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Pancreatic Neoplasms: HELP
Articles by Andrea Wang-Gillam
Based on 48 articles published since 2010
(Why 48 articles?)
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Between 2010 and 2020, A. Wang-Gillam wrote the following 48 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
Pages: 1 · 2
1 Review Trends in Neoadjuvant Approaches in Pancreatic Cancer. 2017

Du, Lingling / Wang-Gillam, Andrea. ·From the Division of Medical Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri. ·J Natl Compr Canc Netw · Pubmed #28784867.

ABSTRACT: Pancreatic cancer (PDAC) is an aggressive tumor type associated with development of micrometastasis at an early stage. In attempt to eradicate disseminated disease, neoadjuvant therapy has been explored in patients with resectable and borderline resectable PDAC. In large retrospective studies, neoadjuvant therapy was associated with better survival compared with upfront surgery. Previously, trials more commonly used radiotherapy (RT) with small doses of chemotherapy as radiosensitizers. Recent studies, however, have incorporated full systemic doses of chemotherapy with or without RT before surgery with the hope of achieving adequate systemic chemotherapy coverage and improving survival. Several phase II trials have shown encouraging clinical benefits using the neoadjuvant approach. Large cooperative group studies are exploring the role of neoadjuvant treatment with newer combination chemotherapy regimens and modern RT techniques, which will provide more evidence regarding the utility of this approach.

2 Review FOLFIRINOX for locally advanced pancreatic cancer: a systematic review and patient-level meta-analysis. 2016

Suker, Mustafa / Beumer, Berend R / Sadot, Eran / Marthey, Lysiane / Faris, Jason E / Mellon, Eric A / El-Rayes, Bassel F / Wang-Gillam, Andrea / Lacy, Jill / Hosein, Peter J / Moorcraft, Sing Yu / Conroy, Thierry / Hohla, Florian / Allen, Peter / Taieb, Julien / Hong, Theodore S / Shridhar, Ravi / Chau, Ian / van Eijck, Casper H / Koerkamp, Bas Groot. ·Department of Surgery, Erasmus University Medical Centre, Rotterdam, Netherlands. · Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA. · Department of Hepatogastroenterology, Antoine Beclère Hospital, Assistance publique-Hôpitaux de Paris, Paris Sud University, Clamart, France. · Department of Hematology-Oncology, Massachusetts General Hospital, Boston, MA, USA. · Department of Radiation Oncology, H Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA. · Department of Hematology and Medical Oncology, Emory University, Atlanta, GA, USA. · Department of Medicine, Washington University School of Medicine, Saint Louis, MO, USA. · Department of Medicine, Yale Cancer Center, Yale School of Medicine, New Haven, CT, USA. · Department of Medicine, Division of Medical Oncology, University of Kentucky-Markey Cancer Center, Lexington, KY, USA. · Department of Medicine, The Royal Marsden National Health Service Foundation Trust, London and Surrey, UK. · Department of Medical Oncology, Institut de Cancérologie de Lorraine and Lorraine University, Vandoeuvre-lès-Nancy, France. · Department of Hematology, Medical Oncology, Hemostasis, Rheumatology and Infectious Diseases, Paracelsus Medical University of Salzburg, Salzburg, Austria. · Department of Gastroenterology and Digestive Oncology, Georges Pompidou European Hospital, Assistance publique-Hôpitaux de Paris, Sorbonne Paris Cité, Paris Descartes University, Cancer Research Personalized Medicine (CARPEM), Paris, France. · Department of Radiation Oncology, Florida Hospital Cancer Institute, Orlando, FL, USA. · Department of Surgery, Erasmus University Medical Centre, Rotterdam, Netherlands. Electronic address: b.grootkoerkamp@erasmusmc.nl. ·Lancet Oncol · Pubmed #27160474.

ABSTRACT: BACKGROUND: 35% of patients with pancreatic cancer have unresectable locally advanced disease at diagnosis. Several studies have examined systemic chemotherapy with FOLFIRINOX (leucovorin and fluorouracil plus irinotecan and oxaliplatin) in patients with locally advanced pancreatic cancer. We aimed to assess the effectiveness of FOLFIRINOX as first-line treatment in this patient population. METHODS: We systematically searched Embase, MEDLINE (OvidSP), Web of Science, Scopus, PubMed Publisher, Cochrane, and Google Scholar from July 1, 1994, to July 2, 2015, for studies of treatment-naive patients of any age who received FOLFIRINOX as first-line treatment of locally advanced pancreatic cancer. Our primary outcome was overall survival. Secondary outcomes were progression-free survival; rates of grade 3 or 4 adverse events; and the proportion of patients who underwent radiotherapy or chemoradiotherapy, surgical resection after FOLFIRINOX, and R0 resection. We evaluated survival outcomes with the Kaplan-Meier method with patient-level data. Grade 3 or 4 adverse events, and the proportion of patients who underwent subsequent radiotherapy or chemoradiotherapy or resection, were pooled in a random-effects model. FINDINGS: We included 13 studies comprising 689 patients, of whom 355 (52%) patients had locally advanced pancreatic cancer. 11 studies, comprising 315 patients with locally advanced disease, reported survival outcomes and were eligible for patient-level meta-analysis. Median overall survival from the start of FOLFIRINOX ranged from 10·0 months (95% CI 4·0-16·0) to 32·7 months (23·1-42·3) across studies with a pooled patient-level median overall survival of 24·2 months (95% CI 21·7-26·8). Median progression-free survival ranged from 3·0 months (95% CI not calculable) to 20·4 months (6·5-34·3) across studies with a patient-level median progression-free survival of 15·0 months (95% 13·8-16·2). In ten studies comprising 490 patients, 296 grade 3 or 4 adverse events were reported (60·4 events per 100 patients). No deaths were attributed to FOLFIRINOX toxicity. The proportion of patients who underwent radiotherapy or chemoradiotherapy ranged from 31% to 100% across studies. In eight studies, 154 (57%) of 271 patients received radiotherapy or chemoradiotherapy after FOLFIRINOX. The pooled proportion of patients who received any radiotherapy treatment was 63·5% (95% CI 43·3-81·6, I(2) 90%). The proportion of patients who underwent surgical resection for locally advanced pancreatic cancer ranged from 0% to 43%. The proportion of patients who had R0 resection of those who underwent resection ranged from 50% to 100% across studies. In 12 studies, 91 (28%) of 325 patients underwent resection after FOLFIRINOX. The pooled proportion of patients who had resection was 25·9% (95% CI 20·2-31·9, I(2) 24%). R0 resection was reported in 60 (74%) of 81 patients. The pooled proportion of patients who had R0 resection was 78·4% (95% CI 60·2-92·2, I(2) 64%). INTERPRETATION: Patients with locally advanced pancreatic cancer treated with FOLFIRINOX had a median overall survival of 24·2 months-longer than that reported with gemcitabine (6-13 months). Future research should assess these promising results in a randomised controlled trial, and should establish which patients might benefit from radiotherapy or chemoradiotherapy or resection after FOLFIRINOX. FUNDING: None.

3 Review Nanoliposomal irinotecan plus fluorouracil and folinic acid: a new treatment option in metastatic pancreatic cancer. 2016

Ur Rehman, Sana Saif / Lim, Kian / Wang-Gillam, Andrea. ·a Division of Oncology, Department of Medicine , Washington University in St. Louis , St. Louis , MO , USA. · b Siteman Cancer Center , Washington University School of Medicine , St. Louis , MO , USA. ·Expert Rev Anticancer Ther · Pubmed #27043737.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) remains a deadly disease with half of patients diagnosed in the metastatic setting. Until recently, patients after progression on front-line gemcitabine-based regimen had no standard second-line option, although flouropyrimidine-based regimens were frequently used in this setting. Encapsulation of chemotherapeutics in liposomal formulation is an effective way of prolonging drug deposition thereby enhancing cytotoxic efficacy. In a large phase III randomized trial on metastatic PDAC patients who progressed after gemcitabine-based chemotherapy, a novel nanoliposome-encapsulated irinotecan (PEP02, MM-398, nal-IRI, Onivyde, Merrimack, Boston, US) plus fluorouracil and folinic acid demonstrated a significant survival advantage compared to fluorouracil and folinic acid alone. This pivotal study led to the recent FDA approval of nanoliposomal irinotecan in patients with metastatic PDAC. In this article, we will review the literature regarding existing treatment options for metastatic PDAC, focusing specifically on nanoliposomal irinotecan in the clinical setting and its future implication.

4 Review Perioperative Therapy for Surgically Resectable Pancreatic Adenocarcinoma. 2015

Du, Lingling / DeFoe, Melissa / Ruzinova, Marianna B / Olsen, Jeffrey R / Wang-Gillam, Andrea. ·Division of Oncology, Department of Internal Medicine, Washington University School of Medicine, 660 South Euclid Avenue, St Louis, MO 63110, USA; Division of Medical Oncology, Alvin J. Siteman Cancer Center, Washington University School of Medicine, 660 South Euclid Avenue, St Louis, MO 63110, USA. · Department of Internal Medicine, Washington University School of Medicine, 660 South Euclid Avenue, St Louis, MO 63110, USA. · Department of Pathology and Immunology, Washington University School of Medicine, 660 South Euclid Avenue, St Louis, MO 63110, USA. · Department of Radiation Oncology, Washington University School of Medicine, 660 South Euclid Avenue, St Louis, MO 63110, USA. · Division of Oncology, Department of Internal Medicine, Washington University School of Medicine, 660 South Euclid Avenue, St Louis, MO 63110, USA; Division of Medical Oncology, Alvin J. Siteman Cancer Center, Washington University School of Medicine, 660 South Euclid Avenue, St Louis, MO 63110, USA. Electronic address: awang@dom.wustl.edu. ·Hematol Oncol Clin North Am · Pubmed #26226906.

