Landmark FDA Approval of Optune Pax Signals Broader Shift Towards Multimodal Therapies in the Pancreatic Cancer Paradigm

As the first positive trial for tumor-treating fields (TTFields) in locally advanced pancreatic cancer, the pivotal phase 3 PANOVA-3 study (NCT03377491) not only supports the addition of Optune Pax to the treatment armamentarium, but establishes a strong foundation for the continued development of device-based, multimodal treatment in this disease setting, according to Vincent Picozzi, MD.

Data from PANOVA-3 supported the February 2026 FDA approval of this first-of-its-kind, portable, and noninvasive device for concomitant use with gemcitabine and nab-paclitaxel (Abraxane) in adult patients with locally advanced pancreatic cancer.^1,2 In this study, 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.

“I see these results as foundational, not final,” Picozzi stated in an interview with OncLive®. “The device works in a fundamentally different way, so there’s going to be further opportunity for clinical advances as we grow to understand the true efficacy of the [device], its mechanism, and how it can synergize with other agents.”

During the interview, Picozzi detailed what sets Optune Pax apart from available systemic therapies; expanded on the magnitude and clinical relevance of the OS and quality-of-life (QOL) benefits observed in PANOVA-3; and spotlighted additional ongoing evaluations of this device in combination with immunotherapy in metastatic pancreatic cancer.

Picozzi is a medical oncologist and director for the Pancreaticobiliary Program at the Floyd & Delores Jones Cancer Institute at Virginia Mason Medical Center in Seattle, Washington.

OncLive: As a first-in-class approach for pancreatic cancer, how does the mechanism of action for Optune Pax differ from standard systemic therapies?

Picozzi: [This device] works in a completely different way, by passing alternating electrical fields through the tumor. The primary mechanism of action was thought to be to disrupt the cellular mechanism by which cells divide. However, it turns out that in the course of doing that, there may be other mechanisms that exist, including an immunogenic effect, that can also have an effect on the cancer. We’re still learning exactly how TTFields work.

What were some of the clinical and QOL benefits observed with Optune Pax in PANOVA-3?

The biggest thing is a 2-month prolongation of OS in patients [treated with Optune Pax] in the intention-to-treat [ITT] population; [this increase was] even bigger in the modified ITT population.^1,2 Coupled with that, there were significant improvements seen in QOL parameters as formally measured in virtually all domains. QOL is also important, and in some cases is more important to these patients than quantity of life, given that, in general, locally advanced pancreatic cancer is not curable. The most important [QOL improvement] was a delay in the progression of pain by almost 7 months using this device vs the control. I personally regard pain as probably the most important symptom to palliate and the most important aspect of QOL. [Taken together], these improvements in both quantity and QOL are what led to the [device’s] FDA approval.

Given the historically limited progress in locally advanced pancreatic cancer, why is the approval of Optune Pax particularly significant, and what avenues for future investigation does PANOVA-3 open up?

The PANOVA-3 trial, in which the TTFields were tested, is really the first positive trial ever in this stage of pancreatic cancer. It’s a historical landmark for that reason, and it currently offers an advantage to that specific patient population.

[Of note, the drug’s developer], NovoCure, is currently conducting a [phase 2] trial called PANOVA-4 [NCT06390059], which [is evaluating] the device in combination with [atezolizumab (Tecentriq), nab-paclitaxel, and gemcitabine] in metastatic pancreatic ductal adenocarcinoma.³ That study will be of great interest, particularly because one of the findings from PANOVA-3, somewhat surprisingly, was that systemic disease progression was also improved with the use of the device. It appears it may have a systemic effect as well as a local effect relating to its immunological mechanism.

Additionally, there is the potential for the device to combine with many other treatments, such as chemotherapy, KRAS inhibitors, PARP inhibitors, and immunotherapy. The [device’s mechanism of action], as it’s [currently] understood, interfaces well with many of the evolving treatment modalities for pancreatic cancer.

What is the safety profile of this wearable device, and how does its home-based delivery address existing gaps in pancreatic cancer care for patients?

The device itself is quite safe. There really were no additive systemic adverse effects [AEs] from using it [in combination] with chemotherapy. The major AE from the device itself is skin toxicity, which can range from very mild to much more severe. Between 5% and 10% of patients in the initial testing had skin reactions such that they could not continue using the device; however, with time and learnings about supportive care, my expectation is that number will diminish. A big advantage is that it doesn’t add to the systemic toxicity of chemotherapy.

In terms of being able to use this device at home, that is always tremendously valued by patients. If we contrast [this device] with radiation therapy, in which patients have to travel to a radiation facility daily, sometimes for a number of weeks, [Optune Pax] becomes a much more convenient therapy. It is one that interfaces better with chemotherapy and has fewer AEs. Additionally, NovoCure has a very vigorous and effective support team that helps people with the device in their home in terms of maintenance, any problems that arise, and guidance. This makes it easy for the patients to use this device at home.

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

Under the current guidance, [Optune Pax] can be applied to patients with locally advanced pancreatic cancer almost irrespective of their circumstances. If we think about who this might not be the best option for, there are certainly patients who will not tolerate wearing the device for the time required. Currently, the guidance [for treatment administration] is 16 hours per day, so there is a practical factor there. Other examples include [patients] who have had recent abdominal trauma or surgery, or [those] who have other skin conditions. [These are some] patient populations for which this becomes more cumbersome.

References

1. FDA approves first-of-its-kind device to treat pancreatic cancer. News release. FDA. February 12, 2026. Accessed March 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 March 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 March 11, 2026. https://clinicaltrials.gov/study/NCT06390059