Neuroendocrine Tumours, Gastrointestinal Oncology, Liver Cancer, Pancreatic Cancer CME ACCREDITED Watch Time: 36 mins

touchPANEL DISCUSSION Perspectives on the current status and recent advances in GEP-NETs

Explore current perspectives on the management of GEP-NETs through this panel discussion, highlighting emerging data presented at the ESMO Congress 2021.

Prof. Jonathan R Strosberg

Moffitt Cancer Center, Tampa, FL, USA

CHAIR

Panelists:
Dr Jennifer Chan, Prof. Dr. med. Marianne Pavel
 
Video Chapters
Introduction

Medical oncologist, Prof. Jonathan Strosberg (Chair), introduces the panel and outlines the agenda for discussion on gastroenteropancreatic neuroendocrine tumours (GEP-NETs), with a focus on recent data presented at the ESMO Congress 2021.

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1/4 Next Chapter
 
Treatment options for patients with GEP-NETs: Where are we now?

In the context of the rising incidence of neuroendocrine tumours, the panel discusses current treatment options and looks at the latest data for tyrosine kinase inhibitors and PRRT approaches in well-differentiated GEP-NETs.

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2/4 Next Chapter
 
Innovation and integration: Do we need to adapt existing guidelines?

The panel reviews the emerging therapeutic agents for GEP-NETs, and goes on to discuss the implications of the latest data on immunotherapy, including in patients with poorly-differentiated GEP-NETs.

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3/4 Next Chapter
 
Progression and treatment response: Towards an individualized approach

The panel discusses the need for a more individualized approach to the management of patients with GEP-NETs, including when to use functional imaging to evaluate progression.

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Overview & Learning Objectives
Overview

Join leading experts as they discuss current perspectives and recent advances in the treatment and monitoring of gastroenteropancreatic neuroendocrine tumours, encompassing emerging data presented at the ESMO Congress 2021.

This activity is jointly provided by USF Health and touchIME. read more

Target Audience

Oncologists, gastroenterologists, radiologists and endocrinologists involved in the management of gastroenteropancreatic neuroendocrine tumours.

Disclosures

All individuals in a position to influence content have disclosed to USF Health any financial relationship with an ineligible organization. USF Health has reviewed and mitigated all relevant financial relationships related to the content of the activity. The relevant relationships are listed below. All individuals not listed have no relevant financial relationships.

Faculty

Prof. Jonathan R Strosberg discloses: Consultancy fees from Novartis. Grants/research support fees from Novartis. Speaker fees from Ipsen.

Dr Jennifer Chan discloses: Advisory board/panel fees from Advanced Accelerator Applications (relationship terminated). Consultancy fees from Advanced Accelerator Applications, Lexicon, Ipsen (relationships terminated), TerSera. Stock/shareholder (self-managed) Merck.

Prof. Dr. med. Marianne Pavel discloses: Advisory board and consultancy fees from Advanced Accelerator Applications, Boehringer Ingelheim, Ipsen, Lilly, Merck Sharp & Dohme and Riemser Pharma GmbH.

Content reviewer

Olivia Renee Pane, PharmD, CDCES, has no relevant financial relationships to disclose.

Touch Medical Director

Kathy Day has no financial interests/relationships or affiliations in relation to this activity.

USF Health Office of Continuing Professional Development and touchIME staff have no financial interests/relationships or affiliations in relation to this activity.

Requirements for Successful Completion

In order to receive credit for this activity, participants must review the content and complete the post-test and evaluation form. Statements of credit are awarded upon successful completion of the post-test and evaluation form.

If you have questions regarding credit please contact cpdsupport@usf.edu 

Accreditations

Physicians

This activity has been planned and implemented in accordance with the accreditation requirements and policies of the Accreditation Council for Continuing Medical Education (ACCME) through a joint providership of USF Health and touchIME. USF Health is accredited by the ACCME to provide continuing medical education for physicians.

USF Health designates this enduring material for a maximum of 0.75 AMA PRA Category 1 CreditTM.  Physicians should claim only the credit commensurate with the extent of their participation in the activity.

The European Union of Medical Specialists (UEMS) – European Accreditation Council for Continuing Medical Education (EACCME) has an agreement of mutual recognition of continuing medical education (CME) credit with the American Medical Association (AMA). European physicians interested in converting AMA PRA Category 1 CreditTM into European CME credit (ECMEC) should contact the UEMS (www.uems.eu)

Advanced Practice Providers

Physician Assistants may claim a maximum of 0.75 Category 1 credits for completing this activity. NCCPA accepts AMA PRA Category 1 CreditTM from organizations accredited by ACCME or a recognized state medical society.

