Tumor treating fields (150 kHz) with standard chemotherapy in advanced pancreatic adenocarcinoma – the PANOVA studies

Background

Tumor Treating Fields (TTFields) are a non-invasive, regional antimitotic treatment modality approved for the treatment of glioblastoma. TTFields disrupt the formation of the mitotic spindle during metaphase. TTFields were effective in multiple preclinical models of pancreatic cancer. We present the results of the Phase 2 PANOVA-2 trial [NCT01971281] that tested TTFields plus either gemcitabine or gemcitabine/nab-paclitaxel in pancreatic cancer patients.

Methods

Chemotherapy-naïve patients (n=20/arm) with histologically-confirmed, unresectable pancreatic adenocarcinoma received continuous TTFields (150 kHz for >18 hours/day) plus gemcitabine (1000 mg/m²/weekly) or TTFields/gemcitabine/nab-paclitaxel (125 mg/m²). The primary endpoint was safety (severity and frequency of adverse events [AEs]). Secondary endpoints included progression-free survival (PFS) and overall survival (OS).

Results: In the TTFields + gemcitabine arm, 17 patients (85%) reported Grade 3-4 adverse events during the study period. The majority of systemic adverse events seen in the trial were related to the underlying malignancy or systemic therapies. The only TTFields-related toxicity seen was Grades 1–2 dermatitis beneath the transducer arrays reported in 8 (40%) patients. Dermatitis of Grade 3 severity occurred in only 2 (10%) patients but resolved after a short break in treatment. TTFields in combination with gemcitabine showed a median progression-free survival (PFS) of 8.3 months and an overall survival (OS) of 14.9 months. TTFields in combination with nab-paclitaxel and gemcitabine showed a median PFS of 12.7 months (95% confidence interval [CI] 5.4, NA). The median OS was not reached, and the 1-year survival rate was 72%.

Conclusions

TTFields concomitant to gemcitabine and nab-paclitaxel are safe for advanced pancreatic cancer patients with encouraging survival outcomes. Based on these results, a phase III trial PANOVA-3 [NCT0337749] is underway to test the efficacy of TTFields combined with gemcitabine and nab-paclitaxel in 556 locally-advanced pancreatic cancer patients.