ABSTRACT: It is estimated that 10% to 20% of patients with pancreatic cancer present with resectable disease. Although surgery offers curative intent, the median survival after curative resection is less than 2 years. To improve clinical outcomes in this patient population, clinical studies have investigated the role of perioperative therapy, including neoadjuvant and adjuvant treatment in resectable pancreatic cancer. The role of adjuvant therapy has been well established by large randomized phase III studies, whereas benefit of the neoadjuvant approach remains inconclusive. Here, we review various treatment modalities and their clinical benefits in resectable pancreatic cancer.

5 Review Advanced pancreatic adenocarcinoma: a review of current treatment strategies and developing therapies. 2015

Teague, Andrea / Lim, Kian-Huat / Wang-Gillam, Andrea. ·Division of Oncology, Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO, USA. · Division of Oncology, Department of Medicine, Campus Box 8056, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA. ·Ther Adv Med Oncol · Pubmed #25755680.

ABSTRACT: Pancreatic adenocarcinoma is one of the deadliest solid malignancies. A large proportion of patients are diagnosed with locally advanced or metastatic disease at the time of presentation and, unfortunately, this severely limits the number of patients who can undergo surgical resection, which offers the only chance for cure. Recent therapeutic advances for patients with advanced pancreatic cancer have extended overall survival, but prognosis still remains grim. Given that traditional chemotherapy is ineffective in curing advanced pancreatic adenocarcinoma, current research is taking a multidirectional approach in the hopes of developing more effective treatments. This article reviews the major clinical trial data that is the basis for the current chemotherapy regimens used as first- and second-line treatments for advanced pancreatic adenocarcinoma. We also review the current ongoing clinical trials, which include the use of agents targeting the oncogenic network signaling of K-Ras, agents targeting the extracellular matrix, and immune therapies.

6 Review Changing the way we do business: recommendations to accelerate biomarker development in pancreatic cancer. 2013

Tempero, Margaret A / Klimstra, David / Berlin, Jordan / Hollingsworth, Tony / Kim, Paula / Merchant, Nipun / Moore, Malcolm / Pleskow, Doug / Wang-Gillam, Andrea / Lowy, Andrew M. ·Pancreas Center, University of California San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, CA 94115, USA. mtempero@medicine.ucsf.edu ·Clin Cancer Res · Pubmed #23344262.

ABSTRACT: Pancreatic ductal adenocarcinoma is the most aggressive of all epithelial malignancies. In contrast to the favorable trends seen in most other common malignancies, the five-year survival of patients with this disease remains only 6%, a statistic that has changed minimally for decades. Only two drugs have been approved by the U.S. Food and Drug Administration (FDA) for use in pancreatic cancer in the last 15 years, and there are no established strategies for early detection.

7 Review Supportive care considerations during concurrent chemoradiotherapy for pancreatic adenocarcinoma: lessons learned from clinical experience. 2013

Wang-Gillam, Andrea / Abrams, Ross A / Posner, Mitchell C / Pisters, Peter W T / Picozzi, Vincent J. ·*Division of Hematology-Oncology, Siteman Cancer Center, Washington University in St. Louis School of Medicine, St. Louis, MO †Department of Radiation Oncology, Rush University Medical Center ‡Department of Surgery, University of Chicago Medical Center, Chicago, IL §Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX ∥Cancer and Digestive Diseases Institutes, Virginia Mason Medical Center, Seattle, WA. ·Am J Clin Oncol · Pubmed #22237148.

ABSTRACT: Concurrent chemotherapy and radiotherapy (chemoradiotherapy) for the management of pancreatic adenocarcinoma in either adjuvant or locally regional advanced settings produces predictable acute toxicities that are proportional in severity to the intensity and type of systemic therapy and to the parameters of radiotherapy. In addition, relevant to the adjuvant setting, surgery for pancreatic cancer often produces physiologic alterations that may impact a patient's ability to tolerate chemoradiotherapy. Failures to anticipate, monitor, and proactively manage the effects of surgery and toxicities of chemoradiotherapy can result in the need for unplanned treatment interruptions and/or inability to complete all planned therapy. In this review, complications of pancreatic cancer itself and of pancreatic resection as well as toxicities of chemoradiotherapy are delineated, and approaches to their management before, during, and after chemoradiotherapy are presented. Planning for the treatment of side effects before the anticancer therapy begins facilitates therapy administration and improves patient tolerance.

8 Review Neoadjuvant therapy of pancreatic cancer: the emerging paradigm? 2012

Lim, Kian-Huat / Chung, Eugene / Khan, Adeel / Cao, Dengfeng / Linehan, David / Ben-Josef, Edgar / Wang-Gillam, Andrea. ·Medical Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA. ·Oncologist · Pubmed #22250057.

ABSTRACT: Pancreatic cancer remains one of the deadliest cancers due to difficulty in early diagnosis and its high resistance to chemotherapy and radiation. It is now clear that even patients with potentially resectable disease require multimodality treatment including chemotherapy and/or radiation to improve resectability and reduce recurrence. Tremendous efforts are currently being invested in refining preoperative staging to identify optimal surgical candidates, and also in developing various neoadjuvant or adjuvant regimens to improve surgical outcome. Although at present no studies have been done to directly compare the benefit of neoadjuvant versus adjuvant approaches, accumulating evidence suggests that the neoadjuvant approach is probably beneficial for a subset of the patient population, particularly those with borderline resectable disease in which complete surgical resection is almost certainly unachievable. In this article, we review the literature and rationales of neoadjuvant chemotherapy and chemoradiation, as well as their potential limitations and caveats. We also review the pathological findings following neoadjuvant therapies, and potential surgical complications that may be associated with neoadjuvant therapies.

9 Review Myeloid-derived suppressor cells: general characteristics and relevance to clinical management of pancreatic cancer. 2011

Goedegebuure, P / Mitchem, J B / Porembka, M R / Tan, M C B / Belt, B A / Wang-Gillam, A / Gillanders, W E / Hawkins, W G / Linehan, D C. ·Department of Surgery and Alvin J. Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO 63110, USA. goedegep@wustl.edu ·Curr Cancer Drug Targets · Pubmed #21599634.

ABSTRACT: Recent studies describe a heterogeneous population of cells of the myeloid lineage, termed myeloid derived suppressor cells (MDSC), which are observed with increased prevalence in the peripheral blood and tumor microenvironment of cancer patients, including pancreatic cancer. Accumulation of MDSC in the peripheral circulation has been related to extent of disease, and correlates with stage. MDSC have primarily been implicated in promoting tumor growth by suppressing antitumor immunity. There is also compelling evidence MDSC are also involved in angiogenesis and metastatic spread. Two main subsets of MDSC have been identified in cancer patients: a monocytic subset, characterized by expression of CD14, and a granulocytic subset characterized by expression of CD15. Both subsets of MDSC actively suppress host immunity through a variety of mechanisms including production of reactive oxygen species and arginase. Just as in humans, accumulation of monocytic and granulocytic MDSC has been noted in the bone marrow, spleen, peripheral circulation, and tumors of tumor bearing mice. Successful targeting of MDSC in mice is associated with improved immune responses, delayed tumor growth, improved survival, and increased efficacy of vaccine therapy. By further elucidating mechanisms of MDSC recruitment and maintenance in the tumor environment, strategies could be developed to reverse immune tolerance to tumor. We discuss here what is currently known about MDSC as well as some potential strategies targeting MDSC in the context of our work on pancreatic cancer and recent literature. Due to the number of new reports on MDSC, the most pertinent ones have been selected.

10 Clinical Trial Survival with nal-IRI (liposomal irinotecan) plus 5-fluorouracil and leucovorin versus 5-fluorouracil and leucovorin in per-protocol and non-per-protocol populations of NAPOLI-1: Expanded analysis of a global phase 3 trial. 2018

