Optune Pax Lays the Foundation for Future TTField Development in Locally Advanced Pancreatic Cancer

The FDA approval of Optune Pax, a first-of-its-kind, portable, and noninvasive device, for concomitant use with gemcitabine and nab-paclitaxel (Abraxane) for locally advanced pancreatic cancer not only marked the first new treatment modality approved for this indication in nearly 30 years but also serves as proof-of-concept for device-based, multimodal therapy in a disease defined by its resistance to systemic treatment, according to Vincent Picozzi, MD.¹

Data from the phase 3 PANOVA-3 trial (NCT03377491), which supported this regulatory decision, showed that adding Optune Pax to the control regimen significantly improved overall survival (OS; HR, 0.82; 95% CI, 0.68-0.99; P = .039) and extended the median time to pain progression to 15.2 months (95% CI, 10.3-22.8) from 9.1 months (95% CI, 7.4-12.7) with gemcitabine and nab-paclitaxel alone.^1,2 In regards to safety, device-related skin adverse effects (AEs) occurred in 76.3% of patients, the majority of which were low grade.²

“These results, although impressive unto themselves, really just represent a foundation for further exploration of the use of the device in combination with other therapies in pancreatic cancer,” Picozzi, a medical oncologist and director for the Pancreaticobiliary Program at the Floyd & Delores Jones Cancer Institute at Virginia Mason Medical Center in Seattle, Washington, stated in an interview with OncLive®.

During the interview, Picozzi detailed the biologic rationale underlying tumor-treating fields (TTFields) like Optune Pax; reviewed practical considerations for patient selection and proactive management of device-related skin AEs in routine clinical use; and discussed how TTFields may be integrated into an evolving pancreatic cancer treatment landscape.

OncLive: For those who may be less familiar with this technology, what is the biologic rationale behind TTFields? How do they work, and what makes their mechanism particularly complementary to chemotherapy in pancreatic cancer?

Picozzi: TTFields are alternating electrical fields that are passed through the cancer site. The initial and primary thought [behind this technology] is that because pancreatic cancer cells have a polarity, you can disrupt the assemblage of the apparatus that leads to cell division through the alternation of the electrical fields. The basic mechanism is that the device prevents cells from dividing and therefore growing, but there are a variety of additional effects that occur, which include changes in the biology of the cancer, including its ability to migrate and spread. It also appears that by doing this, an immunological effect is generated by the host against the cancer. There are a variety of mechanisms whereby pancreatic cancer becomes more susceptible to treatment because of TTFields.

What were some of the early data with Optune Pax in other tumor types that led to its evaluation in pancreatic cancer?

The use of TTFields in glioblastoma seemed to produce a survival advantage in a cancer that's very difficult to manage. The [drug’s developer, Novocure] then went on and tested the approach in mesothelioma and lung cancer, and pancreatic cancer was a target based on its refractory nature to standard therapy. That's what led to the exploration of these devices in conjunction with chemotherapy in cancers that were localized to the pancreas but not generally operable.

What efficacy and quality of life (QOL) findings from PANOVA-3 supported the regimen’s approval, and how clinically meaningful were these results?

There was a statistically significant improvement in OS, something that has really not been seen in general in studies involving locally advanced pancreatic cancer. Coupled with that, not only was there improvement in quantity of life, but QOL, most particularly pain control. This is especially important to patients. Pain is the primary symptom they're concerned about, and because we're dealing with a disease that is not curable, QOL takes on a special importance. The toxicity from the use of the device itself was readily manageable. It was pretty much limited to skin toxicity, which can be approached in a variety of ways, although there were a small fraction of patients that could not use the device.

Given the combination of improvement in survival quantitatively, improvement in survival qualitatively, and the ability of patients to tolerate the treatment both with respect to usage and side effects, [the FDA approved the device].

As TTFields move into routine practice, what are some proactive strategies to help prevent, recognize, and manage known toxicities?

