Dr O’Reilly on the Potential of TTFields in Unresectable, Locally Advanced Pancreatic Cancer

“[PANOVA-3] is an interesting and positive study looking at the addition of tumor treating fields to gemcitabine/nab-paclitaxel in locally advanced, unresectable pancreatic cancer. This trial met its primary end point of overall survival.”

Eileen M. O’Reilly, MD, the Winthrop Rockefeller Endowed Chair of Medical Oncology and section head of hepatopancreaticobi at Memorial Sloan Kettering Cancer Center, as well as codirector of medical initiatives at the David M. Rubenstein Center for Pancreatic Cancer Research, discussed the potential of tumor treating fields (TTFields) in patients with unresectable, locally advanced pancreatic adenocarcinoma.

The randomized, open-label, global, multicenter phase 3 PANOVA-3 trial (NCT03377491) evaluated gemcitabine plus nab-paclitaxel (Abraxane) with or without TTFields for the treatment of patients with newly diagnosed unresectable, locally advanced pancreatic adenocarcinoma. Of note, the primary end point was overall survival (OS), with secondary end points including progression-free survival (PFS), local PFS, pain-free survival, and overall response rate (ORR).

Findings from PANOVA-3 trial showed that the study met its primary end point, O’Reilly began. Notably, the median OS was 16.2 months (95% CI, 15.0-18.0) and 14.2 months (95% CI, 12.8-15.4) in the gemcitabine/nab-paclitaxel plus TTFields (n = 285) vs the gemcitabine/nab-paclitaxel (n = 286) arms, respectively (HR, 0.82; 95% CI, 0.68-0.99; log-rank P = .039). Furthermore, the 1-year OS rate was significantly improved with concomitant TTFields compared with gemcitabine/nab-paclitaxel, specifically at 68.1% (95% CI, 62.0%-73.5%) vs 60.2% (95% CI, 54.2%-65.7%) in the respective arms (P = .029).

The data also demonstrated a reduction in pain for patients who were treated with TTFields, of which pain is a significant aspect of locally advanced pancreatic cancer, O’Reilly noted. The results revealed that pain-free survival was significantly prolonged with TTFields with gemcitabine/nab-paclitaxel compared with the chemotherapy regimen alone. In particular, the median pain-free survival was 15.2 months (95% CI, 10.3-22.8) and 9.1 months (95% CI, 7.4-12.7) in the TTFields plus gemcitabine/nab-paclitaxel compared with gemcitabine/nab-paclitaxel alone, respectively (HR, 0.74; 95% CI, 0.56-0.97; log-rank P = .027).

Looking ahead, identifying whether TTFields can be combined with local therapies and immunotherapy could be a potential next step, O’Reilly said. Currently, there are a handful of positive pancreatic cancer trials, with PANOVA-3 as a first in the local advanced setting, she concluded.