Chen, Li-Tzong / Siveke, Jens T / Wang-Gillam, Andrea / Li, Chung-Pin / Bodoky, György / Dean, Andrew P / Shan, Yan-Shen / Jameson, Gayle S / Macarulla, Teresa / Lee, Kyung-Hun / Cunningham, David / Blanc, Jean-Frédéric / Chiu, Chang-Fang / Schwartsmann, Gilberto / Braiteh, Fadi S / Mamlouk, Khalid / Belanger, Bruce / de Jong, Floris A / Hubner, Richard A. ·National Institute of Cancer Research, National Health Research Institutes (NHRI), 367 Sheng-Li Road, Tainan 704, Taiwan; Department of Internal Medicine, National Cheng Kung University Hospital, National Cheng Kung University, No. 138, Sheng-Li Road, Tainan 704, Taiwan. Electronic address: leochen@nhri.org.tw. · Division of Solid Tumor Translational Oncology, West German Cancer Center, University Hospital Essen, Hufelandstrasse 55, 45147 Essen, Germany; German Cancer Consortium (DKTK, Partner Site Essen) and German Cancer Research Center, DKFZ, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany. · Division of Oncology, Washington University in St. Louis, 660 South Euclid Ave, St. Louis, MO 63110, USA. · Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, No. 201, Section 2, Shipai Rd, Beitou District, Taipei 112, Taiwan; National Yang-Ming University School of Medicine, No. 155, Section 2, Linong St, Beitou District, Taipei 112, Taiwan. · Department of Oncology, Szent László Hospital, Albert Flórián út 5, 1097 Budapest, Hungary. · St. John of God Hospital, 12 Salvado Rd, Subiaco, WA 6008, Australia. · Department of Surgery, National Cheng Kung University Hospital, No. 138, Shengli Rd, North District, Tainan 704, Taiwan. · Virginia G. Piper Cancer Center at HonorHealth/TGen, 10460N 92(nd) St #206, Scottsdale, AZ 85258, USA. · Vall d'Hebron University Hospital (HUVH), Passeig de la Vall d'Hebron, 119-129, 08035 Barcelona, Spain; Vall d'Hebron Institute of Oncology (VHIO), Centro Cellex, Calle Natzaret, 115-117, 08035 Barcelona, Spain. · Department of Internal Medicine and Cancer Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, 1 Gwanak-ro, Daehak-dong, Gwanak-gu, Seoul 03080, South Korea. · The Royal Marsden Hospital NHS Foundation Trust, 203 Fulham Rd, Chelsea, SW3 6JJ London, UK; The Royal Marsden Hospital NHS Foundation Trust (Surrey), Downs Rd, Sutton, SM2 5PT Surrey, UK. · Pôle ADEN, Hôpital Haut-Lévêque, CHU Bordeaux, 33075 Bordeaux, France. · China Medical University Hospital, No. 2, Yuh-Der Rd, Taichung 404, Taiwan. · Federal University of Rio Grande do Sul, Av. Paulo Gama, 110 - Farroupilha, Porto Alegre, RS 90040-060, Brazil. · Comprehensive Cancer Centers of Nevada, University of Nevada School of Medicine, 3730 S Eastern Ave, Las Vegas, NV 89169, USA. · Ipsen Bioscience, Inc., 650 East Kendall St, Cambridge, MA 02142, USA. · Shire, Zählerweg 10, 6300 Zug, Switzerland. · Department of Medical Oncology, The Christie Hospital NHS Foundation Trust, 550 Wilmslow Rd, M20 4BX Manchester, UK. ·Eur J Cancer · Pubmed #30414528.

ABSTRACT: BACKGROUND: In the phase 3 randomised NAPOLI-1 clinical study, a 45% increase in median overall survival (OS) was shown with liposomal irinotecan, 5-fluorouracil and leucovorin (nal-IRI+5-FU/LV) versus 5-FU/LV in patients with metastatic pancreatic cancer progressing after gemcitabine-based therapy. Here, we report data from a pre-specified, expanded analysis of outcomes in the per-protocol (PP) population. MATERIALS AND METHODS: The PP population comprised patients receiving ≥80% of planned treatment during the first 6 weeks, with no major protocol violations. A post-hoc analysis of the non-PP population was also performed. RESULTS: For PP patients, median OS was 8.9 (95% confidence interval: 6.4-10.5) months with nal-IRI+5-FU/LV (n = 66) vs 5.1 (4.0-7.2) months with 5-FU/LV (n = 71; unstratified hazard ratio [HR] 0.57, p = 0.011). For non-PP patients, it was 4.4 (3.3-5.3) months with nal-IRI+5-FU/LV (n = 51) vs 2.8 (1.7-3.2) months with 5-FU/LV (n = 48; unstratified HR 0.64, p = 0.0648). CONCLUSION: A statistically significant survival advantage was observed with nal-IRI+5-FU/LV vs 5-FU/LV in the PP patient population.

11 Clinical Trial HALO 202: Randomized Phase II Study of PEGPH20 Plus Nab-Paclitaxel/Gemcitabine Versus Nab-Paclitaxel/Gemcitabine in Patients With Untreated, Metastatic Pancreatic Ductal Adenocarcinoma. 2018

Hingorani, Sunil R / Zheng, Lei / Bullock, Andrea J / Seery, Tara E / Harris, William P / Sigal, Darren S / Braiteh, Fadi / Ritch, Paul S / Zalupski, Mark M / Bahary, Nathan / Oberstein, Paul E / Wang-Gillam, Andrea / Wu, Wilson / Chondros, Dimitrios / Jiang, Ping / Khelifa, Sihem / Pu, Jie / Aldrich, Carrie / Hendifar, Andrew E. ·Sunil R. Hingorani, Fred Hutchinson Cancer Research Center · William P. Harris, University of Washington, School of Medicine, Seattle, WA · Lei Zheng, Johns Hopkins University School of Medicine, Baltimore, MD · Andrea J. Bullock, Beth Israel Deaconess Medical Center, Boston, MA · Tara E. Seery, Chan Soon-Shiong Institute for Medicine, El Segundo · Darren S. Sigal, Scripps Cancer Center, La Jolla · Wilson Wu, Dimitrios Chondros, and Ping Jiang, Halozyme Therapeutics, San Diego · Andrew E. Hendifar, Cedars-Sinai Medical Center and Samuel Oschin Cancer Center, Los Angeles, CA · Fadi Braiteh, Comprehensive Cancer Centers of Nevada, Las Vegas, NV · Paul S. Ritch, Froedtert Hospital and Medical College of Wisconsin, Milwaukee, WI · Mark M. Zalupski, University of Michigan, Ann Arbor, MI · Nathan Bahary, University of Pittsburgh Medical Center Cancer Pavilion, Pittsburgh, PA · Paul E. Oberstein, Columbia University Medical Center, New York, NY · Andrea Wang-Gillam, Washington University, St Louis, MO · and Sihem Khelifa, Jie Pu, and Carrie Aldrich, Ventana Medical Systems, Tucson, AZ. ·J Clin Oncol · Pubmed #29232172.

ABSTRACT: Purpose Metastatic pancreatic ductal adenocarcinoma is characterized by excessive hyaluronan (HA) accumulation in the tumor microenvironment, elevating interstitial pressure and impairing perfusion. Preclinical studies demonstrated pegvorhyaluronidase alfa (PEGPH20) degrades HA, thereby increasing drug delivery. Patients and Methods Patients with previously untreated metastatic pancreatic ductal adenocarcinoma were randomly assigned to treatment with PEGPH20 plus nab-paclitaxel/gemcitabine (PAG) or nab-paclitaxel/gemcitabine (AG). Tumor HA levels were measured retrospectively using a novel affinity histochemistry assay. Primary end points were progression-free survival (PFS; overall) and thromboembolic (TE) event rate. Secondary end points included overall survival, PFS by HA level, and objective response rate. An early imbalance in TE events in the PAG arm led to a clinical hold; thereafter, patients with TE events were excluded and enoxaparin prophylaxis was initiated. Results A total of 279 patients were randomly assigned; 246 had HA data; 231 were evaluable for efficacy; 84 (34%) had HA-high tumors (ie, extracellular matrix HA staining ≥ 50% of tumor surface at any intensity). PFS was significantly improved with PAG treatment overall (hazard ratio [HR], 0.73; 95% CI, 0.53 to 1.00; P = .049) and for patients with HA-high tumors (HR, 0.51; 95% CI, 0.26 to 1.00; P = .048). In patients with HA-high tumors (PAG v AG), the objective response rate was 45% versus 31%, and median overall survival was 11.5 versus 8.5 months (HR, 0.96; 95% CI, 0.57 to 1.61). The most common treatment-related grade 3/4 adverse events with significant differences between arms (PAG v AG) included muscle spasms (13% v 1%), neutropenia (29% v 18%), and myalgia (5% v 0%). TE events were comparable after enoxaparin initiation (14% PAG v 10% AG). Conclusion This study met its primary end points of PFS and TE event rate. The largest improvement in PFS was observed in patients with HA-high tumors who received PAG. A similar TE event rate was observed between the treatment groups in stage 2 of the trial.

12 Clinical Trial Quality-adjusted survival with combination nal-IRI+5-FU/LV vs 5-FU/LV alone in metastatic pancreatic cancer patients previously treated with gemcitabine-based therapy: a Q-TWiST analysis. 2017

Pelzer, Uwe / Blanc, Jean-Frédéric / Melisi, Davide / Cubillo, Antonio / Von Hoff, Daniel D / Wang-Gillam, Andrea / Chen, Li-Tzong / Siveke, Jens T / Wan, Yin / Solem, Caitlyn T / Botteman, Marc F / Yang, Yoojung / de Jong, Floris A / Hubner, Richard A. ·Department of Hematology/Oncology/Tumorimmunology, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany. · Service d'Hépato-Gastroentérologie et Oncologie Digestive, Hôpital Haut-Lévêque, CHU de Bordeaux, Inserm UMR 1053, Université de Bordeaux, Bordeaux, France. · Digestive Molecular Clinical Oncology Unit, University of Verona, Piazzale L.A. Scuro, 10, 37134 Verona, Italy. · Servicio de Oncologia Médica, Centro Integral Oncológico Clara Campal (CIOCC), Hospital Universitario Madrid Sanchinarro, Calle Oña, 10, 28050 Madrid, Spain. · Virginia G. Piper Cancer Center at HonorHealth/TGen, 10460N 92nd St #206, Scottsdale, AZ 85258, USA. · Division of Oncology, Washington University in St Louis, 660 South Euclid Avenue, St Louis, MO 63110, USA. · National Institute of Cancer Research, National Health Research Institutes, 2F, No. 367, Sheng-Li Road, Tainan 70456, Taiwan. · Division of Solid Tumor Translational Oncology, DKTK Partner Site Essen, West German Cancer Center, University Hospital Essen, Hufelandstrasse 55, 45147 Essen, Germany. · German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Heidelberg, Germany. · Pharmerit International, 4350 East-West Hwy #430, Bethesda, MD 20814, USA. · Shire, Plc, 650 East Kendal St, Cambridge, MA 02142, USA. · Department of Global Medical Affairs Oncology, Shire GmbH, Zählerweg 10, 6300 Zug, Switzerland. · Department of Medical Oncology, Christie Hospital NHS Foundation Trust, 550 Wilmslow Rd, Manchester M20 4BX, UK. ·Br J Cancer · Pubmed #28350787.

