NovoTTF: where to go from here?

<span class="paragraphSection">Glioblastoma (GBM) remains the most common and aggressive primary brain tumor in adults, and new therapies are desperately needed. Results using a device (NovoTTF, now Optune from Novocure) worn on the head that creates alternating electric fields (tumor treatment fields [TTFs]) in the brain to disrupt mitosis, which was tested in an internationally conducted phase III trial, were presented orally at the 2010 American Society of Clinical Oncology (ASCO) annual meeting and published in manuscript form 2 years later.^{<a href="#CIT0001" class="reflinks">1</a>} In that trial, 237 patients with recurrent GBM were randomized either to "best standard chemotherapy" (BSC) at the physician's discretion (<span style="font-style:italic;">n</span> = 120) or to the device (<span style="font-style:italic;">n</span> = 117). The investigators and sponsor interpreted the results in a favorable manner, concluding that NovoTTF was non-inferior to various chemotherapies with less toxicity.^{<a href="#CIT0001" class="reflinks">1</a>} Various statistical methods were applied in analyzing the data, and controversy ensued, both at the ASCO meeting itself and afterward. Many, including us (T.F.C., A.B.L.), cautioned that it was also possible to interpret the results as demonstrating that: (i) neither TTF nor BSC were particularly effective for recurrent GBM, as the median progression-free survival (about 2 months in both arms) and the 6-month progression-free survival rate (21%, 95% CI: 13.5–29.3 for TTF vs 15%, 95% CI: 7.8–22.3 for BSC, <span style="font-style:italic;">P</span> = .13) were poor and hardly exciting for either treatment; and (ii) failing to improve survival (the primary endpoint of the trial, about 7 mo in both arms, hazard ratio for death with TTF 0.86, 95% CI: 0.66–1.12, <span style="font-style:italic;">P</span> = .27) is not statistically equivalent to affirming non-inferiority.^{<a href="#CIT0001" class="reflinks">1</a>} In our (T.F.C., A.B.L.) experience, nothing much changed in the field, despite FDA approval in 2011. Many interpreted the device as somewhere between a gimmick and a nontoxic placebo. (Of note, while the medical side effects were minimal and quality of life in fact was reported as favorable compared with chemotherapy,^{<a href="#CIT0001" class="reflinks">1</a>} the financial toxicity is not inconsequential.^{<a href="#CIT0002" class="reflinks">2</a>}) Personalized approaches targeting driver mutations continued as investigational drug trials, perhaps now renamed Precision Medicine, and immunotherapy trials blossomed.</span>

http://ift.tt/2qozupw