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Acknowledgment of Commercial Support

This activity is supported by educational grants from Celgene Corporation and Ipsen Biopharmaceuticals, Inc.

Accreditation/Credit Designation

Physicians' Education Resource®, LLC, is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.

Physicians' Education Resource®, LLC, designates this enduring material for a maximum of 1.5 AMA PRA Category 1 Credits. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Medical Crossfire®: Navigating Treatment Decisions in Pancreatic Cancer: Key Questions


Release Date: June 29, 2018
Expiration Date: June 29, 2019
Media: Internet - based
 

Activity Overview

Despite treatment advances, pancreatic cancer is associated with a relatively poor outcome for most patients. A high level of integrated multidisciplinary cooperation can positively impact patient outcomes across the disease spectrum, from diagnosis to treatment and end-of-life care. In this Medical Crossfire® activity, moderated by Eileen M. O'Reilly, MD, you will engage with renowned surgical, radiation, and medical experts, Michael A. Choti, MD, Christopher Crane, MD, and George P. Kim, MD; gain insight into recommended treatment options and sequencing; consider the neoadjuvant, adjuvant, and surgical decision making necessary to manage patients with advanced pancreatic cancer; and compare the novel formulations of therapeutic options to inform treatment decisions.

For busy oncologists engaged in the daily management of complex patients with advanced pancreatic malignancies, this activity provides you with a multidisciplinary perspective to incorporate into the patient care setting.

Below are some clinical pearls and highlights from the activity:

  • Recent treatment advances have led to improvements in overall survival for some patients with metastatic pancreatic ductal adenocarcinoma (PDAC), but significant effort is still needed to further develop screening and treatment modalities to improve long-term patient outcomes. 
  • Novel drug delivery formulations incorporating nanovectors, such as nab-paclitaxel and nanoliposomal irinotecan, play an important role in the treatment of advanced pancreatic adenocarcinoma. Enhanced understanding of the biology of PDAC will potentially lead to new treatment options directed against both the cancer cells and the surrounding microenvironment.
  • Close monitoring and management of toxicities is critical for patients with advanced PDAC because they may be at increased risk due to compromised performance status prior to treatment initiation.

Acknowledgment of Commercial Support

This activity is supported by educational grants from Celgene Corporation and Ipsen Biopharmaceuticals, Inc.

Instructions for This Activity and Receiving Credit

  • You will need to login to participate in the activity.
  • Each presentation may contain an interactive question(s). You may move forward through the presentation; however, you may not go back to change answers or review videos/content until you finish the presentation.
  • At the end of the activity, “educational content/video files” will be available for your reference.
  • In order to receive a CME certificate, participants must complete the activity.
  • Complete the posttest and pass with a score of 70% or higher, complete the evaluation and then click on request for credit. Participants may immediately download a CME certificate upon completion of these steps.

Target Audience

This educational activity is directed toward medical oncologists, gastroenterologists, nutritionists, nurse practitioners, physician assistants, nurses, and other healthcare professionals interested in the treatment of pancreatic cancer. This activity will provide education to a broad multidisciplinary team who are invited to participate.

Learning Objectives

At the conclusion of this activity, participants should be better prepared to:

  1. Identify pharmacodynamic and pharmacokinetic properties of treatments for pancreatic cancer
  2. Evaluate clinical trial data regarding the efficacy of albumin-bound paclitaxel, liposomal irinotecan, and FOLFIRINOX in metastatic pancreatic cancer
  3. Place recent clinical trial findings in the context of evolving treatment paradigms in the field of advanced pancreatic cancer management
  4. Explain adverse events and approaches for the management of treatment-related toxicities across multiple lines of therapy in patients with pancreatic cancer
Moderator

Eileen M. O'Reilly, MD
Associate Director
David M. Rubenstein Center for Pancreatic Cancer
Professor of Medicine, Weill Cornell Medical College
Attending Physician, Member
Memorial Sloan Kettering Cancer Center
New York, NY
 

