The use of tumor treating fields (TTFields) as a treatment for patients with brain tumors has, thus far, largely been focused on in glioblastoma, but an upcoming trial aims to expand the use of the device to the grade III patient population, says Daniel O’Connell, MD.

Currently, the device is only FDA approved for use in grade IV brain tumors, but O’Connell, a neuro-oncologist at UCLA’s David Geffen School of Medicine, anticipates the FDA will grant its approval for use in grade III tumors within the next 2 to 3 months.

, O’Connell discusses the upcoming trial, which will test the efficacy of TTFields in these patients, as well as the impact the device has already made in the grade IV patient population.

 What impact have TTFields made so far in brain cancer, and what do you envision the future use will be?

The first trial in humans for TTFields in the brain tumor community was for glioblastoma, and the focus has thus far been largely on glioblastoma, for obvious reasons. Glioblastoma carries the most devastating prognosis, median survival times are the shortest, and it is the highest-grade glioma. Therefore, the focus has been on that.

Increasingly, there has been a buildup of evidence in favor of the use of TTFields in improving the side effect profile relative to standard chemotherapies, or at least not making it worse. With regards to outcomes such as survival times, there has increasingly been more evidence mounting in favor of prolonged survival with the device. However, this has not been used beyond the grade IV domain. I did see some additional posters at this meeting regarding the use of TTFields in meningioma, and I know in the lung cancer world there are some works in progress regarding TTFields. However, for the grade III tumors, that is our focus.

Currently, this device is only FDA approved for grade IV tumors, so we anticipate the FDA approval for the device for grade III tumors in the next 2 to 3 months—I can’t see a reason why this would not go through. And then we will obtain approval to finally start enrolling patients in the trial, which we have received funding for. It is a phase II study demonstrating the use of TTFields in grade III anaplastic astrocytoma population.

Great question. It’s going to be some time, because the grade III patients have a better prognosis; they live longer. Proportionally, there are fewer of them. There are proportionally more glioblastoma patients amongst the patients with glioma. There is not as big of a patient population.

Our catchment area is within Southern California—Orange County community hospitals, and we hope to recruit folks in LA County, as well. Our minimum goal of recruitment is 26 patients, with up to 36 allotted. We anticipate this trial lasting years, because these patients, regardless of therapies, typically live a median survival of 5 to 9 years. The use of this will hopefully push us over to that 9-year mark and beyond&mdash;that’s our hope, of course, for these patients. So this will be a long-standing trial running through, I anticipate, 2018, 2019, 2020. It will take some time.

Is this trial a next step to the EF-14 trial?

You can view this trial as an additional step moving beyond the EF-14 trial, which is quite a landmark trial. Finally, we’re seeing a significant difference on multiple levels for the Optune device for TTFields.

We started with EF-11, which demonstrated against physician’s choice chemotherapy and TTFields that TTFields provide the same overall benefit in addition to not having the side effects of chemotherapy. EF-14 has now demonstrated that, in tandem with the chemotherapy, that patients do better with the TTFields clearly, and this is also stratified by subgroups and hazard ratios, etc.

Our plan is to take this another step, as it appears some other folks are actively pursuing, and extending it to the grade III patients. Who’s to say that there may be an even more demonstrable benefit in the grade III population. It will take a lot of time to tell. It takes time for the TTFields to work in and of themselves—a couple months, so in order to see that result, you have to start earlier rather than later, which is our goal to help offset and utilize the cytostatic mechanism of TTFields to prevent the cell population from further dividing tumor cells.

What impact could this device have for patients?

One of the big questions we get in our clinic at UCLA is, what other modalities can be used to help offset the devastating nature of glioma, particularly glioblastoma? Increasingly, our grade III patients, our young grade III patients, are curious as well. They go online and look and see what the average prognosis, etc. is for patients with their diagnosis. They want to know what else can be done. This is a different modality than immunotherapy, targeted therapy, and traditional chemotherapy, in that it utilizes a novel mechanism. It is not ionizing radiation, it is distinct from radiation therapy, although sometimes comparisons are made from a trial standpoint. It’s different, and it can be used differently.

