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 1.0 AMA PRA Category 1 Credit. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Acknowledgment of Commercial Support

This activity is supported by an educational grant from Lexicon Pharmaceuticals, Inc.

Oncology Briefings™: Understanding Carcinoid Syndrome Diarrhea From Diagnosis to Treatment


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

Activity Overview

This activity, Oncology Briefings™: Understanding Carcinoid Syndrome Diarrhea From Diagnosis to Treatment, developed in the Physicians’ Education Resource, LLC, (PER®) established Oncology Briefings™ legacy format, is an online interactive monograph that provides an overview of recent data regarding the management of carcinoid syndrome diarrhea. This presentation features a national thought leader, Michael A. Morse, MD, who provides key insights and presents 2 patient cases with carcinoid syndrome diarrhea who were successfully treated.

Acknowledgment of Commercial Support

This activity is supported by an educational grant from Lexicon Pharmaceuticals, 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 online CME activity is directed toward oncology healthcare professionals involved in the treatment and management of carcinoid syndrome and carcinoid syndrome diarrhea, including medical oncologists, gastroenterologists, endocrinologists, and surgical oncologists. Fellows, nurses, nurse practitioners, physician assistants, and other healthcare professionals involved in the management of patients with carcinoid syndrome are also invited to participate.

Learning Objectives

Upon completion of this activity, you should be better prepared to:

  • Review the pathophysiology of neuroendocrine tumors (NETs) to stratify patients with carcinoid syndrome and its associated symptoms for optimal therapy
  • Assess current and emerging therapeutic options, as well as sequential strategies, for the treatment of patients with NETs who have carcinoid syndrome‒associated diarrhea
  • Describe the importance of a multidisciplinary approach in the management of patients with carcinoid syndrome

Faculty

Michael A. Morse, MD, FACP, MHS
Duke University Medical Center
Durham, NC
 
 
 

Disclosure: Grant/Research Support: Ipsen, Merck, BMS; Speaker’s Bureau: Novartis, Ipsen, Merck, Lexicon, Genentech, Taiho, Celgene

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 or nurse 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®.

PER Pulse™ Recaps

1 of 3
Insight from Michael A. Morse, MD, FACP, MHS – PER Pulse Recap:
Oncology Briefings: Understanding Carcinoid Syndrome Diarrhea From Diagnosis to Treatment

The online continuing medical education activity, Oncology Briefings: Understanding Carcinoid Syndrome Diarrhea From Diagnosis to Treatment, examines the pathophysiology of neuroendocrine tumors (NETs) to stratify patients with carcinoid syndrome and carcinoid syndrome diarrhea. You will assess current and emerging treatment options and consider sequential strategies to successfully manage and treat your patients with carcinoid syndrome diarrhea. Clinical perspective and key insights, including 2 patient cases, are provided by national thought leader Michael A. Morse, MD, FACP, MHS.

This first of 3 PER Pulse Recaps for the activity will focus on current and emerging therapies for carcinoid syndrome diarrhea. Below are some highlights from the activity featuring Dr. Morse.

“Because it’s very clear that serotonin is the major cause of diarrhea in carcinoid syndrome, being able to focus on reducing the amount of serotonin released and/or produced by the tumor has led to new directions in management. Somatostatin analogs reduce the secretion of serotonin from neuroendocrine tumors, but only recently have we had a therapy that allows us to stop the production of serotonin as well.”
— Michael A. Morse, MD, FACP, MHS

Approximately 20% of patients with NETs will present with symptoms of carcinoid syndrome related to excessive hormone secretion. Somatostatin analogues have become the standard initial treatment for controlling the symptoms of carcinoid syndrome, such as diarrhea and flushing, as well as for controlling the growth of the carcinoid tumor itself in patients with advanced disease.1-3 More specifically, octreotide and lanreotide are the cornerstone treatments for most well-differentiated, somatostatin receptor–expressing, metastatic NETs and the menacing symptoms that present with the disease.4-6 However, in all long-term studies, a proportion of patients with carcinoid syndrome (20%-76% in various studies) are not controlled by the highest standard doses of lanreotide or octreotide at some time during treatment.1,3,7,8