ABSTRACT: BACKGROUND: In the NAPOLI-1 Phase 3 trial, nal-IRI+5-fluorouracil and leucovorin (5-FU/LV) significantly improved median overall survival (6.1 vs 4.2 months, P=0.012) and progression-free survival (3.1 vs 1.5 months, P=0.0001) vs 5-FU/LV alone in metastatic pancreatic adenocarcinoma patients previously treated with gemcitabine-based therapy. This analysis evaluated between treatment differences in quality-adjusted time without symptoms of disease progression or toxicity (Q-TWiST). METHODS: Overall survival was partitioned into time with grade ⩾3 toxicity (TOX), disease progression (REL), and time without disease progression symptoms or grade ⩾3 toxicity (TWiST). Mean Q-TWiST was calculated by weighting time spent by a utility of 1.0 for TWiST and 0.5 for TOX and REL. In threshold analyses, utility for TOX and REL were varied from 0.0 to 1.0. RESULTS: Patients in nal-IRI+5-FU/LV (n=117) vs 5-FU/LV (n=119) had significantly more mean time in TWiST (3.4 vs 2.4 months) and TOX (1.0 vs 0.3 months) but similar REL (2.5 vs 2.7 months). In the base case, nal-IRI+5-FU/LV patients had 1.3 months (95% CI, 0.4-2.1; 5.1 vs 3.9) greater Q-TWiST (threshold analyses range: 0.9-1.6 months). CONCLUSIONS: Within NAPOLI-1, nal-IRI+5-FU/LV resulted in statistically significant and clinically meaningful gains in quality-adjusted survival vs 5-FU/LV alone.

13 Clinical Trial Effect of Selumetinib and MK-2206 vs Oxaliplatin and Fluorouracil in Patients With Metastatic Pancreatic Cancer After Prior Therapy: SWOG S1115 Study Randomized Clinical Trial. 2017

Chung, Vincent / McDonough, Shannon / Philip, Philip A / Cardin, Dana / Wang-Gillam, Andrea / Hui, Laifong / Tejani, Mohamedtaki A / Seery, Tara E / Dy, Irene A / Al Baghdadi, Tareq / Hendifar, Andrew E / Doyle, L Austin / Lowy, Andrew M / Guthrie, Katherine A / Blanke, Charles D / Hochster, Howard S. ·City of Hope National Medical Center, Duarte, California. · SWOG Statistical Center, Fred Hutchinson Cancer Research Center, Seattle, Washington. · Karmanos Cancer Institute, Wayne State University, Detroit, Michigan. · Vanderbilt University Medical Center, Nashville, Tennessee. · Washington University in St Louis, St Louis, Missouri. · Kaiser Permanente NCORP, Sacramento, California. · University of Rochester, Rochester, New York. · University of California, Irvine, Orange. · Crossroads Cancer Center/Heartland NCORP, Effingham, Illinois. · St Joseph Mercy Hospital/Michigan CRC NCORP, Ann Arbor. · Cedars-Sinai Medical Center, Los Angeles, California. · Cancer Therapy Evaluation Program, National Cancer Institute, Bethesda, Maryland. · University of California, San Diego, La Jolla. · SWOG Group Chair's Office/Knight Cancer Institute, Oregon Health and Science University, Portland. · Yale Cancer Center, New Haven, Connecticut. ·JAMA Oncol · Pubmed #27978579.

ABSTRACT: Importance: KRAS mutations are common in pancreatic cancer, but directly targeting the KRAS protein has thus far been unsuccessful. The aim of this trial was to block the MEK and PI3K/AKT pathways downstream of the KRAS protein as an alternate treatment strategy to slow cancer growth and prolong survival. This was the first cooperative group trial to evaluate this strategy using molecularly targeted oral combination therapy for the treatment of chemotherapy-refractory pancreatic cancer. Objective: To compare selumetinib and MK-2206 vs modified FOLFOX (mFOLFOX) in patients with metastatic pancreatic cancer for whom gemcitabine-based therapy had failed. Design, Setting, and Participants: SWOG S1115 was a randomized phase 2 clinical trial. Between September 2012 and May 2014, 137 patients with metastatic pancreatic adenocarcinoma for whom gemcitabine-based chemotherapy had failed were randomized to selumetinib plus MK-2206 or mFOLFOX. Patients were randomized in a 1:1 fashion and stratified according to duration of prior systemic therapy and presence of liver metastases. Interventions: Patients received selumetinib 100 mg orally per day plus MK-2206 135 mg orally once per week or mFOLFOX (oxaliplatin, 85 mg/m2 intravenous, and fluorouracil, 2400 mg/m2 intravenous infusion over 46-48 hours) on days 1 and 15 of a 28-day cycle. Main Outcomes and Measures: The primary end point of the study was overall survival. Secondary objectives included evaluating toxic effects, objective tumor response, and progression-free survival. Results: There were 58 patients in the selumetinib plus MK-2206 (experimental) arm (60% male; median [range] age, 69 [54-88] years) and 62 patients in the mFOLFOX arm (35% male; median [range] age, 65 [34-82] years). In the experimental arm, median overall survival was shorter (3.9 vs 6.7 months; HR, 1.37; 95% CI, 0.90-2.08; P = .15), as was median progression-free survival (1.9 vs 2.0 months; HR, 1.61; 95% CI, 1.07-2.43; P = .02). One vs 5 patients had a partial response and 12 vs 14 patients had stable disease in the experimental arm vs mFOLFOX arm. Grade 3 or higher toxic effects were observed in 39 patients treated with selumetinib and MK-2206 vs 23 patients treated with mFOLFOX. More patients in the experimental arm discontinued therapy due to adverse events (13 vs 7 patients). Conclusions and Relevance: Dual targeting of the MEK and PI3K/AKT pathways downstream of KRAS by selumetinib plus MK-2206 did not improve overall survival in patients with metastatic pancreatic adenocarcinoma for whom gemcitabine-based chemotherapy had failed. This was the first randomized prospective evaluation of mFOLFOX in the US population that showed comparable results to CONKO-003 and PANCREOX. Trial Registration: clinicaltrials.gov Identifier: NCT01658943.

14 Clinical Trial Targeting tumour-associated macrophages with CCR2 inhibition in combination with FOLFIRINOX in patients with borderline resectable and locally advanced pancreatic cancer: a single-centre, open-label, dose-finding, non-randomised, phase 1b trial. 2016

Nywening, Timothy M / Wang-Gillam, Andrea / Sanford, Dominic E / Belt, Brian A / Panni, Roheena Z / Cusworth, Brian M / Toriola, Adetunji T / Nieman, Rebecca K / Worley, Lori A / Yano, Motoyo / Fowler, Kathryn J / Lockhart, A Craig / Suresh, Rama / Tan, Benjamin R / Lim, Kian-Huat / Fields, Ryan C / Strasberg, Steven M / Hawkins, William G / DeNardo, David G / Goedegebuure, S Peter / Linehan, David C. ·Department of Surgery, Washington University School of Medicine, Saint Louis, MO, USA; Alvin J Siteman Cancer Center, Washington University School of Medicine, Saint Louis, MO, USA. · Division of Oncology, Washington University School of Medicine, Saint Louis, MO, USA; Alvin J Siteman Cancer Center, Washington University School of Medicine, Saint Louis, MO, USA. · Department of Surgery, Washington University School of Medicine, Saint Louis, MO, USA. · Department of Surgery, University of Rochester Medical Center, Rochester, NY, USA; Center for Tumor Immunology, University of Rochester Medical Center, Rochester, NY, USA; Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, NY, USA. · Department of Surgery, Washington University School of Medicine, Saint Louis, MO, USA; Division of Public Health Sciences, Washington University School of Medicine, Saint Louis, MO, USA; Alvin J Siteman Cancer Center, Washington University School of Medicine, Saint Louis, MO, USA. · Mallinckrodt Institute of Radiology, Washington University School of Medicine, Saint Louis, MO, USA; Alvin J Siteman Cancer Center, Washington University School of Medicine, Saint Louis, MO, USA. · Division of Oncology, Washington University School of Medicine, Saint Louis, MO, USA; Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, MO, USA; Alvin J Siteman Cancer Center, Washington University School of Medicine, Saint Louis, MO, USA. · Department of Surgery, University of Rochester Medical Center, Rochester, NY, USA; Center for Tumor Immunology, University of Rochester Medical Center, Rochester, NY, USA; Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, NY, USA. Electronic address: david_linehan@urmc.rochester.edu. ·Lancet Oncol · Pubmed #27055731.

