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New preclinical and clinical studies investigating treatment options for pancreatic cancer patients.


FDA Approves New Treatment for Certain Digestive Tract Cancers
PanCAN articles: Lutathera® Drug Approved for Pancreatic Neuroendocrine Tumors; 5 Key Facts about PNETs
The U.S. Food and Drug Administration approved Lutathera (lutetium Lu 177 dotatate) for the treatment of a type of cancer that affects the pancreas or gastrointestinal tract called gastroenteropancreatic neuroendocrine tumors (GEP-NETs). This is the first time a radioactive drug, or radiopharmaceutical, has been approved for the treatment of GEP-NETs. Lutathera is indicated for adult patients with somatostatin receptor-positive GEP-NETs.
 

PanCAN’s Precision Medicine Results Featured at Major Meeting
GI Cancers Symposium abstracts: Multiomic molecular comparison of primary versus metastatic pancreatic tumors; Molecular and clinical characterization of BRAF mutations in pancreatic ductal adenocarcinomas (PDACs); Introduction of #PancChat: A novel Twitter platform to inform and engage the pancreatic cancer community
Two of the PanCAN-affiliated posters presented at the GI Cancers Symposium relate to the organization’s Know Your Tumor® precision medicine service, prepared in collaboration with the precision medicine company Perthera and research partners at several major institutions. The final poster involving PanCAN that will be presented at this year’s GI Cancers Symposium switches gears to social media – and how Twitter can facilitate disease-specific conversations.


Mismatch-repair Deficiency Predicts Response of Solid Tumors to PD-1 Blockade
Pancreatic Cancer Action Network Latest News blog article: 5 Things to Know About New Drug Keytruda

  • Journal: Science
  • Institution(s): Johns Hopkins, Baltimore, MD, and others
  • Corresponding author(s): Luis Diaz
  • Pancreatic Cancer Action Network-affiliated authors:
    • Dung Le, MD: PI, 2014 Fredman Family Foundation – Research Acceleration Network Grant
    • George Fisher, MD, PhD: member, Scientific & Medical Advisory Board
    • Todd Crocenzi, MD: co- PI, 2014 Fredman Family Foundation – Research Acceleration Network Grant
    • James Eshleman, MD, PhD: recipient, 2011 Innovative Grant
  • Major finding: These data support the hypothesis that the large proportion of mutant neoantigens in mismatch repair-deficient cancers make them sensitive to immune checkpoint blockade, regardless of the cancers’ tissue of origin.

 
 
Association of Distinct Mutational Signatures With Correlates of Increased Immune Activity in Pancreatic Ductal Adenocarcinoma

  • Journal: JAMA Oncology
  • Institution(s): Ontario Institute for Cancer Research, Toronto, Ontario, Canada, and others
  • Corresponding author(s): Steven Gallinger
  • Pancreatic Cancer Action Network-affiliated authors:
    • Gloria Petersen, PhD: recipient, 2017 Early Detection Targeted Grant and member, Scientific & Medical Advisory Board
    • Michael Hollingsworth, PhD: member, Scientific & Medical Advisory Board
  • Major finding: Signature-based subtyping may guide personalized therapy of pancreatic ductal adenocarcinoma in the context of biomarker-driven prospective trials.

 
 
Feasibility Study of Ultrasound Imaging for Stereotactic Body Radiation Therapy with Active Breathing Coordinator in Pancreatic Cancer

  • Journal: Journal of Applied Clinical Medical Physics
  • Institution(s): Johns Hopkins University, Baltimore, MD
  • Corresponding author(s): Kai Ding
  • Pancreatic Cancer Action Network-affiliated author: Joseph Herman, MD, MSc: recipient, 2008 Blum-Kovler – Career Development Award and member, Scientific & Medical Advisory Board
  • Major finding: The authors’ ultrasound system can be potentially used for real-time monitoring during pancreas stereotactic body radiation therapy (SBRT) without compromising planning quality. The phantom study showed high monitoring accuracy of the system, and the volunteer study showed feasibility of the clinical workflow.