DisclosuresGrant/Research Support: Agios, Array, AstraZeneca, Bayer, BMS, Casi, Celgene, Exelixis, Genentech, Incyte, Lilly, MabVax, MedImmune, Momenta, Novartis, OncoMed Pharmaceuticals, Roche; Consultant: Agios, Amgen, Antengene, Aptus, Aslan, Astellas, AstraZeneca, Bayer, BMS, Boston Scientific, CARsgen, Celgene, Casi, CytomX, Daiichi, Debio, Delcath, Eisai, Exelixis, Gilead, Halozyme, Inovio, Ipsen, Merck, Onxeo, PCI Biotech, Roche, Sanofi, Servier, Silenseed, Sillajen, Sirtex, Vicus, Yakult

Faculty

Michael A. Choti, MD
Chief of Surgery
Banner MD Anderson Cancer Center
Phoenix, AZ
 
 

Disclosures: Dr. Michael Choti has no relevant financial relationships with commercial interests to disclose.

Christopher Crane, MD
Radiation Oncologist
Vice Chair, Department of Radiation Oncology
Attending Physician, Member
Memorial Sloan Kettering Cancer Center
New York, NY

Disclosure: Consultant: Celgene

George P. Kim, MD
Member, US Intergroup NCI Pancreas Cancer Task Force
Jacksonville, FL
 
 
 

DisclosuresConsultant: Celgene, Ipsen; Speaker’s Bureau: Celgene, Ipsen

The staff of Physicians' Education Resource®, LLC, (PER®) have no relevant financial relationships with commercial interests to disclose.

Disclosure Policy and Resolution of Conflicts of Interest (COI)

As a sponsor accredited by the ACCME, it is the policy of PER® to ensure fair balance, independence, objectivity, and scientific rigor in all of its CME activities. In compliance with ACCME guidelines, PER® requires everyone who is in a position to control the content of a CME activity to disclose all relevant financial relationships with commercial interests. The ACCME defines “relevant financial relationships” as financial relationships in any amount occurring within the past 12 months that creates a COI.

Additionally, PER® is required by ACCME to resolve all COI. PER® has identified and resolved all COI prior to the start of this activity by using a multistep process.

Off-Label Disclosure and Disclaimer

This CME activity may or may not discuss investigational, unapproved, or off-label use of drugs. Participants are advised to consult prescribing information for any products discussed. The information provided in this CME activity is for continuing medical and nursing education purposes only, and is not meant to substitute for the independent clinical judgment of a physician relative to diagnostic, treatment, or management options for a specific patient’s medical condition. The opinions expressed in the content are solely those of the individual faculty members and do not reflect those of PER or any of the companies that provided commercial support for this activity.

PER Pulse Recap™

PER Pulse Recap (1 of 3)

Join Moderator Eileen M. O'Reilly, MD, and renowned surgical, radiation, and medical experts, Michael A. Choti, MD, Christopher Crane, MD, and George P. Kim, MD, in the online continuing medical education (CME) activity, Medical Crossfire®: Navigating Treatment Decisions in Pancreatic Cancer: Key Questions. You will gain insight into recommended treatment options and sequencing; consider the neoadjuvant, adjuvant, and surgical decision making necessary to manage patients with advanced pancreatic cancer; and compare the novel formulations of therapeutic options to inform treatment decisions.
 
This first of 3 PER Pulse™ Recaps will focus on patient evaluation and staging in pancreatic cancer.
 
Pancreatic cancer is currently the fourth most common cause of cancer-related death among Americans; pancreatic ductal adenocarcinoma (PDAC) is projected to become the second leading cause of cancer-related death by 2020.1,2 Approximately 80% of cases of pancreatic cancer are diagnosed at an advanced stage with locally advanced or metastatic disease. Most patients die within 2 years of diagnosis, and the 5-year survival rate is less than 5%.3
 
Dr. Choti discusses surgical interventions in pancreatic cancer, with curative or palliative intent, based on patient characteristics and stage at diagnosis.

