Vincent J. Picozzi Jr, MD, Hematologist/Oncologist from Virginia Mason Medical Center. In this interview, he speaks about the ASCO GI 2022 Abstract – PANOVA-3: A phase 3 study of tumor treating fields (TTFields) with gemcitabine and nab-paclitaxel (GnP) for front-line treatment of locally advanced pancreatic adenocarcinoma.
Origins:
Tumor Treating Fields (TTFields) is a non-invasive, loco-regional antimitotic therapy for glioblastoma and malignant pleural mesothelioma. TTFields (150"“200 kHz) are given to the tumor site via arrays implanted on the skin. TTFields (150 kHz) demonstrated antiproliferative and anticlonogenic effects on pancreatic cancer cells in vitro, with or without treatment. In both metastatic and locally advanced pancreatic cancer, the Phase 2 PANOVA study (NCT01971281) revealed the safety and preliminary efficacy of TTFields coupled with nab-paclitaxel and gemcitabine (GnP) (LAPC).
Methodologies:
The Phase 3 PANOVA-3 trial (NCT03377491) will assess the efficacy and safety of combining TTFields with GnP in a broader cohort of LAPC patients. This randomized trial is presently enrolling 556 individuals who have unresectable LAPC (as defined by the National Comprehensive Cancer Network), an Eastern Cooperative Oncology Group performance level of 0-2, and no prior progression or therapy. Patients will be randomly assigned to receive either TTFields with GnP or GnP alone, based on their performance status and geographic location. The use of a smaller, lighter-weight (from 6 to 2.7 lbs.) TTFields device was recently added to the protocol. On days 1, 8, and 15 of a 28-day cycle, standard dosages of nab-paclitaxel (125 mg/m2) and gemcitabine (1000 mg/m2) will be given. According to the Response Evaluation Criteria In Solid Tumors Criteria V1.1, TTFields (150 kHz) will be given for 18 hours each day until local disease progression. Every four weeks, a computed tomography scan of the chest and abdomen will be performed; every eight weeks, a computed tomography scan of the chest and abdomen will be performed. Patients will be tracked for survival on a monthly basis after local disease development. Overall survival is the key outcome (OS). PFS, local PFS, objective response rate, 1-year survival rate, pain- and puncture-free survival rate, rate of resectability, quality of life, and toxicity are all secondary objectives. A log-rank test was utilized to determine the sample size by comparing time to event in patients treated with TTFields + GnP versus patients treated with gemcitabine alone. PANOVA-3 is a statistical test that looks for a hazard ratio of 0.75 in OS. The power is set to 80% and the type I error is set to 0.05 (2-sided). Study locations are now recruiting in Austria, Belgium, Canada, Croatia, the Czech Republic, France, Germany, Hong Kong, Hungary, Israel, Italy, Poland, Spain, Switzerland, and the United States. NCT03377491 is the number for the clinical trial.