 
 
Targeting the Tumor Stroma: The Biology and Clinical Development of Pegylated Recombinant Human Hyaluronidase (PEGPH20)

  • Journal: Current Oncology Reports
  • Institution(s): University of Washington School of Medicine, Seattle, WA, and others
  • Corresponding author(s): William Harris
  • Pancreatic Cancer Action Network-affiliated author: Sunil Hingorani, MD, PhD: recipient, 2017 Celgene Corporation – Precision Medicine Targeted Grant, 2007 Pilot Grant and 2005 Dr. Laurence A. Mack and Roselle Mack – Career Development Award, PI, Precision Promise Clinical Trial Consortium site and member, Scientific and Medical Advisory Board
  • Major finding: Pegylated recombinant human hyaluronidase (PEGPH20) is a novel agent that degrades hyaluronic acid (HA) and normalizes interstitial gel fluid pressure to enhance the delivery of cytotoxic agents.

 
 
Use of Angiotensin System Inhibitors Is Associated with Immune Activation and Longer Survival in Non-Metastatic Pancreatic Ductal Adenocarcinoma

  • Journal: Clinical Cancer Research 
  • Institution(s): Massachusetts General Hospital, Harvard Medical School, Boston, MA, and others
  • Corresponding author(s): Yves Boucher
  • Pancreatic Cancer Action Network-affiliated author: Yves Boucher, PhD: recipient, 2013 Abby Sobrato – Innovative Grant
  • Major finding: In patients with non-metastatic pancreatic ductal adenocarcinoma (PDAC), chronic angiotensin system inhibitor (ASI) use is associated with longer overall survival independently of chemotherapy. The authors’ RNA-Seq analysis suggests that ASI reduce the malignant potential of cancer cells and stimulate the immune microenvironment in primary PDAC.

 
 
Differential and Joint Effects of Metformin and Statins on Overall Survival of Elderly Patients with Pancreatic Adenocarcinoma: A Large Population-based Study

  • Journal: Cancer Epidemiology, Biomarkers & Prevention
  • Institution(s): Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, and others
  • Corresponding author(s): Xiang-Lin Tan
  • Pancreatic Cancer Action Network-affiliated author: Gloria Petersen, PhD: recipient, 2017 Early Detection Targeted Grant and member, Scientific & Medical Advisory Board
  • Major finding: The authors’ findings suggest potential benefits of statins on improving survival among elderly pancreatic ductal adenocarcinoma patients; further prospective studies are warranted to corroborate the putative benefit of statin therapy in pancreatic cancer. Although more studies are needed to confirm our findings, their data add to the body of evidence on potential anti-cancer effects of statins.

 
 
Chemoradiation for Locally Advanced Unresectable Pancreatic Cancer-What Now?
Review of: https://www.ncbi.nlm.nih.gov/pubmed/27139057

  • Journal: JAMA Oncology 
  • Institution(s): Oregon Health & Science University, Portland, OR
  • Corresponding author(s): Gina Vaccaro or Charles Lopez
  • Major finding: Randomized clinical trials to date have failed to demonstrate a clear benefit in locally advanced unresectable pancreatic cancer patients for reasons including underpowered trials, poor accrual, lack of optimal systemic therapy or radiation therapy, and lack of radiation quality control. Moreover, a significant limitation of chemoradiation remains the disease biology itself—namely, the high prevalence of occult metastatic disease, rendering many patients unlikely to benefit from a local therapy approach.

 
 
Delivery of Meaningful Cancer Care: A Retrospective Cohort Study Assessing Cost and Benefit with the ASCO and ESMO Frameworks

  • Journal: The Lancet Oncology 
  • Institution(s): University of Toronto, Toronto, ON, Canada, and others
  • Corresponding author(s): Christopher Booth
  • Major finding: The American Society of Clinical Oncology (ASCO) and the European Society for Medical Oncology (ESMO) have developed frameworks that quantify survival gains in light of toxicity and quality of life to assess the benefits of cancer therapies. The authors applied these frameworks to a cohort of contemporary randomized controlled trials to explore agreement between the two approaches and to assess the relation between treatment benefit and cost. They found that there is only fair correlation between these two major value care frameworks, and negative correlations between framework outputs and drug costs. Delivery of optimal cancer care in a sustainable health system will necessitate future oncologists, investigators, and policy makers to reconcile the disconnect between drug cost and clinical benefit.