Recently, the orphan drug telotristat ethyl, a tryptophan hydroxylase inhibitor that reduces production of serotonin in NET cells, was approved as the first oral treatment for carcinoid syndrome diarrhea in patients with metastatic NETs. This has caused a shift in the treatment paradigm for carcinoid syndrome diarrhea in patients who are inadequately controlled by somatostatin analogue therapy. With this development, patients can now lead active lives not troubled by frequent and debilitating diarrhea and can have an improved quality of life.9,10

References
  1. Kunz PL, Reidy-Lagunes D, Anthony LB, et al; North American Neuroendocrine Tumor Society. Consensus guidelines for the management and treatment of neuroendocrine tumors. Pancreas. 2013;42(4):557-577. doi: 10.1097/MPA.0b013e31828e34a4.
  2. Mota JM, Sousa LG, Riechelmann RP. Complications from carcinoid syndrome: review of the current evidence. Ecancermedicalscience. 2016;10:662. doi: 10.3332/ecancer.2016.662.
  3. Toumpanakis C, Caplin ME. Update on the role of somatostatin analogs for the treatment of patients with gastroenteropancreatic neuroendocrine tumors. Semin Oncol. 2013;40(1):56-68. doi: 10.1053/j.seminoncol.2012.11.006.
  4. Caplin ME, Pavel M, Ćwikla JB, et al; CLARINET Investigators. Lanreotide in metastatic enteropancreatic neuroendocrine tumors. N Engl J Med. 2014;371(3):224-233. doi: 10.1056/NEJMoa1316158.
  5. Rinke A, Müller HH, Schade-Brittinger C, et al; PROMID Study Group. Placebo-controlled, double-blind, prospective, randomized study on the effect of octreotide LAR in the control of tumor growth in patients with metastatic neuroendocrine midgut tumors: a report from the PROMID Study Group. J Clin Oncol. 2009;27(28):4656-4663. doi: 10.1200/JCO.2009.22.8510.
  6. Rubin J, Ajani J, Schirmer W, et al. Octreotide acetate long-acting formulation versus open-label subcutaneous octreotide acetate in malignant carcinoid syndrome. J Clin Oncol. 1999;17:600-606. doi: 10.1200/JCO.1999.17.2.600.
  7. Pokuri VK, Fong MK, Iyer R. Octreotide and lanreotide in gastroenteropancreatic neuroendocrine tumors. Curr Oncol Rep. 2016;18(1):7. doi: 10.1007/s11912-015-0492-7.
  8. Narayanan S, Kunz PL. Role of somatostatin analogues in the treatment of neuroendocrine tumors. Hematol Oncol Clin North Am. 2016;30(1):163-177. doi: 10.1016/j.hoc.2015.09.008.
  9. Anthony L, Ervin C, Lapuerta P, et al. Understanding the patient experience with carcinoid syndrome: exit interviews from a randomized, placebo-controlled study of telotristat ethyl. Clin Ther. 2017;39(11):2158-2168. doi: 10.1016/j.clinthera.2017.09.013.
  10. Masab M, Saif MW. Telotristat ethyl: proof of principle and the first oral agent in the management of well-differentiated metastatic neuroendocrine tumor and carcinoid syndrome diarrhea. Cancer Chemother Pharmacol. 2017;80(6):1055-1062. doi: 10.1007/s00280-017-3462-y.

2 of 3
Insight from Michael A. Morse, MD, FACP, MHS – PER Pulse Recap:
Oncology Briefings: Understanding Carcinoid Syndrome Diarrhea From Diagnosis to Treatment

As a follow-up to the online continuing medical education activity, Oncology Briefings: Understanding Carcinoid Syndrome Diarrhea From Diagnosis to Treatment, this second of 3 PER Pulse Recaps for the activity will focus on the diagnosis and clinical trial findings of FDA-approved therapies for patients with carcinoid syndrome diarrhea. Below are some highlights from the meeting featuring Dr. Morse:

Carcinoid syndrome is usually initially suspected when a patient presents with flushing and diarrhea, with or without a known neuroendocrine tumor. The most frequent initial examination to confirm the diagnosis of carcinoid syndrome is urinary 24-hour 5-hydroxyindoleacetic acid (5-HIAA), which has a sensitivity of 73% to 91% and a specificity of 100%.1,2

“For a long time, we’ve been treating carcinoid syndrome diarrhea with somatostatin analogues, which are long acting, and using short-acting [ones] as needed. Until recently, our options were to increase the dose of the long acting if a person had poor control. That didn’t always work. Now that we have telotristat ethyl approved, it’s become a very important part of our armamentarium.”
— Michael A. Morse, MD, FACP, MHS

Control of symptoms due to carcinoid syndrome refractory to treatment with somatostatin analogues has been reported in 50% to 90% of patients undergoing cytoreductive surgery. With the use of iodine-131 metaiodobenzylguanidine (I-131 MIBG) treatment, 40% to 75% of patients showed clinical improvement.3-5 After I-131 MIBG treatment, patients frequently require either no somatostatin supplemental therapy or lower doses to control symptoms of carcinoid syndrome, with a mean response time of 6 to 15 months and responses lasting up to 39 months.3-5

For patients poorly controlled with somatostatin analogues, telotristat ethyl provides an effective therapeutic option. The pivotal trial for telotristat ethyl is the TELESTAR trial.6,7 This phase III, randomized, placebo-controlled clinical trial looked at patients who were experiencing ≥4 bowel movements (BMs) a day despite a stable dose of a somatostatin analogue. Patients were randomized to placebo or telotristat ethyl 250 mg 3 times a day or a higher dosage of telotristat. There was a 12-week, double-blind treatment period and an open-label extension phase. The primary endpoint was change from baseline in BM frequency per day averaged over 12 weeks. The difference in BM frequency was 0.81 favoring telotristat 250 mg 3 times daily versus placebo at week 12 (P <.001). The mean BM frequency reduction was 1.7 per day for telotristat ethyl (250 mg 3 times daily) compared with 0.9 BMs per day for placebo. Another predefined endpoint was a BM frequency reduction ≥30% from baseline for ≥50% of the double-blind treatment period, and this was observed in 20% and 44% of patients given placebo or telotristat ethyl 250 mg 3 times daily, respectively. Telotristat ethyl also significantly reduced mean urinary 5-HIAA versus placebo at week 12 (P <.001), indicating that telotristat lowers circulating serotonin levels.

The most common adverse events with telotristat that occurred in ˃5% of patients were nausea, headache, flatulence, decreased appetite, pyrexia, and peripheral edema.6 There can be an increase in hepatic enzymes, notably gamma-glutamyl transferase.

References
  1. Soga J, Yakuwa Y, Osaka M. Carcinoid syndrome: a statistical evaluation of 748 reported cases. J Exp Clin Cancer Res. 1999;18(2):133-141.
  2. Feldman JM. Carcinoid tumors and the carcinoid syndrome. Curr Probl Surg. 1989;26(12):835-885. doi: 10.1016/0011-3840(89)90010-5
  3. Khan MU, Morse M, Coleman RE. Radioiodinated metaiodobenzylguanidine in the diagnosis and therapy of carcinoid tumors. Q J Nucl Med Mol Imaging. 2008;52(4):441-454.
  4. Pathirana AA, Vinjamuri S, Byrne C, Ghaneh P, Vora J, Poston GJ. (131)I-MIBG radionuclide therapy is safe and cost-effective in the control of symptoms of the carcinoid syndrome. Eur J Surg Oncol. 2001;27(4):404-408. doi: 10.1053/ejso.2001.1132.
  5. Ezziddin S, Sabet A, Logvinski T, et al. Long-term outcome and toxicity after dose-intensified treatment with 131I-MIBG for advanced metastatic carcinoid tumors. J Nucl Med. 2013;54(12):2032-2038. doi: 10.2967/jnumed.112.119313.
  6. Kulke MH, Hörsch D, Caplin ME, et al. Telotristat ethyl, a tryptophan hydroxylase inhibitor for the treatment of carcinoid syndrome. J Clin Oncol. 2017;35(1):14-23. doi: 10.1200/JCO.2016.69.2780.
  7. Weickert MO, Kaltsas G, Hörsch D, et al. Changes in weight associated with telotristat ethyl in the treatment of carcinoid syndrome. Clin Ther. 2018;40(6):952-962. doi: 10.1016/j.clinthera.2018.04.006.