The AANPCP accepts certificates of participation for educational activities approved for AMA PRA Category 1 CreditTM by ACCME-accredited providers. APRNs who participate will receive a certificate of completion commensurate with the extent of their participation.

Date of original release: 28 October 2021. Date credits expire: 28 October 2022.

If you have any questions regarding credit please contact cpdsupport@usf.edu

Learning Objectives

After watching this activity, participants should be better able to:

  • Interpret the data supporting new and emerging treatment options to improve outcomes for patients with GEP-NETs
  • Analyse current guidelines for the therapeutic agents to treat GEP-NETs
  • Appraise the criteria for assessing disease progression in GEP-NETs, and how they impact treatment choice
Faculty & Disclosures
Prof. Jonathan R Strosberg

Moffitt Cancer Center, Tampa, FL, USA

Prof. Jonathan Strosberg is Professor at the Moffitt Cancer Center, specializing in the management of neuroendocrine malignancies. He is a graduate of Harvard University and Cornell University Medical College. He completed his fellowship at the Moffitt Cancer Center, leads the NET division at Moffitt, and heads the GI department research programme. read more

Prof. Strosberg has published over 150 articles and book chapters on the diagnosis and management of neuroendocrine malignancies, including first-author publications in the New England Journal of Medicine, Journal of Clinical Oncology, Clinical Cancer Research, Annals of Oncology, Annals of Surgery and Cancer. He has authored 12 articles for UptoDate.

Prof. Strosberg is vice chair of the North American Neuroendocrine Tumor Society (NANETS), serves on the neuroendocrine guidelines committee of the National Comprehensive Cancer Network (NCCN), serves on the neuroendocrine task force of the National Cancer Institute (NCI), and co-chairs the Neuroendocrine Tumor section of Southwest Oncology Group (SWOG).

Prof. Jonathan R Strosberg discloses: Consultancy fees from Novartis. Grants/research support fees from Novartis. Speaker fees from Ipsen.

Dr Jennifer Chan

Dana-Farber Cancer Institute, Boston, MA, USA

Jennifer Chan, MD, MPH is Assistant Professor of Medicine at Harvard Medical School, and Senior Physician in the Division of Medical Oncology at Dana-Farber Cancer Institute in Boston, USA. read more

Dr Chan is the Director of the Neuroendocrine and Carcinoid Tumors Program, and Clinical Director for the Gastrointestinal Cancer Center at the Dana-Farber/Brigham and Women’s Cancer Center, where her clinical practice focuses on the care of patients with neuroendocrine tumours and gastrointestinal cancers.

She has been principal investigator of multiple clinical trials investigating novel therapies for neuroendocrine tumours, and has been involved in studies examining factors associated with clinical outcomes in patients with neuroendocrine tumours.

Dr Jennifer Chan discloses: Advisory board/panel fees from Advanced Accelerator Applications (relationship terminated). Consultancy fees from Advanced Accelerator Applications, Lexicon, Ipsen (relationships terminated), TerSera. Stock/shareholder (self-managed) Merck.

Prof. Dr. med. Marianne Pavel

Friedrich Alexander University of Erlangen-Nürnberg, Erlangen, Germany

Prof. Dr. med. Marianne Pavel is a senior physician and current Chair of the Division of Endocrinology at the Friedrich Alexander University of Erlangen-Nürnberg, Erlangen in Germany. read more

In April 2020, Prof. Dr. med. Pavel was appointed as President of The European Neuroendocrine Tumor Society (ENETS). She is first author on key ENET guidelines issued in 2012, and updated in 2016.

Prof. Dr. med. Pavel is actively involved in clinical research, and she helped establish one of the first ENETS Centers of Excellence at the Charité University Hospital in Berlin. She continues to lead key trials in the field of neuroendocrine tumours.

Prof. Dr. med. Marianne Pavel discloses: Advisory board and consultancy fees from Advanced Accelerator Applications, Boehringer Ingelheim, Ipsen, Lilly, Merck Sharp & Dohme and Riemser Pharma GmbH.

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Question 1/5
Which of the following statements best summarizes the findings from the NIPINEC trial (NCT03591731), evaluating the efficacy and safety of immunotherapy in GEP-NETs, that were recently presented at ESMO 2021?

