TTFields are a non-invasive, regional antimitotic treatment modality approved for the treatment of glioblastoma. TTFields act by disrupting mitotic spindle formation during metaphase. TTFields were effective in preclinical models of pancreatic cancer. PANOVA was the first trial testing TTFields in pancreatic cancer. Results from the first arm of the study, testing TTFields in combination with gemcitabine, have demonstrated superiority in efficacy versus historical controls (J Clin Oncol 34, 2016 (suppl 4S; abstr 269).
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, ECOG score of 0-1 and no prior therapy. The primary endpoint was the incidence and severity of adverse events.
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. 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): 9.3 months in patients with metastatic disease, and not reached in locally-advanced patients. PFS rate at 6 months was 65%: 50% in metastatic disease and 87.5% in locally advanced patients. 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% (62.5% in metastatic disease and 87.5% in locally advanced disease). None of the patients who had a minimal average compliance of 75% died during the follow up period. 87% of the evaluable patients (including all metastatic patients) had a decrease in CA-19-9 levels.
TTFields concomitant to gemcitabine and nab-paclitaxel are safe for advanced pancreatic cancer patients, with promising clinical outcome which doubled 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.
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C. Guillen-Ponce: Advisor/board member: Merck Serono, Roche Pharma, Bayer, Sanofi Aventis, Celgene, Novocure. - Speaker’s bureau: Celgene, Merck Serono, Roche Pharma. - Travel and accommodation: Celgene, Roche Pharma, Sanofi Aventis, Merck Serono. F. Rivera Herrero: Grants/research: Celgene, Amgen. Merck-Serono, MSD, Lilly, Roche, Sanofi, Bayer, Advisor/board member: Celgene, Amgen. Merck-Serono, Lilly, Roche, Sanofi, Bayer, Servier, Baxalta Consultant/independent contractor: Celgene, Amgen. J. Gallego Plazas: Advisor/board member: Amgen, Lilly, Roche, Merck. Honorarium: Amgen, Lilly, Roche, Merck. All other authors have declared no conflicts of interest.