“The key question in pancreatic cancer is, ‘Is it surgically operable?’ That’s the mainstay of potentially curative options, and unfortunately most patients are not candidates for surgery.”
 — Michael A. Choti, MD

Most patients are managed with systemic treatments. Dr. Crane highlights the importance of biomarkers, including carbohydrate antigen 19-9 (CA 19-9), to evaluate treatment response in patients with PDAC.

“I always evaluate the CA 19-9, not only what it was at diagnosis, but what it has done on chemotherapy. Patients are on systemic therapy, and I think it’s important to see if there is a response to treatment.”
 — Christopher Crane, MD

References
  1. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) Pancreatic Adenocarcinoma. Version 1.2018. www.nccn.org.
  2. Torres C, Grippo PJ. Pancreatic cancer subtypes: a roadmap for precision medicine. Ann Med. 2018;50:277-287. doi: 10.1080/07853890.2018.1453168.
  3. Ansari D, Gustafsson A, Andersson R. Update on the management of pancreatic cancer: surgery is not enough. World J Gastroenterol. 2015;21:3157-3165. doi: 10.3748/wjg.v21.i11.3157.

PER Pulse Recap (2 of 3)

This second of 3 PER Pulse™ Recaps will focus on treatment and sequencing decisions for patients with PDAC. Below are some highlights from the activity.
 
PDAC is considered one of the most chemoresistant cancers, due in part to the dense stromal environment and the heterogeneity of associated genetic mutations. Most of the available treatments offer palliation, with a goal of symptom relief and prolonging survival, where possible. Surgery, radiation, chemotherapy, immunotherapy, and targeted agents comprise the current treatment paradigm.1
 
Clinical debate is ongoing regarding the role of adjuvant versus neoadjuvant therapy for patients with pancreatic cancer. In certain patients with resectable pancreatic cancer, treatment in the neoadjuvant setting is favored over conventional adjuvant therapy.

“I am biased toward giving neoadjuvant treatment. The advantages are very clear. All patients are candidates for the adjuvant treatment that we know helps, so it makes sense to give that treatment first. In addition, the patients who undergo initial surgery don’t always bounce back from the surgery, so they may not even get their adjuvant treatment. It selects the patients who are most likely to benefit from surgery.”
 — Christopher Crane, MD

“In clearly resectable pancreatic cancer, the conventional way these are managed is resection followed by adjuvant therapy. However, there is clear evidence, particularly for those tumors in the head of the pancreas where a Whipple operation would be needed, that there are advantages to giving chemotherapy upfront.”
 — Michael A. Choti, MD

Metastatic pancreatic cancer is associated with extremely poor prognosis. Sequential treatment may provide a survival benefit for patients.
 
AGEO Trial
Following failure of FOLFIRINOX, the AGEO trial2 showed that a cohort of 57 patients treated with gemcitabine plus nab-paclitaxel achieved median overall survival (mOS) of 8.8 months (95% CI, 6.2-9.7). Median OS since first-line treatment with FOLFIRINOX was 18 months (95% CI, 16-21). Forty percent of patients reported grade ³3 toxicities, with the most common being neutropenia (12%), neurotoxicity (12%), asthenia (8%), and thrombocytopenia (8%).
 
References
  1. Adamska A, Domenichini A, Falasca M. Pancreatic ductal adenocarcinoma: current and evolving therapies. Int J Mol Sci. 2017;18:1338. doi:10.3390/ijms18071338.
  2. Portal A, Pernot S, Arbaud C, et al. Nab-paclitaxel plus gemcitabine for metastatic pancreatic adenocarcinoma after failure of Folfirinox: results of an AGEO multicenter prospective cohort. J Clin Oncol. 2015;33(suppl; abstr 4123).

PER Pulse Recap (3 of 3)

This third of 3 PER Pulse™ Recaps will focus on therapeutic agents under investigation and encouraging potential treatment advances for the future. Below are some highlights from the activity.
 