 
 
Exosomes Facilitate Therapeutic Targeting of Oncogenic KRAS in Pancreatic Cancer

  • Journal: Nature 
  • Institution(s): University of Texas MD Anderson Cancer Center, Houston, TX, and others
  • Corresponding author(s): Raghu Kalluri
  • Major finding: Treatment with engineered exosomes (known as iExosomes) suppressed cancer in multiple mouse models of pancreatic cancer and significantly increased overall survival. The authors’ results demonstrate an approach for direct and specific targeting of oncogenic KRAS in tumors using iExosomes.

 
 
Co-targeting of MEK and PDGFR/STAT3 Pathways to Treat Pancreatic Ductal Adenocarcinoma

  • Journal: Molecular Cancer Therapeutics 
  • Institution(s): Genentech, South San Francisco, CA, and others
  • Corresponding author(s): Jeff Settleman
  • Major finding: Combination treatment with a MEK inhibitor and the multi-kinase inhibitor ponatinib was effective in targeting pancreatic cancer cells both in monolayer and spheroids by effectively blocking signaling via the PDGFRa and MEK kinases, while also preventing the activation of STAT3- and S6-mediated compensatory feedback loops in cancer cells. These results reveal a combination drug treatment strategy that may be effective in pancreatic cancer.

 


Studies from the ASCO Annual Meeting:

Clinical Trial Shows Experimental Drug’s Ability to Knock Down Pancreatic Cancer’s Defense
ASCO abstract

  • Meeting: 2017 American Society of Clinical Oncology (ASCO) Annual Meeting
  • Institution(s): Fred Hutchinson Cancer Research Center, Seattle, WA, and others
  • Lead author(s): Sunil Hingorani
  • Pancreatic Cancer Action Network-affiliated authors:
    • Sunil Hingorani, MD, PhD: recipient, 2017 Precision Medicine Targeted Grant, 2007 Pilot Grant and 2005 Dr. Laurence A. Mack and Roselle Mack – Career Development Award, PI, Precision Promise Clinical Trial Consortium site and member, Scientific & Medical Advisory Board
    • Andrew Hendifar, MD, MPH: PI, Precision Promise Clinical Trial Consortium site
  • Major finding: Hyaluronan (HA) accumulation in the tumor microenvironment produces elevated tumor pressure, vascular compression, and reduced drug delivery. PEGPH20 degrades HA, increasing the access and therapeutic index of anticancer agents. Randomized Phase II study met both primary endpoints (PFS and TE event rate), with the largest improvement in the secondary endpoint of PFS in HA-High pts. These data support HA as a potential predictive biomarker for patient selection of PEGPH20, currently investigated in the ongoing global Phase III HALO 301 study with PFS and OS as co-primary endpoints.

 
 
Deploying Immunotherapy in Pancreatic Cancer: Defining Mechanisms of Response and Resistance

  • Journal: 2017 ASCO Educational Book
  • Institution(s): University of Pennsylvania, Philadelphia, PA
  • Corresponding author(s): Gregory Beatty
  • Pancreatic Cancer Action Network-affiliated author: Gregory Beatty, MD, PhD: recipient, 2017 Precision Medicine Targeted Grant and 2015 Career Development Award, co-PI, Precision Promise Clinical Trial Consortium site and member, Scientific & Medical Advisory Board
  • Major finding: Overall, the success of immunotherapy in pancreatic ductal adenocarcinoma will most likely rely on strategic combinations of therapies that are informed by well-designed correlative analyses that consider the spatial heterogeneity of immune responses detected in malignant tissues.

 
 
Pancreatic Adenocarcinoma: Improving Prevention and Survivorship

  • Journal: 2017 ASCO Educational Book
  • Institution(s): Cleveland Clinic, Cleveland, OH, and others
  • Corresponding author(s): Davendra Sohal
  • Major finding: The authors focus on current opinions and practices around neoadjuvant therapy, discussing chemotherapy and radiation aspects, and the role of surgical resection.

