PANOVA-3 Post-Hoc Analyses Highlight Predictors of Benefit With TTFields Therapy in Pancreatic Adenocarcinoma
Key Clinical Takeaways
- Design/Population: In exploratory post-hoc analyses of the phase 3 PANOVA-3 trial 266 patients with unresectable locally advanced pancreatic adenocarcinoma received gemcitabine plus nab-paclitaxel with or without TTFields, a wearable device delivering low-intensity electric fields to disrupt tumor cell division.
- Key Outcomes: TTFields plus gemcitabine and nab-paclitaxe improved median OS vs gemcitabine and nab-paclitaxel alone (17.1 vs 14.2 mo; HR 0.71; P = .003). Patients with ≥50% TTFields adherence or >50% CA 19-9 decline by week 8 had superior OS (18.6 vs 14.7 mo; HR 0.74; P = .028). Benefit was most pronounced in those with elevated baseline CA 19-9 (>500–1000 U/mL).
- Clinical Relevance: Higher TTFields adherence and early CA 19-9 reductions correlated with improved survival, suggesting these may serve as early predictive markers to guide therapy optimization in locally advanced pancreatic cancer.
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 tumor treating fields (TTFields) plus gemcitabine and nab-paclitaxel (GnP), according to exploratory post-hoc analyses from the phase 3 PANOVA-3 trial.
These findings, presented by Hani Babiker, MD, Mayo Clinic, Jacksonville, Florida, at the 2025 ESMO Congress, build upon previously reported overall survival (OS) benefits for TTFields plus GnP vs GnP alone in the primary analysis of PANOVA-3 (median OS 16.2 vs 14.2 months; hazard ratio [HR], 0.82; P = .039).
TTFields are low-intensity alternating electric fields delivered noninvasively via a wearable device, designed to disrupt mitotic spindle formation and inhibit tumor cell division. In PANOVA-3, patients with previously untreated, unresectable locally advanced pancreatic adenocarcinoma were randomized 1:1 to receive GnP with or without TTFields. Target device adherence was ≥75% of daily usage, with real-time data captured over the first 3 months of treatment.
In this post-hoc analysis, device usage ≥50% during the first 3 months was strongly associated with superior survival outcomes. Among patients in the TTFields plus GnP arm (n = 166), median OS reached 17.1 months compared with 14.2 months for GnP alone (HR, 0.71; P = .003). In contrast, patients with TTFields usage <50% had a median OS of 13.8 months, underscoring the importance of treatment adherence for clinical benefit.
Serum CA 19-9 dynamics also emerged as a predictive biomarker of response. Patients receiving TTFields plus GnP who achieved a >50% decline in CA 19-9 by week 8 (n = 137) experienced longer median OS compared with those receiving GnP alone (18.6 vs 14.7 months, respectively; HR, 0.74; P = .028). Additionally, greater relative benefit from TTFields was observed among patients with elevated baseline CA 19-9 levels, particularly those with CA 19-9 >500 U/mL (15.4 vs 12.1 months, respectively) or >1000 U/mL (14.3 vs 11.5 months, respectively).
According to Dr Babiker and coauthors, these findings suggest that both TTFields adherence and CA 19-9 response may serve as early, clinically relevant markers of TTFields efficacy, enabling clinicians to identify patients most likely to benefit from this novel modality.
Ongoing exploratory analyses aim to further validate these relationships and refine treatment optimization strategies in locally advanced pancreatic adenocarcinoma.
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
