of this treatment. Because the NCCN is known for setting standard guidelines for the treatment of cancer in the United States, this has formalized the use of the Optune device as part of a new standard of care for newly diagnosed glioblastoma. Although the Optune device has been incorporated as part of a new standard of care it may still be challenged by some oncologists. Novocure has announced that Optune is now available in over 600 treatment centers in the US (Select this link for a list of centers), and in over 350 other institutions internationally, with offices in Germany, Switzerland, Austria and Japan.
(138) Senior, K. Electrical killing fields for cancer cells. The Lancet Oncology, 2007, 8 (7), page 578.
(327) Stupp, Roger et al. “Maintenance therapy with tumor-treating fields plus temozolomide vs temozolomide alone for glioblastoma: a randomized clinical trial.” Jama 314.23 (2015): 2535-2543.
Good! I hope you enjoyed reading, I have been as faithful as possible. A new chapter very soon!