There is also interest in attempting to use TTFields with radiation therapy, which initiates usually for most patients shortly after resection (should they have a resection; most do). In order to push it back further, and that would apply not only to the glioblastoma patients, for which the EF-11 and EF-14 trials have been designed and used for, but also for our patient population that we’re interested in—the grade III&mdash;to see if it can start early. Believe it or not, there are quite a few patients that are very proactive, that even with a prognosis that is fairly good compared with the glioblastoma group, still want everything done, understandably. They’re looking into the future and they want to do something as soon as possible. This is a mechanism of action that can be used for them.

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An upcoming study hopes to expand the use of tumor treating fields (TTFields) from only glioblastoma (grade IV tumors) into also treating grade III anaplastic astrocytomas as well.

Potential Expansion for TTFields into Treating Grade III Brain Tumors

Patients with metastatic colorectal cancer (mCRC) who engaged in daily moderate physical activity demonstrated a reduction in mortality and cancer progression, according to the results of a new analysis, which will be presented at the upcoming 2017 Gastrointestinal Cancer Symposium in San Francisco, CA.

Though previous studies have shown a link between exercise and improved outcomes in early-stage CRC, this is the first evidence to show this association in patients with non-local metastases.

The prospective cohort study nested within the National Cancer Institute (NCI)-sponsored randomized Alliance control trial included 1,231 patients with mCRC who received chemotherapy and self-reported their physical activity via a questionnaire. Researchers then determined each patient’s level of activity based on metabolic equivalent task (MET)-hours per week, which assesses energy expended during physical activity.

Overall, the patients who spent more time participating in moderate physical activities such as walking, cleaning, or gardening had reduced rates of cancer progression and death. Patients who reported an engagement in physical activity equivalent to 30 or more minutes of moderate exercise daily, or 18 or more MET-hours per week, experienced an overall survival (OS) rate of 0.81 (95% CI 0.67 to 0.98, 

 for trend 0.03), which represented a 19% reduction in mortality, and a progression-free survival (PFS) of 0.84 (95% CI 0.71 to 1.00, P for trend 0.03), which represented a 16% reduction in cancer progression.

The study also found that patients who spent 5 or more hours per week doing non-vigorous activity, such as walking or yoga, had a 25% reduction in mortality. However, there was no association found between vigorous activity, such as running or playing sports, and cancer outcomes.

“Patients should know that even as little as 30 minutes of moderate activity per day may improve outcomes for colorectal cancer patients,” said lead study author Brendan Guercio, MD, Brigham and Women’s Hospital.

Guercio said these findings suggest that even light activities, which many patients with mCRC may be able to participate in, can be associated with improved outcomes.

The most important question to address regarding the findings of the study was the role of confounders, Guercio said.

“In other words, the question was: is physical activity making people healthier, or were individuals who were sicker than others just exercising less?” he said.

To address this issue, regression analyses were used to calculate hazard ratios for disease progression and mortality for levels of self-reported physical activity after adjusting for potential confounders, including comorbidities, weight change over the prior 6 months, ECOG performance status, body mass index, chemotherapy received, tumor KRAS status, gender, and age.

Randomized controlled trials and more prospective clinical studies are needed to confirm the link between physical activity and outcomes in mCRC. A randomized clinical trial is currently ongoing to compare patients who exercise during treatment with those who do not, with the hope of confirming the impact of physical activity on cancer outcomes.

 Guercio BJ, Venook AP, Niedzwiecki D, et al. Associations of physical activity with survival and progression in metastatic colorectal cancer: Results from CALGB 80405 (Alliance). Abstract presented at: 2017 Gastrointestinal Cancers Symposium; January 19-21, 2016; San Francisco, CA. Abstract 659.

According to new analysis, patients with metastatic colorectal cancer (mCRC) who engaged in daily exercise demonstrated improved outcomes.

Shannon Connelly

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Potential Expansion for TTFields into Treating Grade III Brain Tumors

Daily Exercise May Improve Survival for Patients with mCRC