Lead Investigator: Susan Bates, MD, Columbia University Medical Center
Title of Proposal Research: Assessing the tumor growth and decay rates in patients with pancreatic cancer treated with Gemcitabine/Abraxane: Comparing real world data with clinical trial data
Vivli Data Request: 5163
Funding Source: None.
Potential Conflicts of Interest: None.
Summary of the Proposed Research:
Pancreatic cancer remains one of the most difficult-to-treat cancers, in part due to late diagnosis and in part due to chemotherapy refractoriness. In 2017, there were an estimated 53,670 new cases of pancreatic cancer. It is the 3rd leading cause of cancer deaths, with a projected 43,090 deaths in 2017. Most pancreatic cancers are diagnosed beyond the age of 60 years. The incidence rate is greater in blacks than in whites and greater in males than in females. Tobacco use and exposure are associated with an increased risk of pancreatic cancer, and tobacco use has been prevalent in the VA system. While there are two regimens with proven efficacy for pancreatic cancer available to clinicians, patients in the VHA system have co-morbidities particularly related to tobacco and alcohol use, and also often have cardiac, renal and hepatic dysfunction limiting care. They are thus more often treated with gemcitabine/Abraxane due to its greater tolerability. However, there has been no analysis of PDAC outcomes in the VHA system.
Pancreatic cancer remains one of the most difficult-to-treat cancers, in part due to late diagnosis and in part due to resistance to chemotherapy. In 2017, there were an estimated 53,670 new cases of pancreatic cancer. It is the 3rd leading cause of cancer deaths, with a projected 43,090 deaths in 2017. Most pancreatic cancers are diagnosed beyond the age of 60 years. The incidence rate is greater in blacks than in whites and greater in males than in females. Only 8% of people with pancreatic cancers are expected to live 5 years.
A complete surgical resection offers the only prospect of cure, and only 20% of patients have disease that is considered amenable to resection. For the small fraction considered immediately operable, surgical resection followed by adjuvant chemotherapy is demonstrated in randomized clinical trials to increase survival. Other patients have tumors that may become resectable with a good response to chemotherapy, considered ‘neoadjuvant’ therapy. Observational studies have confirmed a beneficial effect on survival and the best therapy in the neoadjuvant setting is unknown. Regimens used in these settings are derived from data obtained in the metastatic setting, and the choice of regimen often depends on the clinician’s impression of the patient’s ability to tolerate that regimen. Thus, demonstration of efficacy in the metastatic setting has implications for treatment across all disease stages. Almost 14,000 patients were enrolled in over 40 randomized trials to prove that these therapies exceeded gemcitabine alone. Ultimately, two regimens were successful – FOLFIRINOX, with an 11-month overall survival in metastatic disease, and gemcitabine/nab-paclitaxel with an 8.6-month overall survival. FOLFIRINOX is generally considered a more difficult regimen to tolerate, particularly in older patients with more comorbidities. As a result the field has seen increasing use of gemcitabine/Abraxane in many settings, including among Veterans with pancreatic cancer.
Our intent is to evaluate gemcitabine/Abraxane in the VHA system. The Veterans Health Administration (VHA) is a nationwide healthcare system that provides care for over 9 million US Veterans enrolled into the VA health care program. U.S. Veterans of military service generally have high rates of co-morbidities, including those due to tobacco and alcohol use. The VHA has the world’s largest common electronic health care record system, with research access hosted on the VA Informatics and Computing Infrastructure (VINCI). We plan to use VINCI data to examine the outcomes of patients with pancreatic cancer in the VHA system. Gemcitabine/Abraxane is widely used in the VHA system and one question that can be asked is whether outcomes in this setting are comparable to those observed in the landmark clinical trial that established Gem/Abraxane as effective in pancreatic cancer, particularly given the increased rates of co-morbidities seen in the VHA patient population. We will perform a retrospective analysis of Veterans treated for pancreatic cancer within the VA system. With an estimated 300 new diagnoses each year in the VHA, we will be able track outcomes for over a decade. We plan to use the CA046 data as a benchmark to validate the VHA Gem/Abraxane data. We will be able to gather co-morbidities, dosing, survival, and CA 19-9 values as a marker of efficacy. We will determine whether Veterans treated with Gem/Abraxane in the VHA systems have comparable outcomes as patients treated in the Celgene CA046 clinical study. We will initially focus on using the CA19-9 values to determine tumor growth rates during treatment, and gather duration of treatment and survival data as well.
Phase III Study of ABI-007(Albumin-bound Paclitaxel) Plus Gemcitabine Versus Gemcitabine in Metastatic Adenocarcinoma of the Pancreas
Sponsor: Celgene Corporation
Study ID: NCT00844649
Sponsor ID: NCT00844649