JCO at ASCO Annual Meeting: TTFields in Locally Advanced Pancreatic Adenocarcinoma

JCO Editorial Fellow Peter Li and JCO Associate Editor Eileen O'Reilly discuss the ASCO 25 Simultaneous Publication paper "Tumor-Treating Fields with Gemcitabine and Nab-Paclitaxel for Locally Advanced Pancreatic Adenocarcinoma: Randomized, Open-Label, Pivotal, Phase 3 PANOVA-3 Study."

Transcript

The guest on this podcast episode has no disclosures to declare.

Dr. Peter Li: Hello, and welcome to our 2025 ASCO Annual Meeting series, where we cover some of the top JCO papers published simultaneously with their abstract presentation at this year's meeting. I'm your host, Dr. Peter Li, and I'm joined by JCO Associate Editor Dr. Eileen O'Reilly to discuss the Journal of Clinical Oncology article and abstract presentation "Tumor Treating Fields with Gemcitabine and Nab-Paclitaxel for Locally Advanced Pancreatic Adenocarcinoma: Randomized, Open-Label, Pivotal, Phase 3 PANOVA-3 Study."

Now, let's start with the relevance of the article. Eileen, can you explain this study to our listeners?

Dr. Eileen O'Reilly: Thanks very much, Peter, for the invitation today to discuss this. Yes, so this is a positive phase 3 trial that was conducted in locally advanced, unresectable pancreas cancer. Patients were randomized to receive either gemcitabine and nab-paclitaxel, international standard, with or without tumor-treating fields. And this is a device like a battery pack that you would wear with a goal to wear that approximately 18 hours a day. And the primary endpoint of this study was overall survival, with key secondary endpoints of tumor response, progression-free survival, looking at pain-free survival, and distant progression-free survival.

So, the primary endpoint was met with a median overall survival of 16.2 months compared to 14.2 months on the intervention versus control arm, with a hazard ratio of 0.82. And so that met the pre-specified boundary. There was not an increase in progression-free survival, but there was an increase in control of pain on the tumor-treating fields study. So, it was a large, global study, community, academic sites, randomized 570 people, and it supports what I think we've seen in other difficult-to-treat malignancies using tumor-treating fields, that there's a signal of interest.

Dr. Peter Li: Can you speak to some of the strengths and weaknesses of this study?

Dr. Eileen O'Reilly: So, strengths: it was a large study. It included community sites, it included academic sites. It included ECOG performance status 0, 1, and some patients with 2. The intent was locally advanced. It probably is fair to say that there were some patients who had more advanced disease based on early progression, based on relatively high CA 19-9 for a percentage of people. But likely that was, with random assignment, that would have presumably fallen out between the arms. The inclusion of patients with a lower performance status is nice to see in large phase 3 studies in pancreas cancer. So, they would be some of the strengths.

So maybe some of the limitations are the fact that it's an open-label study - so, always some biases inherent in that. Acknowledging that the primary endpoint was overall survival, presumably that wouldn't be directly influenced by that. And there was an imbalance of women on the control arm, and women do fare a little better in this disease, so possibly kind of weighted one of the study arms a little bit. But nonetheless, I think it was a rigorously designed and rigorously conducted phase 3 trial.

It's always hard to fully interpret the signal in locally advanced disease because of the fact that some patients go on to surgery, some patients have a treatment switch of cytotoxic therapy, some patients will go on to radiation. And the endpoint here of overall survival, to a degree, eliminates some of that. So, the benchmark, I think, was generally high here.

Dr. Peter Li: Gotcha. And then with these findings and this positive study, how do you foresee this research being implemented and how it will impact clinical practice moving forward?

Dr. Eileen O'Reilly: I think there'll be an educational need to introduce this approach to the community and to the pancreas cancer world. Again, there's a precedent in glioblastoma and data from other diseases, so there's some familiarity with this. I think people always want to understand how it works and why it works, and that's something that we'll look forward to hearing more about mechanistically, and also seeing how it can be built upon. And there's some intriguing data with the combination of tumor-treating fields and immunotherapy that's being evaluated in the PANOVA-4 study. So, we'll stay tuned to hear how that reads out in due course. But I think overall, it'll be educational and learning, managing the cutaneous impacts or some skin irritation effects from this, and building on this signal in locally advanced disease.

Dr. Peter Li: Well, thank you so much, Eileen, for your time and for speaking about the JCO article, "Tumor Treating Fields with Gemcitabine and Nab-Paclitaxel for Locally Advanced Pancreatic Adenocarcinoma: Randomized, Open-Label, Pivotal, Phase 3 PANOVA-3 Study."

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