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Tumor-treating fields extend survival in glioblastoma
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The addition of tumor-treating fields to maintenance temozolomide therapy extended survival among a cohort of patients with glioblastoma, according to results of a randomized phase 3 study.
The regimen — in which a device attached to a patient’s scalp delivers continual doses of low-intensity electric fields — did not negatively affect patients’ quality of life, results showed.
Roger Stupp, MD — professor of medicine (hematology/oncology), neurology and neurological surgery at Northwestern University Feinberg School of Medicine, codirector of Lou & Jean Malnati Brain Tumor Institute in the department of neurological surgery, chief of the division of Neuro-oncology in the department of neurology, and associate director for strategic initiatives at Robert H. Lurie Comprehensive Cancer Center of Northwestern University — and colleagues compared outcomes for 466 patients treated with tumor-treating fields (Optune, Novocure) plus maintenance temozolomide chemotherapy with those for 229 patients who received temozolomide alone.
Results showed patients who received tumor-treating fields achieved longer median OS (20.9 months vs. 16 months; HR = 0.63; P<.001) and median PFS (6.7 months vs. 4 months; HR = 0.63; P<.001).
Adverse event rates appeared comparable between the two study groups.
HemOnc Today spoke with Stupp about the results, their potential implications, the directions that future research will take and the potential that this modality can be effective for malignancies other than brain tumors.
Question: Can you describe the study design ?
Answer: This randomized phase 3 study included 695 patients who completed a 6-week course of radiotherapy and concomitant temozolomide. We randomly assigned patients to maintenance temozolomide and tumor-treating fields or temozolomide alone. PFS and OS served as the main study endpoints.
Q: What did the results show?
A: Patients treated with both temozolomide and tumor-treating fields achieved significantly prolonged PFS and OS, both with risk reductions of 0.63. This is the same magnitude of benefit that we had observed over a decade ago when we introduced temozolomide to the standard of care. This improvement in survival results in a median prolongation of 5 months. At 2 years, 43% of patients who receive tumor-treating fields in addition to temozolomide remain alive, compared with 31% of those who receive temozolomide alone. Importantly, a benefit for tumor-treating fields was seen in all subgroups of patients analyzed, independent of MGMT promoter methylation status, extent of surgery or other factors. A relative benefit also was observed among patients with the worst prognostic factors, including those aged 70 years or older, those with unresected tumors and those with unmethylated MGMT status. We recently reported quality-of-life results. The device did not negatively impact the patients’ quality of life and general well-being; however, as expected, skin irritation from the electrodes and itching have been reported as the main inconvenience. As progression was delayed with the use of tumor-treating fields, a better quality of life was retained for a longer period of time.
Q: Did any of the results surprise you?
A: When embarking on the trial, I was far from sure that this novel treatment was going to impact the outcome and growth of this disease in a substantial manner. Too often we are unable to translate the preclinical and animal findings and results into a meaningful therapy for our patients. I am happy to see that we now have an additional arm in the fight against this most aggressive form of a primary brain tumor.
Q: How have these findings impacted clinical practice, and what still must be confirmed in subsequent research?
A: This has immediately impacted my daily practice and the practice of many colleagues. Every patient gets informed about this innovative form of cancer therapy, which is yet another step toward ultimately curing this disease. As is true with all the treatments we have available, there is a lot more to learn and to improve on. Ongoing trials will determine whether tumor-treating fields as a modality has any effect and benefit in tumors other than brain cancer. Research is ongoing to look at why and how tumors escape the tumor-treating fields therapy. And can we identify biomarkers or characteristics of the tumors that are most susceptible to tumor-treating fields.
Q: W hat questions still need to be addressed in terms of efficacy and safety?
A: Clearly, we wish to investigate the effect and benefit of tumor-treating fields on brain tumors other than glioblastoma. With regard to safety, the device is safe and well tolerated overall. Nevertheless, skin reactions, itching under the electrodes or occasional skin lesions requiring treatment interruptions may cause a challenge. As we expand our experience, we learn to administer better local care, possibly with the use of topical antibiotics or steroids. Over time, modern technology will also allow for further miniaturization. The bulk of the weight of the device is its power source: the batteries. Now that we even build race cars on batteries, the batteries for the device will become smaller over time. Just remember the first cell phones or computers.
Q: Do you expect tumor-treating fields will have utility in other malignancies?
A: Yes, ongoing trials are being conducted in pancreas cancer, mesothelioma, lung cancer and brain metastases. For some indications, I am a little more skeptical, while for tumors that have primarily a loco-regional growth, this approach may truly be a game changer. One of the advantages of this approach is that it can easily and without overlapping toxicity be combined with other systemic therapies, such as chemotherapy or immunotherapy. – by Rob Volansky
References:
Stupp R, et al. JAMA. 2017;doi:10.1001/jama.2017.18718.
Taphoorn M, et al. JAMA Oncol. 2018;doi: 10.1001/jamaoncol.2017.5082.
For more information:
Roger Stupp, MD, can be reached at Northwestern Medicine, 676 N. St. Clair St., Suite 2210, Chicago, IL 60611; email: roger.stupp@northwestern.edu.
Disclosure: Stupp served as principal investigator of two Novocure-sponsored clinical trials with tumor-treating fields for recurrent and newly diagnosed glioblastoma. He received travel support when presenting the trial design or results at scientific meetings. He served as an informal adviser to Novocure for these research protocols (nonremunerated). He also has served on advisory boards for AbbVie, Celgene and EMD Serono (Merck Darmstadt), and received honoraria when applicable to the institution. His spouse is a full-time employee of Novartis.