ABSTRACT: BACKGROUND: In pancreatic ductal adenocarcinoma, the CCL2-CCR2 chemokine axis is used to recruit tumour-associated macrophages for construction of an immunosuppressive tumour microenvironment. This pathway has prognostic implications in pancreatic cancer, and blockade of CCR2 restores anti-tumour immunity in preclinical models. We aimed to establish the safety, tolerability, and recommended phase 2 oral dose of the CCR2 inhibitor PF-04136309 in combination with FOLFIRINOX chemotherapy (oxaliplatin and irinotecan plus leucovorin and fluorouracil). METHODS: We did this open-label, dose-finding, non-randomised, phase 1b study at one centre in the USA. We enrolled treatment-naive patients aged 18 years or older with borderline resectable or locally advanced biopsy-proven pancreatic ductal adenocarcinoma, an Eastern Cooperative Oncology Group performance status of 1 or less, measurable disease as defined by Response Evaluation Criteria in Solid Tumors version 1.1, and normal end-organ function. Patients were allocated to receive either FOLFIRINOX alone (oxaliplatin 85 mg/m(2), irinotecan 180 mg/m(2), leucovorin 400 mg/m(2), and bolus fluorouracil 400 mg/m(2), followed by 2400 mg/m(2) 46-h continuous infusion), administered every 2 weeks for a total of six treatment cycles, or in combination with oral PF-04136309, administered at a starting dose of 500 mg twice daily in a standard 3 + 3 dose de-escalation design. Both FOLFIRINOX and PF-04136309 were simultaneously initiated with a total treatment duration of 12 weeks. The primary endpoints were the safety, tolerability, and recommended phase 2 dose of PF-04136309 plus FOLFIRINOX, with an expansion phase planned at the recommended dose. We analysed the primary outcome by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01413022. RESULTS: Between April 19, 2012, and Nov 12, 2014, we treated 47 patients with FOLFIRINOX alone (n=8) or with FOLFIRINOX plus PF-04136309 (n=39). One patient had a dose-limiting toxic effect in the dose de-escalation group receiving FOLFIRINOX plus PF-04136309 at 500 mg twice daily (n=6); this dose was established as the recommended phase 2 dose. We pooled patients in the expansion-phase group (n=33) with those in the dose de-escalation group that received PF-04136309 at the recommended phase 2 dose for assessment of treatment-related toxicity. Six (75%) of the eight patients receiving FOLFIRINOX alone were assessed for treatment toxicity, after exclusion of two (25%) patients due to insurance coverage issues. The median duration of follow-up for treatment toxicity was 72·0 days (IQR 49·5-89·0) in the FOLFIRINOX alone group and 77·0 days (70·0-90·5) in the FOLFIRINOX plus PF-04136309 group. No treatment-related deaths occurred. Two (5%) patients in the FOLFIRINOX plus PF-04136309 group stopped treatment earlier than planned due to treatment-related toxic effects. Grade 3 or higher adverse events reported in at least 10% of the patients receiving PF-04136309 included neutropenia (n=27), febrile neutropenia (n=7), lymphopenia (n=4), diarrhoea (n=6), and hypokalaemia (n=7). Grade 3 or higher adverse events reported in at least 10% of patients receiving FOLFIRINOX alone were neutropenia (n=6), febrile neutropenia (n=1), anaemia (n=2), lymphopenia (n=1), diarrhoea (n=2), hypoalbuminaemia (n=1), and hypokalaemia (n=3). Therapy was terminated because of treatment-related toxicity in one (17%) of the six patients receiving FOLFIRINOX alone. 16 (49%) of 33 patients receiving FOLFIRINOX plus PF-04136309 who had undergone repeat imaging achieved an objective tumour response, with local tumour control achieved in 32 (97%) patients. In the FOLFIRINOX alone group, none of the five patients with repeat imaging achieved an objective response, although four (80%) of those patients achieved stable disease. INTERPRETATION: CCR2-targeted therapy with PF-04136309 in combination with FOLFIRINOX is safe and tolerable. FUNDING: Washington University-Pfizer Biomedical Collaborative.

15 Clinical Trial Nanoliposomal irinotecan with fluorouracil and folinic acid in metastatic pancreatic cancer after previous gemcitabine-based therapy (NAPOLI-1): a global, randomised, open-label, phase 3 trial. 2016

Wang-Gillam, Andrea / Li, Chung-Pin / Bodoky, György / Dean, Andrew / Shan, Yan-Shen / Jameson, Gayle / Macarulla, Teresa / Lee, Kyung-Hun / Cunningham, David / Blanc, Jean F / Hubner, Richard A / Chiu, Chang-Fang / Schwartsmann, Gilberto / Siveke, Jens T / Braiteh, Fadi / Moyo, Victor / Belanger, Bruce / Dhindsa, Navreet / Bayever, Eliel / Von Hoff, Daniel D / Chen, Li-Tzong / Anonymous2510850. ·Washington University School of Medicine, St Louis, MO, USA. · Division of Gastroenterology and Hepatology, Taipei Veterans General Hospital and National Yang-Ming University School of Medicine, Taipei, Taiwan. · St László Teaching Hospital, Budapest, Hungary. · St John of God Hospital, Subiaco, WA, Australia. · National Cheng Kung University Hospital, National Cheng Kung University, Tainan, Taiwan. · TGen, Phoenix, and HonorHealth, Scottsdale, AZ, USA. · Vall d'Hebron University Hospital (HUVH) and Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain. · Seoul National University Hospital, Seoul, South Korea. · The Royal Marsden Hospital, London, UK. · Hôpital Saint-André, Bordeaux, France. · The Christie NHS Foundation Trust, Manchester, UK. · China Medical University Hospital, Taichung, Taiwan. · Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil. · Klinikum rechts der Isar der T U München, Munich, Germany. · Comprehensive Cancer Centers of Nevada, Las Vegas, NV, USA. · Merrimack Pharmaceuticals, Cambridge, MA, USA. · National Institute of Cancer Research, National Health Research Institutes, Tainan, and Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; National Cheng Kung University Hospital, National Cheng Kung University, Tainan, Taiwan. Electronic address: leochen@nhri.org.tw. ·Lancet · Pubmed #26615328.

ABSTRACT: BACKGROUND: Nanoliposomal irinotecan showed activity in a phase 2 study in patients with metastatic pancreatic ductal adenocarcinoma previously treated with gemcitabine-based therapies. We assessed the effect of nanoliposomal irinotecan alone or combined with fluorouracil and folinic acid in a phase 3 trial in this population. METHODS: We did a global, phase 3, randomised, open-label trial at 76 sites in 14 countries. Eligible patients with metastatic pancreatic ductal adenocarcinoma previously treated with gemcitabine-based therapy were randomly assigned (1:1) using an interactive web response system at a central location to receive either nanoliposomal irinotecan monotherapy (120 mg/m(2) every 3 weeks, equivalent to 100 mg/m(2) of irinotecan base) or fluorouracil and folinic acid. A third arm consisting of nanoliposomal irinotecan (80 mg/m(2), equivalent to 70 mg/m(2) of irinotecan base) with fluorouracil and folinic acid every 2 weeks was added later (1:1:1), in a protocol amendment. Randomisation was stratified by baseline albumin, Karnofsky performance status, and ethnic origin. Treatment was continued until disease progression or intolerable toxic effects. The primary endpoint was overall survival, assessed in the intention-to-treat population. The primary analysis was planned after 305 events. Safety was assessed in all patients who had received study drug. This trial is registered at ClinicalTrials.gov, number NCT01494506. FINDINGS: Between Jan 11, 2012, and Sept 11, 2013, 417 patients were randomly assigned either nanoliposomal irinotecan plus fluorouracil and folinic acid (n=117), nanoliposomal irinotecan monotherapy (n=151), or fluorouracil and folinic acid (n=149). After 313 events, median overall survival in patients assigned nanoliposomal irinotecan plus fluorouracil and folinic acid was 6.1 months (95% CI 4.8-8.9) vs 4.2 months (3.3-5.3) with fluorouracil and folinic acid (hazard ratio 0.67, 95% CI 0.49-0.92; p=0.012). Median overall survival did not differ between patients assigned nanoliposomal irinotecan monotherapy and those allocated fluorouracil and folinic acid (4.9 months [4.2-5.6] vs 4.2 months [3.6-4.9]; 0.99, 0.77-1.28; p=0.94). The grade 3 or 4 adverse events that occurred most frequently in the 117 patients assigned nanoliposomal irinotecan plus fluorouracil and folinic acid were neutropenia (32 [27%]), diarrhoea (15 [13%]), vomiting (13 [11%]), and fatigue (16 [14%]). INTERPRETATION: Nanoliposomal irinotecan in combination with fluorouracil and folinic acid extends survival with a manageable safety profile in patients with metastatic pancreatic ductal adenocarcinoma who previously received gemcitabine-based therapy. This agent represents a new treatment option for this population. FUNDING: Merrimack Pharmaceuticals.

16 Clinical Trial Phase II trial of gemcitabine and tanespimycin (17AAG) in metastatic pancreatic cancer: a Mayo Clinic Phase II Consortium study. 2015

Pedersen, Katrina S / Kim, George P / Foster, Nathan R / Wang-Gillam, Andrea / Erlichman, Charles / McWilliams, Robert R. ·Division of Medical Oncology, Mayo Clinic, Rochester, MN, USA, pedersen.katrina@mayo.edu. ·Invest New Drugs · Pubmed #25952464.