 


Studies from the ESMO World Congress:

Halozyme Phase 2 Data In Advanced Pancreas Cancer Presented At European Society For Medical Oncology Symposium

  • Meeting: European Society for Medical Oncology’s 19th World Congress on Gastrointestinal Cancer
  • Company: Halozyme Therapeutics, San Diego, CA
  • Lead author(s): Andrew Hendifar, Andrea Bullock
  • Pancreatic Cancer Action Network-affiliated author: Andrew Hendifar, MD, MPH: PI, Precision Promise Clinical Trial Consortium site
  • Major finding: Results from Halozyme Therapeutics Phase 2 randomized, multi-center clinical trial in pancreas cancer patients were shared in two oral presentations at the European Society for Medical Oncology’s 19th World Congress on Gastrointestinal Cancer. As previously reported, the study met its primary efficacy and safety endpoints and the key secondary endpoint of progression-free survival (PFS) in hyaluronan (HA)-High patients. PEGPH20 plus standard chemotherapy of ABRAXANE® (nab-paclitaxel) and gemcitabine improved median PFS by 77 percent over chemotherapy alone in HA-High patients.

 
 
ESMO World GI 2017: Pegilodecakin Plus FOLFOX in Advanced Pancreatic Cancer
ESMO abstract

  • Meeting: European Society for Medical Oncology’s 19th World Congress on Gastrointestinal Cancer
  • Institution(s): David Geffen School of Medicine at UCLA, Santa Monica, CA, and others
  • Lead author(s): J. Randolph Hecht
  • Major finding: Clinical data on an investigational immuno-oncology drug pegilodecakin (PEGylated human interleukin-10, also known as AM0010) was presented by Hecht et al at the ESMO 19th World Congress on Gastrointestinal Cancer in Barcelona, Spain. Pegilodecakin is being evaluated in an ongoing phase I/Ib clinical trial that has enrolled 352 advanced cancer patients and in a phase III clinical trial that is enrolling patients with advanced pancreatic cancer.

 
 
Novocure to Present Three Abstracts on Tumor Treating Fields and Pancreatic Cancer at the European Society for Medical Oncology 19th World Congress on Gastrointestinal Cancer

  • Meeting: European Society for Medical Oncology’s 19th World Congress on Gastrointestinal Cancer
  • Company: Novocure, St. Helier, Jersey
  • Major finding: Novocure announced that the company will present three abstracts studying Tumor Treating Fields (TTFields) in pancreatic cancer at the European Society for Medical Oncology 19th World Congress on Gastrointestinal Cancer on June 28 through July 1 in Barcelona. Among the highlights is an abstract that will outline the trial design for PANOVA-3, Novocure’s phase 3 pivotal study of TTFields with gemcitabine and nab-paclitaxel as a front-line treatment of locally advanced pancreatic cancer.

 


Industry news:

Philips and Memorial Sloan Kettering Cancer Center announce research agreement to jointly develop advanced genome analytics for precision oncology

  • Company: Royal Philips, Amsterdam, Netherlands
  • Major finding: Royal Philips, a global leader in health technology, and Memorial Sloan Kettering Cancer Center, the world’s oldest and largest private cancer center, announced a research collaboration to help improve the understanding of pancreatic cancer and advance precision oncology.

 
 
Intezyne Technologies Granted Orphan Drug Designation for IT-139 in Pancreatic Cancer

  • Company: Intezyne Technologies, Tampa, FL
  • Major finding: Intezyne Technologies, a clinical-stage biopharmaceutical company developing novel anti-cancer therapies, announced that that the Office of Orphan Products Development of the Food and Drug Administration (FDA) has granted Orphan Drug Designation (ODD) to IT-139, the most clinically advanced GRP78 inhibitor in development for solid tumors, for the treatment of pancreatic cancer.

 
 
FibroGen Granted Orphan Drug Designation for Pamrevlumab in the Treatment of Pancreatic Cancer

  • Company: FibroGen, Inc., San Francisco, CA
  • Major finding: FibroGen, Inc., a science-based biopharmaceutical company, announced that the U.S. Food and Drug Administration (FDA) has granted Orphan Drug Designation status to pamrevlumab, the company’s first-in-class antibody, for the treatment of pancreatic cancer. Pamrevlumab (formerly FG-3019) is an investigational therapeutic antibody developed by FibroGen to inhibit the activity of connective tissue growth factor (CTGF), a common factor in chronic fibrotic and proliferative disorders characterized by persistent and excessive scarring that can lead to organ dysfunction and failure.

 

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