PANOVA: A pilot study of TTFields concomitant with gemcitabine for front-line therapy of advanced pancreatic adenocarcinoma.

Abstract

4125 Background: TTFields are alternating electric fields delivered to the region of the tumor by means of non-invasive transducer arrays surrounding the abdominal region. TTFields have an anti-mitotic effect by interfering with mitotic spindle formation, leading to apoptosis. In pancreatic cancer, TTFields decreased proliferation and clonogenic potential in vitro, and reduced tumor volume in vivo. The PANOVA trial is the first study testing TTFields in pancreatic cancer patients. Methods: Twenty advanced pancreatic cancer patients were enrolled in a prospective study of TTFields concomitant with weekly gemcitabine. All patients had unresectable tumors, an ECOG performance score of 0-1 and no prior therapy. The primary endpoint was the incidence and severity of treatment emergent adverse events. Results: The median age was 73 (range – 49-81) and most patients (80%) had an ECOG score of 1. Thirteen patients (65%) had distant metastases. Median compliance with TTFields was 78% (14 hours/day), with median duration of 5 months. Fourteen patients (70%) had serious AEs during the study period. Ten patients (50%) had treatment-related skin toxicity, of which only 2 were grade 3, both resolved with appropriate treatment. No TTFields-related serious AEs were reported. The median PFS was 8.3 months (95% CI 4.3, 10.3): 10.3 months (95% CI 2.8, NA) in locally advanced patients and 5.7 months (95% CI 3.8 - 10.3) in patients with metastatic disease. PFS rate at 6 months was 56%. Of the evaluable tumors, 30% had partial response and another 30% stable disease. The median OS for all patients was 14.9 months: It was not reached after 15 months in locally advanced patients, and was 8.3 months (95% CI 4.3-14.9) in patients with metastatic disease. The 1-year survival rate was 55% (86% in locally advanced and 40% in metastatic disease). Conclusions: TTFields concomitant to gemcitabine are tolerable and safe for advanced pancreatic cancer patients, with promising clinical outcome compared to published data for gemcitabine alone. An extension of the current protocol is testing patients treated with gemcitabine, nab-paclitaxel and TTFields. Clinical trial information: NCT01971281.