Abstract CT130: PANOVA: A phase II study of TTFields (150kHz) concomitant with standard chemotherapy for front line therapy of advanced pancreatic adenocarcinoma

Abstract

Abstract Background Ductal adenocarcinoma of the pancreas is the fourth leading cause of cancer mortality in the US. The disease is mostly unresectable at the time of diagnosis, making chemotherapy the backbone of therapy. TTFields are a non-invasive, regional antimitotic treatment modality, which has been approved for the treatment of recurrent and newly diagnosed glioblastoma by the FDA. TTFields act by delivering intermediate frequency alternating electric fields to the tumor, and act predominantly by disrupting the formation of the mitotic spindle during metaphase and by dielectrophoretic dislocation of intracellular constituents during cytokinesis. In vitro, TTFields led to reduction in the proliferative potential of pancreatic cancer cell lines with or without chemotherapies, and to a subsequent reduction in their clonogenic potential. In vivo, TTFields led to a significant reduction in tumor volumes. PANOVA was the first trial testing TTFields (150kHz) in pancreatic cancer patients. Results from the first arm of the study, testing TTFields in combination with gemcitabine, have demonstrated superiority in efficacy compared to historical controls, with median PFS of 8.3 months and median OS of 14.9 months (Rivera F. et al, J Clin Oncol 34, 2016 (suppl 4S; abstr 269)). Methods Twenty advanced pancreatic cancer patients were enrolled in the second arm of PANOVA and treated with TTFields in combination with gemcitabine concomitant to nab-paclitaxel. 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 68.2 (range – 58-81) and most patients (65%) had an ECOG score of 1. Twelve patients (60%) had distant metastases. The Median number of gem/nab-paclitaxel cycles was 5.0, and median number of TTFields cycles was 7.5. Ten patients (50%) had serious AEs during the study period. Eleven patients (55%) had treatment-related skin toxicity, of which 5 had grade 3 toxicity. No TTFields-related serious AEs were reported. The median PFS was 12.7 months (95% CI 5.4, NA). PFS rate at 6 months was 65%. Of the evaluable tumors, 40% had partial response and another 47% stable disease. The median OS was not reached, and the 1-year survival rate was 72%. Conclusions TTFields concomitant to gemcitabine and nab-paclitaxel are tolerable and safe for advanced pancreatic cancer patients, with promising clinical outcome which doubled published historical data. A phase III trial is planned, testing the efficacy of TTFields combined with gemcitabine and nab-paclitaxel in locally-advanced pancreatic cancer patients. Citation Format: Manuel Benavides, Carmen Guillen, Fernando Rivera, Javier Gallego, Jose Lopez-Martin, Marc Küng. PANOVA: A phase II study of TTFields (150kHz) concomitant with standard chemotherapy for front line therapy of advanced pancreatic adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr CT130. doi:10.1158/1538-7445.AM2017-CT130