ABSTRACT: OBJECTIVES: Heat Shock Protein 90 (HSP90) is a molecular chaperone that stabilizes many oncogenic proteins. HSP90 inhibitors may sensitize tumors to cytotoxic agents by causing client protein degradation. Gemcitabine, which has modest activity in pancreas cancer, activates Chk1, a client protein of HSP90. This phase II trial was designed to determine whether 17AAG could enhance the clinical activity of gemcitabine through degradation of Chk1 in patients with stage IV pancreatic cancer. METHODS: A multicenter, prospective study combining gemcitabine and 17AAG enrolled patients with stage IV pancreatic adenocarcinoma, adequate liver and kidney function, ECOG performance status 0-2, and no prior chemotherapy for metastatic disease. The primary goal was to achieve a 60 % overall survival at 6 months. Sixty-six patients were planned for accrual, with an interim analysis after 25 patients enrolled. RESULTS: After a futility analysis to achieve the endpoint, accrual was halted with 21 patients enrolled. No complete or partial responses were seen. Forty percent of patients were alive at 6 months. Median overall survival was 5.4 months. Tolerability was moderate, with 65 % of patients having ≥ grade 3 adverse events (AE), and 15 % having grade 4 events. CONCLUSIONS: The lack of clinical activity suggests that targeting Chk1 by inhibiting HSP90 is not important in pancreatic cancer sensitivity to gemcitabine alone. Further studies of HSP90 targeted agents with gemcitabine alone are not warranted.

17 Clinical Trial A phase II study of adjuvant gemcitabine plus docetaxel followed by concurrent chemoradation in resected pancreaticobiliary carcinoma. 2015

Cho, May / Wang-Gillam, Andrea / Myerson, Robert / Gao, Feng / Strasberg, Steven / Picus, Joel / Sorscher, Steven / Fournier, Chloe / Nagaraj, Gayathri / Parikh, Parag / Suresh, Rama / Linehan, David / Tan, Benjamin R. ·Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA. · Department of Radiation Oncology, Washington University School of Medicine, St. Louis, MO, USA. · Division of Biostatistics, Washington University School of Medicine, St. Louis, MO, USA. · Department of Surgery, Washington University School of Medicine, St. Louis, MO, USA. · Division of Medical Oncology and Hematology, Loma Linda University, Loma Linda, CA, USA. ·HPB (Oxford) · Pubmed #25800066.

ABSTRACT: OBJECTIVES: Adjuvant gemcitabine with or without chemoradiation is a standard therapeutic option for patients with resected pancreatic cancer. The feasibility and toxicity of gemcitabine with docetaxel before and after 5-fluorouracil (5FU)-based chemoradiation in the adjuvant pancreatic and biliary cancer setting were investigated. METHODS: After a curative-intent resection, eligible patients with pancreaticobiliary cancers were treated with two cycles of gemcitabine and docetaxel followed by 5FU-based chemoradiation. Four weeks after completing chemoradiation, two cycles of gemcitabine and docetaxel were administered. The primary endpoint was the incidence of severe toxicities. Secondary endpoints included disease-free survival (DFS) and overall survival (OS). RESULTS: Fifty patients with pancreaticobiliary cancers were enrolled. Twenty-nine patients had pancreatic cancer whereas 21 patients had biliary tract or ampullary cancers. There was one death as a result of pneumonia, and 15% of patients experienced grade 3 or greater non-haematological toxicities. The median DFS and OS for patients with pancreatic cancer were 9.6 and 17 months, respectively, and for those with resected biliary tract cancer were 12 and 23 months, respectively. CONCLUSIONS: This combination of gemcitabine and docetaxel with chemoradiation is feasible and tolerable in the adjuvant setting. Future studies utilizing a different gemcitabine/taxane combination and schedule may be appropriate in the adjuvant treatment of both pancreatic cancer and biliary tumours.

18 Clinical Trial Safety and survival with GVAX pancreas prime and Listeria Monocytogenes-expressing mesothelin (CRS-207) boost vaccines for metastatic pancreatic cancer. 2015

Le, Dung T / Wang-Gillam, Andrea / Picozzi, Vincent / Greten, Tim F / Crocenzi, Todd / Springett, Gregory / Morse, Michael / Zeh, Herbert / Cohen, Deirdre / Fine, Robert L / Onners, Beth / Uram, Jennifer N / Laheru, Daniel A / Lutz, Eric R / Solt, Sara / Murphy, Aimee Luck / Skoble, Justin / Lemmens, Ed / Grous, John / Dubensky, Thomas / Brockstedt, Dirk G / Jaffee, Elizabeth M. ·Dung T. Le, Beth Onners, Jennifer N. Uram, Daniel A. Laheru, Eric R. Lutz, Sara Solt, and Elizabeth M. Jaffee, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore · Tim F. Greten, National Cancer Institute, Bethesda, MD · Andrea Wang-Gillam, Siteman Cancer Center, Washington University, St Louis, MO · Vincent Picozzi, Virginia Mason Medical Center, Seattle, WA · Todd Crocenzi, Providence Portland Medical Center, Portland, OR · Gregory Springett, Moffitt Cancer Center, Tampa, FL · Michael Morse, Duke University Medical Center, Durham, NC · Herbert Zeh, University of Pittsburgh, Pittsburgh, PA · Deirdre Cohen, New York University Langone Medical Center · Robert L. Fine, Columbia University Medical Center, New York, NY · and Aimee Luck Murphy, Justin Skoble, Ed Lemmens, John Grous, Thomas Dubensky Jr, and Dirk G. Brockstedt, Aduro BioTech, Berkeley, CA. ·J Clin Oncol · Pubmed #25584002.

ABSTRACT: PURPOSE: GVAX pancreas, granulocyte-macrophage colony-stimulating factor-secreting allogeneic pancreatic tumor cells, induces T-cell immunity to cancer antigens, including mesothelin. GVAX is administered with low-dose cyclophosphamide (Cy) to inhibit regulatory T cells. CRS-207, live-attenuated Listeria monocytogenes-expressing mesothelin, induces innate and adaptive immunity. On the basis of preclinical synergy, we tested prime/boost vaccination with GVAX and CRS-207 in pancreatic adenocarcinoma. PATIENTS AND METHODS: Previously treated patients with metastatic pancreatic adenocarcinoma were randomly assigned at a ratio of 2:1 to two doses of Cy/GVAX followed by four doses of CRS-207 (arm A) or six doses of Cy/GVAX (arm B) every 3 weeks. Stable patients were offered additional courses. The primary end point was overall survival (OS) between arms. Secondary end points were safety and clinical response. RESULTS: A total of 90 patients were treated (arm A, n = 61; arm B, n = 29); 97% had received prior chemotherapy; 51% had received ≥ two regimens for metastatic disease. Mean number of doses (± standard deviation) administered in arms A and B were 5.5 ± 4.5 and 3.7 ± 2.2, respectively. The most frequent grade 3 to 4 related toxicities were transient fevers, lymphopenia, elevated liver enzymes, and fatigue. OS was 6.1 months in arm A versus 3.9 months in arm B (hazard ratio [HR], 0.59; P = .02). In a prespecified per-protocol analysis of patients who received at least three doses (two doses of Cy/GVAX plus one of CRS-207 or three of Cy/GVAX), OS was 9.7 versus 4.6 months (arm A v B; HR, 0.53; P = .02). Enhanced mesothelin-specific CD8 T-cell responses were associated with longer OS, regardless of treatment arm. CONCLUSION: Heterologous prime/boost with Cy/GVAX and CRS-207 extended survival for patients with pancreatic cancer, with minimal toxicity.

19 Clinical Trial A phase I study of IMP321 and gemcitabine as the front-line therapy in patients with advanced pancreatic adenocarcinoma. 2013

Wang-Gillam, Andrea / Plambeck-Suess, Stacey / Goedegebuure, Peter / Simon, Peter O / Mitchem, Jonathan B / Hornick, John R / Sorscher, Steven / Picus, Joel / Suresh, Rama / Lockhart, Albert C / Tan, Benjamin / Hawkins, Williams G. ·Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA. ·Invest New Drugs · Pubmed #22864469.

ABSTRACT: PURPOSE: This phase I study was conducted to determine the safety profile and maximum tolerated dose (MTD) of IMP321, a soluble lymphocyte activation gene-3 (LAG-3) Ig fusion protein and MHC Class II agonist, combined with gemcitabine in patients with advanced pancreatic adenocarcinoma. PATIENTS AND METHODS: Patients with advanced pancreatic adenocarcinoma were treated with gemcitabine (1,000 mg/m(2))(level 1), gemcitabine (1,000 mg/m(2)) plus IMP 321 at 0.5 mg (level 2) and 2.0 mg (level 3), respectively. Safety, toxicity, and immunological markers at baseline and post treatment were assessed. RESULTS: A total of 18 patients were enrolled to the study, and 17 were evaluable for toxicity. None of the 6 patients who received 0.5 mg IMP321 experienced IMP321-related adverse events. Of the 5 patients who received IMP321 at the 2 mg dose level, 1 experienced rash, 1 reported hot flashes and 2 had mild pain at the injection sites. No severe adverse events previously attributed to IMP321 were observed. No significant differences were observed when comparing pre- and post-treatment levels of monocytes (CD11b+CD14+), conventional dendritic cells (CD11c+) or T cell subsets (CD4, CD8). CONCLUSIONS: IMP321 in combination with gemcitabine is a well-tolerated regimen. IMP321 did not result in any severe adverse events. No incremental activity observed for the additional IMP 321 to gemcitabine at the dose levels evaluated, likely due to sub-optimal dosing. Immunological markers suggested that higher dose levels of IMP321 are needed for future clinical studies.

