TTFields/Chemotherapy Improves Survival in Advanced Pancreatic Cancer

Tumor treating fields with chemotherapy improved overall survival for patients with unresectable, locally advanced pancreatic adenocarcinoma.

The prospective, randomized, open-label, controlled phase 3 PANOVA-3 trial (NCT03377491) treating patients with unresectable, locally advanced pancreatic adenocarcinoma in the first-line setting with tumor treating fields (TTFields) concomitantly with gemcitabine (Gemzar) and nab-paclitaxel (Abraxane) has met its primary end point of overall survival (OS), according to a press release from the developer, Novocure.¹

As a next step, the developer looks to file for regulatory approval of TTFields for this population in the US, EU, Japan, and other key markets, and to submit the trial results for presentation at an upcoming medical conference.

In the trial, median OS for patients treated with TTFields therapy concomitant with gemcitabine and nab-paclitaxel was 16.20 months vs 14.16 months in patients treated only with gemcitabine and nab-paclitaxel (HR, 0.819; P = .039). Patients treated with TTFields had a 13% improvement in the OS rate at 12 months and a 33% improvement at 24 months.

Safety was consistent with other clinical studies, and TTFields therapy was well-tolerated.

The primary trial end point was OS at a time frame of 4 years.² Key secondary end points were progression-free survival, objective response rate, quality of life, pain-free survival, puncture-free survival, resectability rate, and toxicity profile.

Vincent Picozzi, MD, a medical oncologist from Virginia Mason Franciscan Health and investigator in the PANOVA-3 trial, said in a press release, “As a researcher and clinician, I have experienced the challenges of developing treatments in pancreatic cancer. It is exciting to see the PANOVA-3 trial achieve the positive primary end point of [OS], a landmark outcome for this field. These data for tumor treating fields are very promising, especially in this difficult-to-treat patient population.”¹

The PANOVA-3 trial enrolled 571 patients who were randomly assigned, in a 1:1 ratio, to 1 of 2 trial arms. In the experimental arm, patients received continuous TTFields treatment through the NovoTTF-200T device with 125 mg/m² of nab-paclitaxel administered as an intravenous infusion over 30 to 40 minutes on days 1, 8, and 15 of each 28 day cycle and a 1000 mg/m² infusion of gemcitabine over 30 minutes immediately following the nab-paclitaxel on days 1, 8, and 15 of each 28 day cycle. In the control arm, investigators used the best standard-of-care treatment with nab-paclitaxel and gemcitabine at the same dosage.

The TTField therapy consisted of 4 electrically insulated electrode arrays being worn on the torso, and treatment with the NovoTTF-200T device was administered continuously until patients experienced progression in the abdomen.

NovoTTF-200T previously received breakthrough device designation from the FDA in September 2021 for advanced liver cancer.³

Patient eligibility criteria included: being 18 years of age or older; a life expectancy of 3 months or more; histological or cytological diagnosis of de novo pancreatic adenocarcinoma; unresectable, locally advanced stage disease; and an ECOG performance score from 0 to 2.

Patients were ineligible if they had any of the following: prior palliative treatment to the tumor, cancer requiring anti-tumor treatment within 5 years before inclusion, concurrent anti-tumor therapy beyond gemcitabine and nab-paclitaxel, implantable electronic medical devices in the torso (ie. pacemaker), or one of several co-morbidities like history of cardiovascular disease or arrhythmia that is symptomatic or requires treatment, among other exclusion criteria.

“PANOVA-3 is the first and only phase 3 trial to demonstrate a statistically significant benefit in [OS], specifically in unresectable, locally advanced pancreatic cancer, and is Novocure’s third positive phase 3 clinical trial in the last 2 years. We are grateful to the patients and investigators for their participation in the trial, and we look forward to sharing the full data at an upcoming medical conference,” Nicolas Leupin, MD, PhD, chief medical officer at Novocure, said in a press release.¹

In addition to PANOVA-3, Novacure is also exploring the treatment of patients with metastatic pancreatic cancer in the phase 2 PANOVA-4 trial (NCT06390059), which will analyze the use of TTFields with atezolizumab (Tecentriq), gemcitabine, and nab-paclitaxel. Data are expected in 2026.

References

1. Novocure announces positive topline results from phase 3 PANOVA-3 clinical trial of tumor treating fields (TTFields) therapy for pancreatic cancer. News release. Novocure. December 2, 2024. Accessed December 3, 2024. https://tinyurl.com/4ewpbcaf
2. Effect of tumor treating fields (TTFields, 150 kHz) as front-line treatment of locally-advanced pancreatic adenocarcinoma concomitant with gemcitabine and nab-paclitaxel (PANOVA-3). ClinicalTrials.gov. Updated October 31, 2024. Accessed December 3, 2024. https://tinyurl.com/mwp9c553
3. FDA grants breakthrough device designation to the NovoTTF-200T™ System for advanced liver cancer. News release. Novocure. September 10, 2021. Accessed December 3, 2024. https://bwnews.pr/2YKk6q9