As research continues to evolve, the improved understanding of PDAC biology will inexorably lead to novel treatment options directed at both the cancer cells and the surrounding microenvironment.1

“I’m a believer in attacking the stroma as part of the armamentarium in pancreatic cancer. I believe that nab-paclitaxel does that. I believe that nanoliposomal irinotecan does that as well.”
 — George P. Kim, MD

Ongoing research in pancreatic cancer is investigating the predictive value of biomarkers, including tumor hyaluronan (HA) levels in patients. Pancreatic ductal adenocarcinoma commonly features a dense desmoplastic stroma with a large accumulation of HA. Hyaluronan has been shown to promote tumor growth in mice and is correlated with unfavorable prognosis in patients with PDAC.2
 
The desmoplastic reaction associated with PDAC cells may also result in chemoresistance by creating a barrier for drugs to penetrate the tumor. Investigators have begun evaluating PDAC stroma as a potential therapeutic target.3
 
PEGPH20 has been shown to degrade HA, potentially improving the access of anticancer agents. A recent randomized phase II study demonstrated that the addition of PEGPH20 to nab-paclitaxel/gemcitabine significantly improved progression-free survival (PFS) compared with nab-paclitaxel/gemcitabine alone in patients with previously untreated metastatic PDAC.4 Median PFS in the HA-high group was 9.2 months (n=49; HR, 0.51 [95% CI, 0.26-1.00]; P =.048) versus 5.2 months in the nab-paclitaxel/gemcitabine group (n=35).
 
In patients with metastatic PDAC, nanoliposomal irinotecan combined with 5-fluorouracil (5-FU) and folinic acid demonstrated both efficacy and a tolerable safety profile. The open-label, randomized, phase III NAPOLI-1 trial5 randomized 417 patients with metastatic PDAC previously treated with gemcitabine-based therapy to receive nanoliposomal irinotecan plus 5-FU and folinic acid (n=117), nanoliposomal irinotecan monotherapy (n=151), or 5-FU plus folinic acid (n=149).
 
Efficacy Results
At the completion of 313 events, median OS was significantly increased to 6.1 months in patients treated with nanoliposomal irinotecan plus 5-FU and folinic acid (95% CI, 4.8-8.9) versus 4.2 months (95% CI, 3.3-5.3) in those treated with 5-FU and folinic acid (hazard ratio [HR], 0.67 [95% CI, 0.49-0.92]; P =.012).5
 
References
  1. Ansari D, Gustafsson A, Andersson R. Update on the management of pancreatic cancer: surgery is not enough. World J Gastroenterol. 2015;21:3157-3165. doi: 10.3748/wjg.v21.i11.3157.
  2. Sato N, Kohi S, Hirata K, et al. Role of hyaluronan in pancreatic cancer biology and therapy: once again in the spotlight. Cancer Sci. 2016;107:569-575. doi: 10.1111/cas.12913.
  3. Giordano G, Pancione M, Olivieri N, et al. Nano albumin bound-paclitaxel in pancreatic cancer: current evidences and future directions. World J Gastroenterol. 2017;23:5875-5886. doi: 10.3748/wjg.v23.i32.5875.
  4. Hingorani SR, Bullock AJ, Seery TE, et al. Randomized phase II study of PEGPH20 plus nab-paclitaxel/gemcitabine (PAG) vs AG in patients (Pts) with untreated, metastatic pancreatic ductal adenocarcinoma (mPDA). J Clin Oncol. 2017;35(suppl; abstr 4008).
  5. Wang-Gillam A, Li CP, Bodoky G, et al. 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. Lancet. 2016;387:545-557. doi: 10.1016/S0140-6736(15)00986-1.
For additional commentary about these topics and others, visit www.gotoper.com to access more resources from the activity, Medical Crossfire®: Navigating Treatment Decisions in Pancreatic Cancer: Key Questions.

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