ESMO, European Society for Medical Oncology; GEP, gastroenteropancreatic; NET, neuroendocrine tumour; ORR, objective response rate.
Correct

Findings from the NIPINEC trial (NCT03591731) were presented at ESMO 2021. The study evaluated the efficacy and safety of single-agent nivolumab compared with combination nivolumab plus ipilimumab as second- or third-line therapy in patients with lung- and GEP-NETs who had received at least one prior line of platinum-based chemotherapy. In the GEP-NET cohort (n=93), the primary endpoint (8-week ORR >10%) was achieved with combination nivolumab plus ipilimumab, but not with single-agent nivolumab (8-week ORR: 11.6% vs 7.1%, respectively).

Abbreviations

ESMO, European Society for Medical Oncology; GEP, gastroenteropancreatic; NET, neuroendocrine tumour; ORR, objective response rate.

Reference

Girard N, et al. Ann Oncol. 2021;32(Suppl. 5):S1283–346.

Question 2/5
Your patient, with a well-differentiated, grade 2, functional midgut NET with high SSTR expression, shows signs of progression on first-line SSA therapy at follow-up. Guided by the PFS data for approved agents in midgut NETs, which of the following options might you consider next for the treatment of this patient?

LAR, long-acting release; NET, neuroendocrine tumour; PFS, progression-free survival; SSA, somatostatin analogue; SSTR, somatostatin receptor.
Correct

177Lu-DOTATATE and octreotide LAR are approved for the treatment of SSTR-positive GEP-NETs, including midgut NETs, in adult patients.1–4 In the NETTER-1 phase III trial, treatment with 177Lu-Dotatate prolonged PFS compared with high-dose octreotide LAR amongst patients with advanced midgut NETs. The median PFS in the octreotide LAR cohort was 8.4 months (95% CI 5.8–9.1), and not yet reached at time of analysis in the 177Lu-Dotatate cohort. Treatment with 177Lu-Dotatate represented a 79% lower risk of disease progression or death compared with high-dose octreotide LAR (HR for disease progression or death with 177Lu-Dotatate vs octreotide LAR: 0.21, 95% CI 0.13–0.33; p<0.001). Subgroup analyses showed consistent benefit across major subgroups.5

Final OS data from the NETTER-1 trial, at >6.3 years’ median follow-up (recently presented at ESMO 2021) were equivocal. Although not statistically significant, the gain in OS of almost 12 months represents a meaningful benefit with 177Lu-DOTATATE. Results may have been confounded by the number of patients who crossed over to PRRT from SSA, and the relatively small number of patients in the trial. The good safety profile and quality of life benefit makes this an effective second-line treatment for these patients.6

Although everolimus is used for the treatment of progressive NETs of gastrointestinal origin, it is only indicated in the treatment of tumours that are non-functional.7,8

Sunitinib is approved for the treatment of progressive, well-differentiated pancreatic NETs in adult patients with unresectable, locally advanced or metastatic disease, and is not currently indicated in extrapancreatic NETs.9,10

Abbreviations

CI, confidence interval; ESMO, European Society for Medical Oncology; GEP, gastroenteropancreatic; HR, hazard ratio; LAR, long-acting release; NET, neuroendocrine tumour; OS, overall survival; PFS, progression-free survival; PRRT, peptide receptor radionuclide therapy; SSA, somatostatin analogue; SSTR, somatostatin receptor.

References

  1. US FDA. Prescribing information: 177Lu-DOTATATE. 2020. Available at: www.accessdata.fda.gov/drugsatfda_docs/label/2020/208700s010lbl.pdf (accessed October 2021).
  2. EMA. Summary of product characteristics: 177Lu-DOTATATE. 2021. Available at: www.ema.europa.eu/en/documents/product-information/lutathera-epar-product-information_en.pdf (accessed October 2021).
  3. US FDA. Prescribing information: octreotide LAR. 2021. Available at: www.accessdata.fda.gov/drugsatfda_docs/label/2021/021008s041lbl.pdf (accessed October 2021).
  4. EMA. Summary of product characteristics: octreotide LAR. Available at: www.ema.europa.eu/en/documents/referral/sandostatin-lar-article-30-referral-annex-iii_en.pdf (accessed October 2021).
  5. Strosberg J, et al. N Engl J Med. 2017;376:125–35.
  6. Ruszniewski PB, et al. Ann Oncol. 2021;32(Suppl. 5):S911–2.
  7. US FDA. Prescribing information: everolimus. 2020. Available at: www.accessdata.fda.gov/drugsatfda_docs/label/2020/022334s044,203985s016lbl.pdf (accessed October 2021).
  8. EMA. Summary of product characteristics: everolimus. 2021. Available at: www.ema.europa.eu/en/documents/product-information/afinitor-epar-product-information_en.pdf (accessed October 2021).
  9. US FDA. Prescribing information: sunitinib. 2021. Available at: www.accessdata.fda.gov/drugsatfda_docs/label/2020/021938s037lbl.pdf (accessed October 2021).
  10. EMA. Summary of product characteristics: sunitinib. 2021. Available at www.ema.europa.eu/en/documents/product-information/sutent-epar-product-information_en.pdf (accessed October 2021).
Question 3/5
While on TKI therapy for progressive disease, your patient with a known SSTR-positive, advanced, grade 2, well-differentiated pancreatic NET reports increasing discomfort with bone pain that has gradually worsened over recent months. You suspect that bone metastases may now be present. Which of the following imaging modalities would best assess the presence of bone metastases in this patient?

