How Is Optune Pax Reshaping Locally Advanced Pancreatic Cancer Care?

With the introduction of Optune Pax to the pancreatic cancer treatment paradigm, the clinical role of tumor treating fields (TTFields) may extend beyond use with gemcitabine plus nab-paclitaxel (Abraxane)–based regimens, and future research with this treatment modality may provide clarity on open questions, including this modality’s unexpected effect on distant progression-free survival (PFS), potential synergy with immunotherapy, and the potential ability to improve resectability, according to Andrew H. Ko, MD.

In February 2026, the FDA approved the TTFields device Optune Pax for concomitant use with gemcitabine and nab-paclitaxel for the treatment of adult patients with locally advanced pancreatic cancer, based on data from the PANOVA-3 trial (NCT03377491).¹

“We’re in an exciting and transformative time in pancreas cancer regarding systemic therapies with RAS inhibitors, etc.” Ko said in an interview with OncLive®. “The whole field is changing, and in the context of drugs that are going to help patients optimistically live a lot longer, will the benefits of TTFields be accentuated, or perhaps contracted with more effective systemic therapies? That remains an open question.”

As Ko alluded to, TTFields has entered a pancreatic cancer treatment paradigm that is already growing more robust with the potential of agents like the oral RAS(ON) multiselective inhibitor daraxonrasib (RMC-6236), which is under FDA review for approval for the treatment of patients with previously treated metastatic pancreatic ductal adenocarcinoma, based on findings from the phase 3 RASolute 302 trial (NCT06625320).²

In the interview, Ko discussed how TTFields treatment works, early data that supported the PANOVA-3 trial investigating Optune Pax in patients with pancreatic cancer, key data from PANOVA-3, and the potential for evaluating TTFields in combination with other therapies.

Ko is an associate professor of medicine in the Division of Hematology/Oncology in the Department of Medicine and is part of the Surgical Oncology Program in the Department of Surgery at the University of California San Francisco Comprehensive Cancer Center.

OncLive: What is the biologic rationale behind TTFields? How does this therapy work, and what makes its mechanism of action complementary to chemotherapy in pancreatic cancer?

Ko: As opposed to drug therapy, TTFields is a wearable device that patients with locally advanced pancreatic cancer can use. It delivers low-intensity electric fields to the tumor, and this disrupts normal cellular mechanisms that are responsible for tumor survival, growth, and progression. It’s an external wearable device that can help shut off cell signaling and improve outcomes for patients with locally advanced pancreas cancer.

What early findings with Optune Pax in other tumor types like glioblastoma and mesothelioma supported its evaluation in pancreatic cancer?

Its original approval was for patients with glioblastoma. My colleagues in neuro-oncology use it in select patients. For brain tumors, the device is worn on the head. Subsequent evidence [has shown] that this approach, in terms of delivering these electric fields, can improve outcomes in patients with mesothelioma and even lung cancer. We’re seeing [its use in] a broader range of solid tumor indications, and now with its positive data from PANOVA-3 in locally advanced pancreas cancer, we’re seeing a proof of principle regarding the benefits of this approach.

What efficacy and QOL findings from PANOVA-3 supported the FDA approval of Optune Pax?

PANOVA-3 was for patients with locally advanced—unresectable but nonmetastatic—disease. The study was a randomized trial in which patients with locally advanced pancreas cancer were randomly assigned to receive chemotherapy [in the form of] gemcitabine plus nab-paclitaxel, which is a common frontline standard regimen for pancreas cancer, with or without the use of TTFields. This study, which enrolled 571 patients, showed that overall survival [OS] was significantly improved with the combination of chemotherapy and TTFields. [HR, 0.82; 95% CI, 0.68-0.99; log rank P = .039], and there was an incremental improvement in median OS by 2 months with the addition of TTFields to chemotherapy.³

However, there were a couple other important clinical outcomes that also showed a benefit. The most notable one [related to] quality of life [QOL] was prolongation of pain-free survival. There was a bit more of a substantial improvement in pain-free survival in patients wearing TTFields, which is a clinically meaningful outcome for from a QOL standpoint for patients with advanced pancreas cancer.

