Hani Babiker, MD, Mayo Clinic, Jacksonville, Florida, discusses findings from exploratory post-hoc analyses of overall survival from the PANOVA-3 trial based on tumor treating fields (TTFields) device usage and CA 19-9 levels. 

The analyses showed that higher device adherence and reductions in CA 19-9 levels may serve as early indicators of improved survival in patients with unresectable locally advanced pancreatic adenocarcinoma treated with TTFields plus gemcitabine and nab-paclitaxel.

These findings were presented at the 2025 European Society of Clinical Oncology (ESMO) Congress. 

Transcript: 

My name is Hani Babiker, I'm a GI oncologist and a drug developer, physician-scientist at the Mayo Clinic in Florida. At the ESMO Congress 2025 in Berlin, we introduced a biomarker study that is a follow-up to our study that was presented at ASCO this year, with simultaneous publication in Journal of Clinical Oncology, the PANOVA-3 trial. We did present at ASCO this year, in Chicago, a randomized phase 3 trial investigating the role of gemcitabine plus abraxane versus Tumor Treating Fields (TTFields) with gemcitabine plus nab-paclitaxel or abraxane in patients with locally advanced unresectable [pancreatic] cancer. 

Just to give you a little bit of background about pancreatic cancer, unfortunately pancreatic cancer is a lethal disease. The 5-year survival is 13% for the Surveillance, Epidemiology, and End Results and most importantly, for metastatic pancreatic cancer, the 5-year survival is 3.1% so, there’s an absolute unmet need to develop novel therapeutics in pancreatic cancer to help patients and improve survival. Most importantly, many of the drugs we administer do have some side effects for patients such as cytopenias, nausea and vomiting, and other symptoms hence, identifying a therapeutic modality that not only is effective but tolerable is quintessential. In pancreatic cancer it is even more important since the incidence of pancreatic cancer is increasing and we're seeing it in younger patients. Pancreatic cancer is predicted to become the second leading cause of cancer death in a few years to come. In clinic, we are seeing younger patients present with this disease. It's also important to note that 80% to 85% of patients with pancreatic cancer present with metastatic disease so, many of the patients that we do see in clinic, due to multiple reasons, present with really advanced disease, again highlighting the importance of developing novel therapeutics in this disease—most importantly in locally advanced and unresectable disease—because there are not a lot of trials that really focus on locally advanced and unresectable disease. We do know that from ASCO GI this year, the LAPIS trial, that unfortunately we were very excited about, did not yield a survival benefit. It shows that this is a disease we really need to focus on and try to fight. 

The PANOVA-3 trial was a randomized, international trial that was studied based on a positive phase 2 trial and based on preclinical data showing efficacy for adding TTFields to chemo[therapy]. Now, TTFields are intermediate-frequency, low-intensity, electrical fields that inhibit cancer cells from proliferation. This was studied previously scientifically, and we do know that it affects cell division and cell proliferation through multiple mechanisms. In the initial studies, preclinical studies show that it inhibits tubulin polymerization and inhibits proliferation of cancer and affects the cell cycle. Multiple other scientific studies show that it affects permeability of cancer cells and it affects autophagy and, most importantly, affects other pathways that lead to cancer growth. A phase 2 trial showed a benefit to the addition of TTFields to gemcitabine alone and gemcitabine plus nab-paclitaxel [and] that led to this international phase 3 trial that randomized patients to chemotherapy alone, which is gemcitabine plus nab-paclitaxel, versus TTFields plus gemcitabine or with gemcitabine plus nab-paclitaxel. This was a 1:1 randomization, the primary end point was overall survival. Secondary end points included local PFS (progression-free survival), PFS, overall response rate, pain-free survival, and we also looked at quality of life. 

As presented at ASCO and published in Journal of Clinical Oncology the trial did meet its primary end point of overall survival, showing a benefit for patients with locally advanced and unresectable disease to receive TTFields with chemotherapy—gemcitabine plus nab-paclitaxel. We were very excited about that data, given that it could help many patients with this lethal disease. As I previously mentioned, the trial showed there was a trend toward improvement in local PFS and PFS, although it was statistically not significant but the 12-month PFS rate was significant, showing there is a cohort of patients that derive not only an overall survival benefit but a PFS benefit. The trial also showed that there was improvement in pain-free survival for patients who were randomized to the investigational arm and also improvement in quality of life. This was later presented at ESMO GI, showing that the addition of TTFields to chemotherapy improves patients’ quality of life, survival, and pain-free survival. Most importantly, as we know, patients with pancreatic cancer present with pancreatic exocrine insufficiency and do have symptoms of digestive issues such as loose stools and diarrhea. There was an improvement in these digestive symptoms in the investigational arm hence, we were very excited about the data showing that there is a benefit for this cohort of patients, which is really an unmet need—not only effectiveness but also treating symptoms because of the cancer itself, such as pain, which is the most common presenting symptom for our patients with pancreatic cancer, and it’s a symptom that affects both receiving and continuing treatment.

At the ESMO Congress 2025 here in Berlin, we presented biomarkers to try to identify who are really those people that derive those survival benefits. Could we have a specific biomarker? So, we looked at usage and compliance with the device. What we found was we divided patients into less than 50% usage per day or more than 50% usage per day of TTFields. And we did find that the patients who were more compliant—more than 50%—derived a survival benefit, showing that at least having a 50% compliance and above did lead to a survival benefit as opposed to patients who did not. In addition, we also looked at CA 19-9. We know that CA 19-9 is a big biomarker in pancreatic cancer, and there is a point of a decrease of more than 50% of CA 19-9 at 8 weeks per previous published data that did show that patients that achieved this mark can have a survival benefit. So, that’s a marker we looked at, and we indeed found patients that had a decrease in CA 19-9 by more than 50% at eight weeks had a survival benefit to the investigational arm. Again, this is a big trial with 571 patients, so it’s a high-powered trial. We also divided the CA 19-9 based on different levels of less than 37, 38 to 500, and 500 to 1000, and we did find with any CA 19-9 level above 37 units, there was a survival benefit for patients and a trend at the level of 500 to 1000. But again, to allude back to the decrease in CA 19-9 by more than 50% at 8 weeks, there was an improvement in survival for the patients who were randomized to the investigational arm. So, this is really exciting that finally we’re seeing progress in the road for fighting pancreatic cancer. 

Again, these are noninvasive arrays that are placed on the skin aimed at where the cancer is and inhibit cancer proliferation. It’s been studied scientifically, identifying different mechanisms, so it’s really noninvasive. The only side effect that most patients had was 8% or less that had grade 3 rash because of the arrays and the electrical fields, but it was very well treatable and tolerable so, we’re very excited for that. We are very hopeful in the future we’re going to see more avenues for not only devices but for drugs to fight pancreatic cancer. But we’re excited right now—there’s potential for a device plus drugs or other drugs to push effective treatment to fight pancreatic cancer.

Source:

Babiker H, Mercade TM, Dragovich T, et al. Phase III study of TTFields in locally advanced pancreatic adenocarcinoma (PANOVA-3): Post-hoc subgroup analyses based on device usage and CA 19-9. Presented at the 2025 ESMO Congress; October 17-21, 2025. Berlin, Germany. 2235P