20 Clinical Trial Multi-institutional experience with FOLFIRINOX in pancreatic adenocarcinoma. 2012

Peddi, Parvin F / Lubner, Sam / McWilliams, Robert / Tan, Benjamin R / Picus, Joel / Sorscher, Steven M / Suresh, Rama / Lockhart, A Craig / Wang, Jian / Menias, Christine / Gao, Feng / Linehan, David / Wang-Gillam, Andrea. ·Division of Medical Oncology, Department of Medicine, Washington University School of Medicine, Saint Louis, MO 63110, USA. ·JOP · Pubmed #22964956.

ABSTRACT: CONTEXT: Combination chemotherapy with FOLFIRINOX (oxaliplatin, irinotecan, fluorouracil, and leucovorin) was shown to be effective in a large phase III trial. OBJECTIVE: The purpose of this study was to examine the tolerance and effectiveness of FOLFIRINOX as practiced outside of the confines of a clinical trial and to document any dose modifications used by practicing oncologists. METHODS: Data on patients with all stages of pancreatic adenocarcinoma treated with FOLFIRINOX at three institutions was analyzed for efficacy, tolerance, and use of any dose modifications. RESULTS: Total of 61 patients was included in this review. Median age was 58 years (range: 37 to 72 years), 33 were male (54.1%) and majority had ECOG performance of 0 or 1 (86.9%, 53 patients). Thirty-eight (62.3%) had metastatic disease, while 23 (37.7%) were treated for locally advanced or borderline resectable disease. Patients were treated with a median number of four cycles of FOLFIRINOX, with dose modifications in 58.3% (176/302) of all cycles. Ten patients had stable disease (16.4%), four had a partial response (6.6%) while eight had progressive disease (13.1%) on best imaging following therapy. Median progression-free survival and overall survival were 7.5 months and 13.5 months, respectively. The most common grade 3-4 adverse event was neutropenia at 19.7% (12 cases), with 4.9% (3 cases) rate of febrile neutropenia. Twenty-one patients (34.4%) were hospitalized as a result of therapy but there were no therapy-related deaths. Twenty-three (37.7%) had therapy eventually discontinued as a result of adverse events. CONCLUSION: Despite substantial rates of adverse events and use of dose modifications, FOLFIRINOX was found to be clinically effective in both metastatic and non-metastatic patients. Regimen toxicity did not detract from overall response and survival.

21 Article Phase Ib/II study combining tosedostat with capecitabine in patients with advanced pancreatic adenocarcinoma. 2020

Grierson, Patrick / Teague, Andrea / Suresh, Rama / Lim, Kian-Huat / Amin, Manik / Pedersen, Katrina / Tan, Benjamin / Huffman, Jesse / Boice, Nick / Du, Lingling / Liu, Jingxia / Lockhart, A Craig / Wang-Gillam, Andrea. ·Department of Internal Medicine, Division of Medical Oncology, Washington University in St. Louis, St. Louis, MO, USA. · New Mexico Cancer Care Associates, Santa Fe, NM, USA. · Ochsner Health System, New Orleans, LA, USA. · Department of Surgery, Division of Public Health Sciences, Section of Oncologic Biostatistics, Washington University in St. Louis, St. Louis, MO, USA. · University of Miami, Miller School of Medicine, Sylvester Comprehensive Cancer Center, Miami, FL, USA. ·J Gastrointest Oncol · Pubmed #32175106.

ABSTRACT: Background: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with limited therapeutic options. We evaluated the safety and efficacy of the aminopeptidase inhibitor tosedostat with capecitabine in advanced PDAC. Methods: We conducted a phase Ib/II trial of tosedostat with capecitabine as second-line therapy for advanced PDAC. Planned enrollment was 36 patients. Eligible patients were treated with capecitabine 1,000 mg/m Results: Sixteen patients were enrolled. Tosedostat 120 mg oral twice daily with capecitabine 1,000 mg/m Conclusions: Tosedostat with capecitabine displayed tolerable toxicity, and prolonged disease control in a subset of patients. These data encourage further exploration of aminopeptidase inhibitors in pancreatic cancer.

22 Article A randomized phase II trial of nab-paclitaxel and gemcitabine with tarextumab or placebo in patients with untreated metastatic pancreatic cancer. 2019

Hu, Zishuo Ian / Bendell, Johanna C / Bullock, Andrea / LoConte, Noelle K / Hatoum, Hassan / Ritch, Paul / Hool, Hugo / Leach, Joseph W / Sanchez, James / Sohal, Davendra P S / Strickler, John / Patel, Ravindranath / Wang-Gillam, Andrea / Firdaus, Irfan / Yu, Kenneth H / Kapoun, Ann M / Holmgren, Eric / Zhou, Lei / Dupont, Jakob / Picozzi, Vincent / Sahai, Vaibhav / O'Reilly, Eileen M. ·Memorial Sloan Kettering Cancer Center, New York, New York. · Sarah Cannon Research Institute/Tennessee Oncology, Nashville, Tennessee. · Beth Israel Deaconess Medical Center, Boston, Massachusetts. · University of Wisconsin, Cancer Center, Madison, Wisconsin. · University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma. · Froedtert Hospital and Medical College of Wisconsin, Milwaukee, Wisconsin. · Torrance Memorial Physician Network, Redondo Beach, California. · Virginia Piper Cancer Institute, Minneapolis, Minnesota. · Comprehensive Cancer Centers of Nevada, Henderson, Nevada. · Cleveland Clinic, Cleveland, Ohio. · Duke University, Durham, North Carolina. · Comprehensive Blood and Cancer Center, Bakersfield, California. · Washington University School of Medicine, Saint Louis, Missouri. · Oncology Hematology Cancer, Inc., Cincinnati, Ohio. · David M. Rubenstein Center for Pancreatic Cancer Research, New York, New York. · Department of Medicine, Weill Cornell Medical College, New York, New York. · Oncomed Pharmaceuticals Inc, Redwood City, California. · Virginia Mason Medical Center, Seattle, Washington. · University of Michigan, Ann Arbor, Michigan. ·Cancer Med · Pubmed #31347292.

ABSTRACT: PURPOSE: Notch signaling dysregulation is implicated in the development of pancreatic adenocarcinoma (PDAC). Tarextumab is a fully human IgG2 antibody that inhibits Notch2/3 receptors. PATIENTS AND METHODS: Aphase 2, randomized, placebo-controlled, multicenter trial evaluated the activity of tarextumab in combination with nab-paclitaxel and gemcitabine in patients with metastatic PDAC. Patients were stratified based on ECOG performance score and Ca 19-9 level and randomized 1:1 to nab-paclitaxel, gemcitabine with either tarextumab or placebo. Based on preclinical and phase Ib results suggesting a positive correlation between Notch3 gene expression and tarextumab anti-tumor activity, patients were also divided into subgroups of low, intermediate, and high Notch3 gene expression. Primary endpoint was overall survival (OS) in all and in patients with the three Notch3 gene expression subgroups (≥25th, ≥50% and ≥75% percentiles); secondary end points included progression-free survival (PFS), 12-month OS, overall response rate (ORR), and safety and biomarker investigation. RESULTS: Median OS was 6.4 months in the tarextumab group vs 7.9 months in the placebo group (HR = 1.34 [95% CI = 0.95, 1.89], P = .0985). No difference observed in OS in the Notch3 gene expression subgroups. PFS in the tarextumab-treated group (3.7 months) was significantly shorter compared with the placebo group (5.5 months) (hazard ratio was 1.43 [95% CI = 1.01, 2.01]; P = .04). Grade 3 diarrhea and thrombocytopenia were more common in the tarextumab group. CONCLUSIONS: The addition of tarextumab to nab-paclitaxel and gemcitabine did not improve OS, PFS, or ORR in first-line metastatic PDAC, and PFS was specifically statistically worse in the tarextumab-treated patients. CLINICAL TRIAL REGISTRY NO: NCT01647828.

23 Article Results from a Phase IIb, Randomized, Multicenter Study of GVAX Pancreas and CRS-207 Compared with Chemotherapy in Adults with Previously Treated Metastatic Pancreatic Adenocarcinoma (ECLIPSE Study). 2019

Le, Dung T / Picozzi, Vincent J / Ko, Andrew H / Wainberg, Zev A / Kindler, Hedy / Wang-Gillam, Andrea / Oberstein, Paul / Morse, Michael A / Zeh, Herbert J / Weekes, Colin / Reid, Tony / Borazanci, Erkut / Crocenzi, Todd / LoConte, Noelle K / Musher, Benjamin / Laheru, Dan / Murphy, Aimee / Whiting, Chan / Nair, Nitya / Enstrom, Amanda / Ferber, Sandy / Brockstedt, Dirk G / Jaffee, Elizabeth M. ·The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland. dle@jhmi.edu. · Virginia Mason Medical Center, Seattle, Washington. · University of California San Francisco, San Francisco, California. · University of California Los Angeles, Los Angeles, California. · University of Chicago Medical Center, Chicago, Illinois. · Washington University School of Medicine in St. Louis, St. Louis, Missouri. · Columbia University Medical Center, New York, New York. · Duke University Medical Center, Durham, North Carolina. · University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania. · University of Colorado Cancer Center, Aurora, Colorado. · University of San Diego Moores Cancer Center, La Jolla, California. · HonorHealth, Tgen, Scottsdale, Arizona. · Providence Cancer Center, Portland, Oregon. · University of Wisconsin Carbone Cancer Center, Madison, Wisconsin. · Baylor College of Medicine, Houston, Texas. · The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland. · Aduro Biotech, Berkeley, California. · Array Biostatistics, LLC, Chicago, Illinois. ·Clin Cancer Res · Pubmed #31126960.