What is the safety profile of Optune Pax, and how might its home-based delivery help address existing gaps and unmet needs in pancreatic cancer care?

In the study as a whole, the toxicities were primarily related to chemotherapy, [such as] cytopenias. However, specific to TTFields, [we saw] primarily skin [toxicities, including] dermatitis and irritation at the site where the device is worn; these were generally mild, though. In total, 7.7% of patients had grade 3 adverse effects [AEs] related to TTFields, but most of these AEs were in the realm of mild irritation and local effects, nothing that represents a dealbreaker.³ Patients have to wear this device for, ideally, at least 14 to 16 hours a day, so there is that logistic and slightly cumbersome aspect to it, but I’d say with a positive trade-off and with manageable and generally mild device-related AEs.

Now that Optune Pax has been FDA approved and is being used in clinical practice, in which scenarios would you recommend using this therapy?

It warrants a discussion with any patient with locally advanced pancreas cancer. We need to share the positive data with patients, including the modest improvement in OS but perhaps of equal or greater importance, the improvement in pain-free survival. The PANOVA-3 study was specific for patients receiving gemcitabine and nab-paclitaxel, but I would find it hard to believe that this is a chemotherapy agent–specific phenomenon. It’s fair to extrapolate to use TTFields in the patients in whom we often use FOLFIRINOX [leucovorin, 5-fluorouracil, and irinotecan] as an alternative regimen.

How might the continued introduction of TTFields contribute to adjustments in multimodal management strategies for the pancreatic cancer treatment paradigm?

It warrants further study beyond [its use] with conventional chemotherapies. Whether it can increase the rate of resectability for patients with borderline resectable and locally advanced tumors might come into play.

One interesting finding from the PANOVA-3 study that I didn’t expect is that we think of TTFields as a local treatment, but it also improved the rates of distant disease, meaning distant PFS. Somehow, a local treatment might reduce or prolong the time from development of distant metastases. We don’t [typically] see a local treatment having an effect on preventing or delaying the development of distant metastases. That’s worth noting. If there’s any possible synergy or effect on the immune system, that might indicate ways of combining [TTFields] with immunotherapy, for example. These are potential avenues for further exploration in the future.

What does the future look like for investigating TTFields in pancreatic cancer?

This is being evaluated for locally advanced disease, but is there a role for this even in the metastatic setting? My initial instinct would have been no, but a putatively local approach may still have benefits in the more systemic or metastatic setting. There are going to be trade-offs. Is this going to be appropriate for every patient, or are there select patients this is going to be particularly beneficial for? Is it going to be more beneficial with select types of systemic therapies? I don’t know the answer to all these questions, but these are what can be spurred from these promising results from PANOVA-3.

References

1. FDA approves first-of-its-kind device to treat pancreatic cancer. News release. FDA. February 12, 2026. Accessed July 31, 2026. https://www.fda.gov/news-events/press-announcements/fda-approves-first-its-kind-device-treat-pancreatic-cancer
2. Revolution Medicines’ new drug application for daraxonrasib accepted for review by U.S. FDA for previously treated metastatic pancreatic cancer. News release. Revolution Medicines. July 22, 2026. Accessed July 23, 2026. https://ir.revmed.com/news-releases/news-release-details/revolution-medicines-new-drug-application-daraxonrasib-accepted
3. Babiker HM, Picozzi V, Chandana SR, et al. Tumor treating fields with gemcitabine and nab-paclitaxel for locally advanced pancreatic adenocarcinoma: randomized, open-label, pivotal phase III PANOVA-3 study. J Clin Oncol. 2025;43(21):2350-2360. doi:10.1200/JCO-25-00746