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Optune Pax to treat locally advanced pancreatic cancer

Author: Grace Stroman

Editor: Meghan Diefenbacher

Today’s article will discuss the Food and Drug Administration (FDA) approval of Optune Pax® for pancreatic cancer as a result of the PANOVA-3 study. On February 11th, 2026, Optune Pax in combination with gemcitabine and nab-paclitaxel chemotherapy was approved for adults with unresectable locally advanced pancreatic adenocarcinoma.1 It represents the first FDA approval for this indication in nearly 30 years. The primary endpoint of the global PANOVA-3 trial was overall survival (OS) and the secondary endpoints were overall response rate (ORR), progression-free survival (PFS), pain-free survival, tumor resectability rate, and puncture-free survival.2 Developed by Novocure, Optune Pax is a wearable medical device that generates low, alternating electric tumor treating fields (TTFields) which interfere with tumor proliferation.

Key points

  • Novocure’s Optune Pax is a noninvasive medical device that locally delivers customizable low frequency alternating electric fields
  • The PANOVA-3 phase III study indicated TTFields are safe and provide superior median OS for adults with unresectable pancreatic adenocarcinoma
  • TTFields prolonged patient 1-year survival rate, 1-year PFS rate, length of pain-free survival, and time to distant PFS

What is pancreatic cancer?

In 2025, pancreatic cancer accounted for 8% of cancer deaths in the United States and is the fourth and third leading cause of cancer deaths for men and women, respectively.3 This is due to the poor 5-year survival rate of ~13%, lack of optimal screening tools for early diagnosis, and difficulty identifying high-risk populations for screening.4-5 Pancreatic ductal adenocarcinoma represents ~80% of all pancreatic cancer cases with pancreatic neuroendocrine tumours and neuroendocrine carcinomas being the next most common.4 Over 80% of cases arise sporadically due to somatic mutations and familial pancreatic cancer accounts for 4-10% of cases.4 Risk factors for sporadic pancreatic cancer are age, chronic pancreatitis, tobacco use, Helicobacter pylori infection, and dietary habits.4 For unresectable locally advanced pancreatic adenocarcinoma patients in the PANOVA-3 trial, the standard of care is neoadjuvant chemotherapy cocktails (e.g.. gemcitabine and nab-paclitaxel) followed by surgery based on tumor shrinkage.4,6 The gemcitabine and nab-paclitaxel cocktail was shown to increase median OS and PFS by 1.8 months compared to gemcitabine alone.7

TTFields established preclinical and clinical findings

TTFields therapy uses low frequency (100-300 kHz) alternating electric fields to disrupt cellular properties. In preclinical models, this approach was originally shown to affect actively proliferating cancer cells and slow in vivo tumor growth. By interfering with electrical forces required for chromosome alignment during mitosis, TTFields therapy halts cell proliferation and disintegrates diving cells.8 Further studies have shown that TTFields induce DNA damage, replication stress, and endoplasmic reticulum stress.9-11 These forms of cellular distress can stimulate innate and adaptive immune-mediated cell death, enhance anti-PD-L1 (Programmed Death-Ligand 1) efficacy, and tumoral immune cell infiltration.11-13 Using a preclinical pancreatic cancer model, Giladi and colleagues demonstrated enhanced TTFields efficacy when combined with gemcitabine and fluorouracil which function as DNA and nucleotide synthesis chemotherapeutic inhibitors.14 These preclinical findings have translated into the clinical setting. Novocure’s non-invasive, wearable NovoTTF-200T System TTFields therapy device is now FDA approved for glioblastoma, non-small cell lung cancer, and mesothelioma.15-17 

PANOVA-3 study design and results

The PANOVA-3 was a global, randomized, open-label phase III trial designed to access the safety and efficacy of TTFields with gemcitabine and nab-paclitaxel as first-line therapy for adults with locally advanced pancreatic adenocarcinoma (Figure 1).2 The multicenter study recruited 571 patients spanning 196 sites representing 20 countries. Patients were randomized 1:1 to receive TTFields with gemcitabine and nab-paclitaxel or gemcitabine and nab-paclitaxel alone. Novocure’s NovoTTF-200T System delivered 150 kHz TTFields with a recommended usage of ≥18 hours per day. Gemcitabine and nab-paclitaxel were infused once per day on days 1, 8, and 15 of a 28-day cycle. Patients were monitored during follow-up visits every 4 weeks and imaging was performed every 8 weeks to assess response. Treatment was terminated upon disease progression as defined by RECIST v1.1, adverse toxicity, pregnancy, consent withdrawal, or a break in compliance.