Really, the only incremental AE from the use of the device is skin toxicity, which can take on a variety of forms. [Novocure] has done a good job trying to understand what these skin toxicities are and how to manage them. There are several publications pending in the literature concerning this, and very specific guidance exists in terms of not just treatment but prevention. It is something that treating physicians, particularly oncologists, need to familiarize themselves with, along with their staff and patients. If the appropriate preventive steps are used and appropriate intervention is used at the outset of issues, then it really becomes a manageable concern for most people.

In which clinical scenarios would you recommend vs not recommend using Optune Pax?

There are 3 things to consider [when thinking about patient selection for Optune Pax]: stage of disease, type of chemotherapy, and practicality of use. Number one, the device is approved for locally advanced pancreatic cancer, although it appears to have activity against pancreatic cancer not just in the primary site but in metastatic sites as well. Number two, patients [need to be able to] receive gemcitabine and nab-paclitaxel. The third consideration is a patient who is willing to use the device for the time required, which is a number of hours each day that can seem burdensome. In point of fact, in the PANOVA-3 trial, most people were able to use the device for the requisite time. The average time on device was 15 hours per day that people were able to achieve, and Novocure has a wonderful support staff that really helps patients with the logistics and practicalities of using the device. With that resource, being able to use the device is something that most people can accomplish.

What results are we seeing from PANOVA-4 (NCT06390059), the phase 2 trial evaluating TTFields in metastatic pancreatic cancer?³

The results in this patient population were encouraging with respect to the use of TTFields in metastatic disease, but it was not a randomized trial. We are also at a time in which treatment for advanced pancreatic cancer is rapidly changing; the introduction of KRAS inhibition is going to completely change the paradigm of treatment in advanced pancreatic cancer. So how the use of TTFields fits into this new milieu, in which KRAS inhibitors, to my mind, become the new cornerstone of treatment, is more speculative and yet to be seen. But it is certainly something to think about, because of the systemic effect and the overall favorable results. [Novocure is] deliberating its next steps, based on the success of PANOVA-3 and to a lesser extent PANOVA-4.

Given that Optune Pax introduces an entirely new modality into pancreatic cancer management, how do you envision it being integrated into the broader treatment paradigm, and what questions remain regarding its use?

In terms of current usage, there remain questions as to whether it can be effectively used with alternative chemotherapy such as the FOLFIRINOX regimen and how much we have to use the device in terms of hours per day and days within our treatment sequence. That aspect is yet to be fully clarified.

I view [these data] as foundational and can see a variety of ways in which the device could be expanded in this general area of oncology. Because survival in pancreatic cancer is generally controlled by preventing spread throughout the body, looking at the device with other therapies—both standard and emerging—is very attractive. Fortunately, we're at a period in pancreatic cancer where there is a whole host of new therapies, beginning with KRAS inhibitors that are being developed. Secondly, there would be interest in how the device would combine with other local therapies, of which various forms of radiation therapy would be an obvious consideration, along with other forms of local therapies being developed. Thirdly, one could envision expanding the use of the device to other stages of pancreatic cancer and even other cancers with similar biology. For example, patients who have localized disease that may not be quite as advanced as those with locally advanced pancreatic cancer could, in theory, benefit from this. The use in the metastatic setting in certain situations would also seem appealing, as would other cancers with similar anatomy and biology, such as biliary cancer, ampullary cancer, and duodenal cancer.

References

1. FDA approves first-of-its-kind device to treat pancreatic cancer. FDA. February 12, 2026. Accessed June 11, 2026. https://www.fda.gov/news-events/press-announcements/fda-approves-first-its-kind-device-treat-pancreatic-cancer
2. US FDA approves Novocure’s Optune Pax for the treatment of locally advanced pancreatic cancer. News release. Novocure. February 11, 2026. Accessed June 11, 2026. https://www.novocure.com/us-fda-approves-novocures-optune-paxr-treatment-locally-advanced-pancreatic-cancer
3. EF-39 PANOVA-4: study of tumor treating fields concomitant with atezolizumab, gemcitabine and nab-paclitaxel as first-line treatment for metastatic pancreatic ductal adenocarcinoma. ClinicalTrials.gov. Updated April 30, 2025. Accessed June 11, 2026. https://clinicaltrials.gov/study/NCT06390059