CT, computed tomography; DEXA, dual-energy X-ray absorptiometry; FDG, fluorodeoxyglucose; NET, neuroendocrine tumour; PET, positron emission tomography; SSTR, somatostatin receptor; TKI, tyrosine kinase inhibitor.
Correct

Whole-body MRI and functional imaging with 68Ga-DOTATATE/PET-CT may be considered for evaluating bone metastases in patients with well-differentiated NETs.1 Both conventional and functional imaging techniques are commonly used for the diagnosis of bone metastases in patients with NETs. 68Ga-DOTATATE/PET-CT has good diagnostic accuracy to detect distant metastases, including bone metastases, and may have a significant impact on patient management.1–4

DEXA scans have been used to evaluate changes in bone mineral density in patients with functional NETs for research purposes,5 but are not a recommended method for determining bone metastases. Recent consensus statements suggest that 18F-FDG PET should be limited to patients with SSTR-negative NETs.1

Abbreviations

CT, computed tomography; DEXA, Dual-energy X-ray absorptiometry; FDG, fluorodeoxyglucose; MRI, magnetic resonance imaging; NET, neuroendocrine tumour; PET, positron emission tomography; SSTR, somatostatin receptor.

References

  1. Merino-Casabiel X, et al. Clin Transl Oncol. 2018;20:1522–8.
  2. Sanli Y, et al. AJR. 2018;211:267–77.
  3. Cives M, et al. Neuroendocrinology. 2021;111:207–16.
  4. Morse B, et al. Curr Treat Opt Oncol. 2020;21:75.
  5. Walsh JS, et al. J Clin Endocrinol Metab. 2013;98:2902–7.
Question 4/5
You are consulted for evaluation of an incidentally detected, 8 mm, low-grade NET in the duodenal bulb. The patient’s local physician requested a CgA test, which revealed elevated levels of CgA in this patient. Which of the following statements is most accurate?

CgA, chromogranin A; NET, neuroendocrine tumour; PPI, proton pump inhibitor.
Correct

Appraising the utility of CgA, current guidelines acknowledge the conflicting clinical evidence surrounding the predictive and prognostic value of CgA as a biomarker in NETs. Guidelines highlight that CgA may be elevated due to non-NET related factors: CgA is known to be elevated in patients with renal or hepatic impairment, and in patients receiving PPIs.1 CgA is not recommended as a singular diagnostic test in isolation due to its limitations.1,2 Data from recent studies identified an early decrease of CgA levels after treatment as a possible favourable prognostic factor.3

Abbreviations

CgA, chromogranin A; NET, neuroendocrine tumour; PPI, proton pump inhibitor.

References

  1. National Comprehensive Cancer Network. NCCN Guidelines Version 1.2021: Neuroendocrine and Adrenal Tumors [Discussion update in progress].
    Available at: www.nccn.org/guidelines/guidelines-detail?category=1&id=1448  (accessed July 2021).
  2. Baekdel J, et al. Diagnostics. 2020;10:881.
  3. Massironi S, et al. JOP. 2018;(Suppl. 3):371–9.
Question 5/5
Regarding novel radionuclide therapies for GEP-NETs, which of the following best describes the basic characteristics of alpha-emitting particles, compared with conventional beta-emitters?

dsDNA, double-stranded DNA; GEP, gastroenteropancreatic; NET, neuroendocrine tumour.
Correct

Alpha particles have higher particle energy (5–9 MeV), shorter pathlength (40–100 μm) and greater linear energy transfer (~80 keV/μm), compared with beta-particle energy (50–2,300 keV), pathlength (0.05–12 mm) and linear energy transfer (~0.2 keV/μm). Alpha-particles create a high ionisation density, causing a high number of dsDNA breaks compared with beta-particles, which have a lower ionisation density.

Abbreviations

dsDNA, double-stranded DNA; eV, electronvolt; GEP, gastroenteropancreatic; NET, neuroendocrine tumour.

Reference

Navalkissoor S, Grossman A. Neuroendocrinology. 2019;108:256–64.

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