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    CPMC’s pancreatic cancer research highlighted at the ASCO Gastrointestinal Cancers annual international congress

    January 18, 2016

    Combining chemotherapy with an investigational enzyme that lowers pressure within tumors may double the amount of time some patients with metastatic pancreatic cancer have before their disease progresses, according to an interim analysis of data from an ongoing phase II trial. The study was co-authored by CPMCs’ Ari Baron, MD, Medical Director of the Clinical Oncology Research Program.

    Results will be presented this week in San Francisco at the American Society of Clinical Oncology’s annual gastrointestinal (GI) cancers meeting—one of the largest conferences worldwide devoted to GI cancer research.

    The study – led by investigators at the Fred Hutchinson Cancer Research Center – combines standard-of-care combination chemotherapy for advanced pancreatic cancer with the enzyme PEGPH20 (PEGylated recombinant human hyaluronidase). Hyaluronic acid (HA) is produced excessively in some tumors and has been linked to poor prognosis.

    In tumors with high amounts of HA, water-absorbing HA draws moisture from surrounding tissues into the tumor, increasing pressure and preventing drugs travelling through the bloodstream from effectively attacking cancer cells.
    “Biomarker-driven therapies such as the one explored in our study offer the potential for personalized cancer treatment,” said Dr. Baron. “We saw dramatic improvements in progression-free survival in patients whose tumors had the target for enzymatic therapy.”

    In the randomized, open-label study, 135 previously untreated patients received PEGPH20 plus the chemotherapies nab-pacliltaxel and gemcitabine or these chemotherapies alone.

    The primary endpoint of the study was progression-free survival (PFS).

    After a median follow-up of seven months, results showed that high-HA patients treated with PEGylated therapy plus chemotherapy achieved a PFS of 9.2 months, versus 4.3 months in those treated with chemotherapy alone (p=0.05); in contrast, low-HA patients showed no PFS improvements when treated with the enzyme-chemotherapy combination (5.3 months, versus 5.6 months in patients treated with chemotherapy alone, p=0.74).

    In March 2016, Dr. Baron and colleagues will begin a larger phase III trial assessing the impact of PEGylated therapy plus chemotherapy on survival in high-HA patients, to confirm preliminary results seen in the present study.

    “The presence of hyaluronic acid in tumors predicted response and thus underscores the potential for cancer therapies matched to biomarkers,” said Dr. Baron. “We are eager to pursue further study of this regimen, with the hopes of providing metastatic pancreatic cancer patients—whose treatment options are limited—with a new therapeutic approach.”

    Approximately 49,000 Americans are diagnosed with pancreatic cancer every year, and almost 83% of them will eventually die from the illness (American Cancer Society). Pancreatic adenocarcinoma (the most common type of pancreatic cancer) is one of the most aggressive cancers, and more than 80% of patients present with advanced or metastatic disease in which the cancer has already spread to the lymph nodes and/or metastasized to distant sites.