3 of 3
Insight from Michael A. Morse, MD, FACP, MHS – PER Pulse Recap:
Oncology Briefings: Understanding Carcinoid Syndrome Diarrhea From Diagnosis to Treatment

As a follow-up to the online continuing medical education activity, Oncology Briefings: Understanding Carcinoid Syndrome Diarrhea From Diagnosis to Treatment, this third of 3 PER Pulse Recaps for the activity will focus on the role of multidisciplinary teams (MDTs) in the management of patients with carcinoid syndrome diarrhea. Below are some highlights from the meeting featuring Dr. Morse:

“It’s important to realize that in a patient with carcinoid syndrome diarrhea that they could have other reasons for their diarrhea. Often we’ll have a gastroenterologist involved if we suspect that there is something more than just the serotonin overproduction.”
— Michael A. Morse, MD, FACP, MHS

Clinical management of carcinoid syndrome requires a multidisciplinary approach that involves surgeons, nurse professionals, medical and radiation oncologists, pulmonologists, pathologists, endocrinologists, and interventional radiologists and, at times, gastroenterologists.1 MDTs can lead to improved treatment outcomes in the management of patients with complex conditions. They are associated with improvements in diagnosis, treatment planning, survival, patient satisfaction, clinician satisfaction, and financial efficiency.2

A collaborative study, recently presented at the 12th Annual European Neuroendocrine Tumor Society Conference, evaluated the patient perspective on neuroendocrine tumor (NET) management and interactions with health care professionals. A total of 1928 patients with NETs were recruited and surveyed from more than 12 countries in the Americas, Asia, Europe, and Oceania.3 The study concluded that this first large, global survey of patients with NETs demonstrated the benefits of an MDT approach, including improved satisfaction with care and interactions with health care professionals and a more positive and informed perspective regarding NETs.3

Although patients typically traveled significantly greater distances to visit NET specialist centers, they had an overall better experience, which included discussing a variety of topics with their physicians, such as number of medical tests conducted per year, quality of and access to treatments, and access to other informed health care professionals.3 Despite improvements seen with MDTs, the survey highlighted unmet needs in the management of NETs. An estimated 40% of patients visiting NET specialist centers did not feel that their health care professionals worked as a well-coordinated team, which demonstrates room for improvement in medical team interactions.3

The impact of MDT care is even more important in rare cancers such as NETs. Given that the knowledge may be confined to certain practicing physicians or centers where patients with these diseases are treated more often, creation of a dedicated MDT can lead to more informed treatment and management decisions for these patients.2

References
  1. Filosso PL, Ferolla P, Guerrera F, et al; European Society of Thoracic Surgeons Lung Neuroendocrine Tumors Working-Group Steering Committee. Multidisciplinary management of advanced lung neuroendocrine tumors. J Thorac Dis. 2015;7(suppl 2):S163-S171. doi: 10.3978/j.issn.2072-1439.2015.04.20.
  2. Singh SC, Law C. Multidisciplinary reference centers: the care of neuroendocrine tumors. J Oncol Pract. 2010;6(6):e11-e16. doi: 10.1200/JOP.2010.000098.
  3. Öberg K, Leyden J, Sissons M, et al. Multidisciplinary team in neuroendocrine tumor management: results from the first global NET patient survey – a collaboration between the International Neuroendocrine Cancer Alliance (INCA) and Novartis Pharmaceuticals. Presented at the 12th Annual European Neuroendocrine Tumor Society Conference; March 11-13, 2015; Barcelona, Spain. Abstract 1208.
    engonetuf.blob.core.windows.net/assets/uploads/files/ENETS_MDT_NETPtSurvey_FNL.pdf.

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