ABSTRACT: PURPOSE: Limited options exist for patients with advanced pancreatic cancer progressing after 1 or more lines of therapy. A phase II study in patients with previously treated metastatic pancreatic cancer showed that combining GVAX pancreas (granulocyte-macrophage colony-stimulating factor-secreting allogeneic pancreatic tumor cells) with cyclophosphamide (Cy) and CRS-207 (live, attenuated PATIENTS AND METHODS: Patients with previously treated metastatic pancreatic adenocarcinoma were randomized 1:1:1 to receive Cy/GVAX + CRS-207 (arm A), CRS-207 (arm B), or physician's choice of single-agent chemotherapy (arm C). The primary cohort included patients who had failed ≥2 prior lines of therapy, including gemcitabine. The primary objective compared OS between arms A and C in the primary cohort. The second-line cohort included patients who had received 1 prior line of therapy. Additional objectives included OS between all treatment arms, safety, and tumor responses. RESULTS: The study did not meet its primary efficacy endpoint. At the final study analysis, median OS [95% confidence interval (CI)] in the primary cohort ( CONCLUSIONS: The combination of Cy/GVAX + CRS-207 did not improve survival over chemotherapy. (ClinicalTrials.gov ID: NCT02004262)

24 Article Liposomal irinotecan and 5-fluorouracil/leucovorin in older patients with metastatic pancreatic cancer - A subgroup analysis of the pivotal NAPOLI-1 trial. 2019

Macarulla, Teresa / Blanc, Jean-Frédéric / Wang-Gillam, Andrea / Chen, Li-Tzong / Siveke, Jens T / Mirakhur, Beloo / Chen, Jie / de Jong, Floris A. ·Vall d'Hebron University Hospital (HUVH), Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain. Electronic address: tmacarulla@vhebron.net. · Pôle ADEN, Hôpital Haut-Lévêque, CHU Bordeaux, Bordeaux, France. · Division of Oncology, Washington University in St. Louis, MO, USA. · National Institute of Cancer Research, National Health Research Institutes, National Cheng Kung University, Tainan, Taiwan; Department of Internal Medicine, National Cheng Kung University, Tainan, Taiwan. · Division of Solid Tumor Translational Oncology, West German Cancer Center, University Hospital Essen, Essen, Germany; Cancer Consortium (DKTK, partner site Essen), German Cancer Research Center, DKFZ, Heidelberg, Germany. · Ipsen Biopharmaceuticals, Inc., Cambridge, MA, United States. · Shire plc, Cambridge, MA, United States. · Global Medical Affairs, Servier, Zurich, Switzerland. ·J Geriatr Oncol · Pubmed #30842038.

ABSTRACT: OBJECTIVES: Pancreatic cancer is a highly lethal disease predominantly affecting older patients. Characterization of outcomes in these patients may help optimise treatment decisions. The global, phase 3 NAPOLI-1 trial (NCT01494506) demonstrated an overall survival (OS) benefit with liposomal irinotecan and 5-flurouracil/leucovorin (nal-IRI + 5-FU/LV) versus 5-FU/LV. This subgroup analysis explored impact of age on outcomes in NAPOLI-1 patients, and nal-IRI + 5-FU/LV efficacy and safety in older patients. MATERIALS AND METHODS: This exploratory, post-hoc analysis of the NAPOLI-1 trial included patients aged ≥eighteen years (no upper limit) with metastatic pancreatic adenocarcinoma that had progressed on gemcitabine-based therapy. Patients were stratified by age (cut-offs at 65, 70, and 75 years); OS and progression-free survival (PFS) were estimated by Kaplan-Meier analysis. RESULTS: Of 417 randomized patients, 192 (46%), 110 (26%) and 43 (10%) were aged ≥65, ≥70 and ≥ 75 years, respectively. Mortality risk and risk of disease progression were similar in older and younger patients independent of treatment (HRs for median [m]OS/mPFS comparisons were 0.88/0.95 [<65 versus ≥65 years], 0.89/0.88 [<70 versus ≥70 years] and 1.04/0.98 [<75 versus ≥75 years]; P > .25). Reduced mortality/morbidity risk with nal-IRI + 5-FU/LV in older subgroups was in line with the wider population. No additional toxicities with nal-IRI + 5-FU/LV were observed in older patients: 86% of patients ≥75 years versus 69% <75 years required a dose delay or reduction due to toxicities (43% versus 32% dose reductions). DISCUSSION: Results suggest that older patients with metastatic pancreatic adenocarcinoma that progressed on prior gemcitabine-based treatment can benefit from second-line therapy, supporting nal-IRI + 5-FU/LV treatment in older patients.

25 Article Quality of life in metastatic pancreatic cancer patients receiving liposomal irinotecan plus 5-fluorouracil and leucovorin. 2019

Hubner, Richard A / Cubillo, Antonio / Blanc, Jean-Frédéric / Melisi, Davide / Von Hoff, Daniel D / Wang-Gillam, Andrea / Chen, Li-Tzong / Becker, Claus / Mamlouk, Khalid / Belanger, Bruce / Yang, Yoojung / de Jong, Floris A / Siveke, Jens T. ·Department of Medical Oncology, The Christie NHS Foundation Trust, 550 Wilmslow Rd, Manchester, M20 4BX, UK. Electronic address: Richard.Hubner@christie.nhs.uk. · Centro Integral Oncológico Clara Campal (CIOCC), HM Universitario Madrid Sanchinarro, C/ Oña, 10, 28050, Madrid, Spain; Departamento de Ciencias Médicas Clínicas, Universidad CEU San Pablo, C/ Oña, 10, 28050, Madrid, Spain. · Hepato-Gastroentertology and Digestive Oncology Unit, Hôpital Haut-Lévêque, CHU Bordeaux, Av. Magellan, 33600, Pessac, France. · Digestive Molecular Clinical Oncology Unit, University of Verona, Piazzale L.A. Scuro, 10, 37134, Verona, Italy. · Translational Genomics Research Institute and Honor Health, 10510 N 92nd St, #200, Scottsdale, AZ, 85258, USA. · Washington University in St. Louis, 1 Brookings Dr, St. Louis, MO, 63130, USA. · National Institute of Cancer Research, National Health Research Institutes (NHRI), 367 Sheng-Li Road, Tainan, 704, Taiwan. · Merrimack Pharmaceuticals, Inc., 1 Kendall Square, B7201, Cambridge, MA, 02139, USA. · Ipsen Biopharmaceuticals, Inc., 650 E. Kendall Street, Cambridge, MA, 02142, USA. · Shire, Zählerweg 10, 6300, Zug, Switzerland. · Division of Solid Tumor Translational Oncology, West German Cancer Center, University Hospital Essen, Hufelandstrasse 55, 45147, Essen, Germany; German Cancer Consortium (DKTK, Partner Site Essen) and German Cancer Research Center, DKFZ, Im Neuenheimer Feld 280, 69120, Heidelberg, Germany. ·Eur J Cancer · Pubmed #30458340.

ABSTRACT: BACKGROUND: The NAPOLI-1 study (NCT01494506) reported that liposomal irinotecan plus 5-fluorouracil and leucovorin (nal-IRI+5-FU/LV) improved overall survival vs 5-FU/LV with manageable toxicity in patients with metastatic pancreatic adenocarcinoma previously treated with gemcitabine-based therapy. Yet, clinicians need treatment strategies that also maintain the patient's health-related quality of life (HRQOL). Here, we report the HRQOL data. METHODS: Patients completed the European Organisation for Research and Treatment of Cancer QOL core questionnaire C30 (EORTC QLQ-C30) at baseline, every 6 weeks, and at 30 days after discontinuation of study treatment. Patient-reported outcomes (PROs) were scored according to EORTC guidelines. nal-IRI+5-FU/LV HRQOL was compared with 5-FU/LV. The PRO population comprised intent-to-treat patients who completed baseline and at least one subsequent assessment on the EORTC QLQ-C30. Data were also analysed for missingness. RESULTS: Of 236 patients in the intent-to-treat population, 128 (54.2%) comprised the PRO population (71 in the nal-IRI+5-FU/LV arm; 57 the in 5-FU/LV arm). Of the remaining 108 patients (45.8%) not included in the PRO population, most progressed rapidly, making participation difficult. Median change from baseline was ≤10 points at weeks 6 and 12 in global health status or functional and symptom scale scores, except for fatigue, which deteriorated by 11.1 points with nal-IRI+5-FU/LV but did not change vs 5-FU/LV. The proportion of patients whose HRQOL improved or deteriorated was not significantly different between the arms. CONCLUSION: In the NAPOLI-1 study, HRQOL was maintained with nal-IRI+5-FU/LV in patients with metastatic pancreatic adenocarcinoma previously treated with a gemcitabine-based regimen, while survival was significantly extended.

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