TTFields Plus Chemo Shows Benefit in Pancreatic Cancer

Roxanne Nelson

January 26, 2016

SAN FRANCISCO — Tumor-treating fields (TTFields, Novocure) therapy, already approved for use in glioblastoma, has now shown benefit in patients with advanced pancreatic cancer.

TTFields combined with gemcitabine (Gemzar, Lilly) is tolerable and safe in patients with advanced pancreatic cancer, according to findings from a small pilot study presented here at the Gastrointestinal Cancers Symposium 2016.

The data also indicate that survival and response rates are better with the combination than with gemcitabine alone.

"These are very early data in pancreatic cancer. They are very encouraging, with a lot of promise," said study investigator Uri Weinberg, MD, PhD, vice president of research and development at Novocure.

TTFields are a novel, experimental treatment for pancreatic cancer, said Smitha S. Krishnamurthi, MD, from the division of hematology and oncology at University Hospitals Case Medical Center and Case Western Reserve University in Cleveland, and an American Society of Clinical Oncology expert.

"TTFields are of interest, given the activity demonstrated in glioblastoma multiforme, the toxicity profile, and the preliminary results observed with TTFields in combination with gemcitabine in patients with metastatic pancreatic cancer," Dr Krishnamurthi told Medscape Medical News. "Ultimately, a randomized controlled trial will be necessary to determine if TTFields will be effective against pancreatic cancer."

Noninvasive Treatment

TTFields are a noninvasive, regional antimitotic treatment. They work by delivering low-intensity intermediate frequency, and alternate electric fields to the tumor using transducer arrays that are placed on the skin around the region of the body containing the tumor, according to the manufacturer. The therapy disrupts cell division by physically interacting with key molecules during mitosis. Dr Weinberg noted that the preclinical data "show that by adjusting the electrical properties of the technology, TTFields could be used to target multiple cancer types."

"Our clinical experience has been primarily with glioblastoma," Dr Weinberg told Medscape Medical News. "We had two phase 3 pivotal trials in recurrent and newly diagnosed glioblastoma, and TTFields demonstrated efficacy and improved overall survival."

The device was approved by the US Food and Drug Administration in 2011 for the treatment of adults with glioblastoma multiforme who experience tumor recurrence after chemotherapy.

In a recent study, the addition of TTFields to temozolomide (Temodar, Merck Sharp & Dohme Corp.) in patients with newly diagnosed glioblastoma led to a survival benefit, compared with temozolomide alone.

"Based on those results and preclinical data, we are currently investigating its use in a number of other cancers, including pancreatic cancer, ovarian cancer, brain metastasis from non-small-cell lung cancer, and mesothelioma," Dr Weinberg reported. "All of these are currently ongoing in clinical trials, and this is the first time we are presenting data in pancreatic cancer."

Better Survival Than Seen Historically

The data on pancreatic cancer come from the PANOVA trial, which involved 20 patients treated with TTFields 150 kHz for at least 18 hours a day, concomitant with standard weekly gemcitabine (1000 mg/m² once weekly for up to 7 weeks, with subsequent weekly infusions on days 1, 8, and 15 every 28 days).

All patients had histologically confirmed unresectable tumors and an ECOG performance score of 0 or 1, were treatment-naïve, and had received no previous chemotherapy or radiation therapy.

Median age in the study cohort was 73 years (range, 49 - 81), and 60% of the patients were women. Most patients (80%) had an ECOG score of 1, and 12 (60%) had distant metastases; the remaining patients had locally advanced disease.

The median compliance with TTFields was 78% (14 hours/day), with a median duration of 5 months.

For patients who received TTFields therapy plus first-line gemcitabine, median progression-free survival was 8.3 months, median overall survival was 14.9 months, and median 1-year survival was 55%.

All of these results are better than what has been seen historically in patients with advanced pancreatic cancer, Dr Weinberg and his colleagues note. As a reference, they cite data from a study in which median progression-free survival was 3.7 months in the control group receiving gemcitabine alone, median overall survival was 6.7 months, and median 1-year survival of 22% (N Engl J Med. 2013;369:1691-1703).

Of patients with evaluable tumors, 30% achieved a partial response and 30% achieved stable disease.

During the study period, 14 patients (70%) experienced serious (grade 3 to 5) adverse events — 30% of which were hematologic, 45% of which were gastrointestinal, and 15% of which were pulmonary. There were no serious events related to TTFields, Dr Weinberg reported.

"The main problem was dermatitis," he said. "That was experienced by about half of the patients, and was easily managed with topical treatments."

The investigators are now in the process of enrolling 20 more patients. "These patients will be receiving gemcitabine, nab-paclitaxel, and TTFields," Dr Weinberg explained. The next step "will be to open a phase 3 trial with patients who have brain metastasis from non-small-cell lung cancer."

The study was funded by Novocure. Dr Krishnamurthi has disclosed no relevant financial relationships. Coauthor Fernando Rivera, MD, from Hospital Universitario Marqués de Valdecilla in Santander, Spain, reports receiving research funding from Novocure. Coauthor Jose Lopez-Martin, MD, from Hospital 12 de Octubre in Madrid, Spain, reports serving in a consulting or advisory role for Bristol-Myers Squibb, Caris MPI, GlaxoSmithKline, Lilly, MSD, and Roche/Genentech; and receiving research funding from Bristol-Myers Squibb, GlaxoSmithKline, MSD, Novartis, and Roche.

Gastrointestinal Cancers Symposium (GICS) 2016: Abstract 269. Presented January 22, 2016.

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