Figure 1: The PANOVA-3 study was designed as a randomized, multisite, open-label phase III trial to measure the safety and efficacy of TTFields in locally advanced pancreatic adenocarcinoma. Patients were randomized 1:1 to receive TTFields alongside chemotherapy or chemotherapy alone. Created in BioRender. Stroman, G. (2026) https://BioRender.com/975rowi

The PANOVA-3 trial reached its primary and secondary endpoints and Optune Pax was well tolerated. As the primary endpoint, the combination of TTFields, gemcitabine, and nab-paclitaxel significantly (P = 0.039) extended median patient OS to 16.2 months (95% CI, 15.0 to 18.0) compared to 14.2 months (95% CI, 12.8 to 15.4) with gemcitabine, and nab-paclitaxel treatment. TTFields therapy significantly prolonged patient 1-year survival rate (68.1% v. 60.2%), 1-year PFS rate (43.9% v. 34.1%), length of pain-free survival (15.2 v. 9.1 months), and time to distant PFS (13.9 v. 11.5 months). Other secondary endpoints including overall PFS, local PFS, ORR, tumor resectability rate, and puncture-free survival were not significantly improved with TTFields therapy. The majority of TTFields adverse events (AEs) reported were mild-to-moderate dermatological reactions to the device with 7.7% of patients experiencing ≥3 grade skin events. AEs led to 15.8% of patients discontinuing chemotherapy while AEs led to 8.4% of TTFields patients discontinuing. Finally, four patients (0.7%) died from chemotherapy-related AEs, but no patient succumbed to TTFields AEs. The PANOVA-3 study is a milestone as it represents the newest FDA approval available for patients in nearly 30 years and offers an additional few months of reduced pain for an already dismal disease outlook.

Looking ahead

Novocure’s TTFields technology is expanding into additional clinical combinatorial studies and indications. The PANOVA-4 phase II study is testing first-line TTFields with gemcitabine, nab-pactitaxel, and the PD-L1 inhibitor atezolizumab for metastatic pancreatic adenocarcinoma.18 For metastatic non-small cell lung cancer, the LUNAR-2 and LUNAR-4 studies are evaluating the safety and efficacy of TTFields with the PD-1 inhibitor pembrolizumab and platinum-based chemotherapy as first- and second-line treatment options, respectively.19-20 For glioblastoma patients, the KEYNOTE D58 and TRIDENT studies are investigating the use of TTFields and temozolomide chemotherapy with pembrolizumab or radiation, respectively.11-22 These ongoing studies will continue to determine the safety and efficacy of TTFields in new indications and test the clinical translatability of this new technology.

References 

  1. NovoCure Ltd. Pivotal, Randomized, Open-Label Study of Tumor Treating Fields (TTFields, 150kHz) Concomitant With Gemcitabine and Nab-Paclitaxel for Front-Line Treatment of Locally-Advanced Pancreatic Adenocarcinoma. clinicaltrials.gov; 2026. Accessed March 19, 2026. https://clinicaltrials.gov/study/NCT03377491
  2. 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
  3. Siegel RL, Kratzer TB, Giaquinto AN, Sung H, Jemal A. Cancer statistics, 2025. CA Cancer J Clin. 2025;75(1):10-45. doi:10.3322/caac.21871
  4. Pancreatic cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. Annals of Oncology. 2023;34(11):987-1002. doi:10.1016/j.annonc.2023.08.009
  5. Cancer of the Pancreas – Cancer Stat Facts. SEER. Accessed March 19, 2026. https://seer.cancer.gov/statfacts/html/pancreas.html
  6. Pancreatic Cancer Treatment (PDQ®) – NCI. February 10, 2026. Accessed March 19, 2026. https://www.cancer.gov/types/pancreatic/hp/pancreatic-treatment-pdq
  7. Celgene. A Randomized Phase III Study of Weekly ABI-007 Plus Gemcitabine Versus Gemcitabine Alone in Patients With Metastatic Adenocarcinoma of the Pancreas. clinicaltrials.gov; 2019. Accessed April 2, 2026. https://clinicaltrials.gov/study/NCT00844649
  8. Disruption of Cancer Cell Replication by Alternating Electric Fields | Cancer Research | American Association for Cancer Research. Accessed March 19, 2026. https://aacrjournals.org/cancerres/article/64/9/3288/517864/Disruption-of-Cancer-Cell-Replication-by?guestAccessKey=
  9. Mumblat H, Martinez-Conde A, Braten O, et al. Tumor Treating Fields (TTFields) downregulate the Fanconi Anemia-BRCA pathway and increase the efficacy of chemotherapy in malignant pleural mesothelioma preclinical models. Lung Cancer. 2021;160:99-110. doi:10.1016/j.lungcan.2021.08.011
  10. Mumblat H, Martinez-Conde A, Braten O, et al. Tumor Treating Fields (TTFields) downregulate the Fanconi Anemia-BRCA pathway and increase the efficacy of chemotherapy in malignant pleural mesothelioma preclinical models. Lung Cancer. 2021;160:99-110. doi:10.1016/j.lungcan.2021.08.011
  11. Voloshin T, Kaynan N, Davidi S, et al. Tumor-treating fields (TTFields) induce immunogenic cell death resulting in enhanced antitumor efficacy when combined with anti-PD-1 therapy. Cancer Immunol Immunother. 2020;69(7):1191-1204. doi:10.1007/s00262-020-02534-7
  12. Chen D, Le SB, Hutchinson TE, et al. Tumor Treating Fields dually activate STING and AIM2 inflammasomes to induce adjuvant immunity in glioblastoma. J Clin Invest. 2022;132(8):e149258. doi:10.1172/JCI149258
  13. Kirson ED, Giladi M, Gurvich Z, et al. Alternating electric fields (TTFields) inhibit metastatic spread of solid tumors to the lungs. Clin Exp Metastasis. 2009;26(7):633-640. doi:10.1007/s10585-009-9262-y
  14. Giladi M, Schneiderman RS, Porat Y, et al. Mitotic disruption and reduced clonogenicity of pancreatic cancer cells in vitro and in vivo by tumor treating fields. Pancreatology. 2014;14(1):54-63. doi:10.1016/j.pan.2013.11.009
  15. Optune Gio® | FDA-approved glioblastoma (GBM) treatment. Optune Gio®. Accessed March 19, 2026. https://www.optunegio.com
  16. Premarket Approval (PMA). Accessed March 19, 2026. https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpma/pma.cfm?id=P230042
  17. Humanitarian Device Exemption (HDE). Accessed March 19, 2026. https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfhde/hde.cfm?id=H180002
  18. NovoCure Ltd. PANOVA-4: Pilot, Single Arm Study of Tumor Treating Fields (TTFields, 150kHz) Concomitant With Atezolizumab, Gemcitabine and Nab-Paclitaxel as First-Line Treatment for Metastatic Pancreatic Ductal Adenocarcinoma (mPDAC). clinicaltrials.gov; 2025. Accessed March 19, 2026. https://clinicaltrials.gov/study/NCT06390059
  19. Study Details | NCT06216301 | LUNAR-2: TTFields With Pembrolizumab + Platinum-based Chemotherapy for Metastatic NSCLC | ClinicalTrials.gov. Accessed March 19, 2026. https://clinicaltrials.gov/study/NCT06216301
  20. NovoCure GmbH. LUNAR-4: Pilot, Single Arm, Open-Label, Multinational Study of Tumor Treating Fields (TTFields, 150 kHz) Concomitant With Pembrolizumab for the Treatment of Metastatic Non-Small Cell Lung Cancer (NSCLC) Previously Treated With a PD-1/PD-L1 Inhibitor and Platinum-Based Chemotherapy. clinicaltrials.gov; 2025. Accessed March 19, 2026. https://clinicaltrials.gov/study/NCT06558799
  21. NovoCure GmbH. A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of Optune® (TTFields, 200 kHz) Concomitant With Maintenance Temozolomide and Pembrolizumab Versus Optune® Concomitant With Maintenance Temozolomide and Placebo for the Treatment of Newly Diagnosed Glioblastoma (EF-41/KEYNOTE D58). clinicaltrials.gov; 2026. Accessed March 19, 2026. https://clinicaltrials.gov/study/NCT06556563
  22. NovoCure Ltd. EF-32: Pivotal, Randomized, Open-Label Study of Optune® (Tumor Treating Fields, 200kHz) Concomitant With Radiation Therapy and Temozolomide for the Treatment of Newly Diagnosed Glioblastoma. clinicaltrials.gov; 2025. Accessed March 19, 2026. https://clinicaltrials.gov/study/NCT04471844
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