Treatment Sequencing Strategies in Advanced Neuroendocrine Tumors: A Review

Abstract

Neuroendocrine tumor (NET) incidence has grown. The treatment landscape for advanced NETs is rapidly evolving, but there are limited head-to-head data to guide treatment sequencing decisions. We assessed the available clinical data to aid practicing clinicians in their routine clinical decision-making. Clinical trials have demonstrated efficacy benefits for new therapies in advanced NETs. Emerging long-term data from these trials have enabled clinicians to make more accurate risk-benefit assessments, particularly for patients receiving multiple lines of therapy. However, clinical data specifically regarding treatment sequencing are limited. In lieu of definitive data, treatment sequencing should be based on disease-related factors (e.g., site of tumor origin, volume of disease) and patient-related characteristics (e.g., comorbidities, patient preferences). Clinical decision-making in advanced NETs remains highly individualized and complex; important evidence gaps regarding treatment sequencing remain. Given this, advanced NET management should be a joint effort of multidisciplinary teams at referring and high-volume centers. Additional clinical trial and real-world evidence are needed to meet the challenge of understanding how to sequence available NET therapies. Until these trials are conducted, the best practices provided in this review may serve as a guide for clinicians making treatment sequencing decisions based on the available data.

Non-Interventional Management of Advanced Pancreatic Neuroendocrine Neoplasms in Patients with von Hippel-Lindau Disease

“…Two parameters should be calculated into the decision making. First, the accumulating toxicity to the bone marrow [ 55 ], due to the potential need for chemotherapy later in the patient’s life course [ 56 ]. Second, in VHL there is a unique goal to enable “normal life” alongside the management of cancer, whenever feasible.…”

Tumour Heterogeneity and the Consequent Practical Challenges in the Management of Gastroenteropancreatic Neuroendocrine Neoplasms

“…The evaluation of tumour heterogeneity could also be particularly useful in guiding treatment selection at diagnosis and following recurrence, as outcomes could be improved by targeting different components of the disease. The choice of subsequent treatment should be based on tumour biology at the time of recurrence or progression [ 200 , 201 ]. For pancreatic NENs, where outcomes are generally favourable but relapse common in advanced cases, tailored treatment sequencing strategies could help in selecting the most effective treatment option for each particular case [ 202 ].…”

Critical updates in neuroendocrine tumors: Version 9 American Joint Committee on Cancer staging system for gastroenteropancreatic neuroendocrine tumors

“…3 Consequently, an increased focus on the research and clinical care specific to NETs has resulted in a broader depth of NETs, including epidemiology, pathologic classification, staging criteria, patient outcomes, diagnostics, and therapeutic drug development (Figure 1). [4][5][6] The American Joint Committee on Cancer (AJCC) staging system is an internationally recognized standard for cancer staging and is periodically revised by disease-specific expert panels. These updates are necessary to highlight evidence-based prognostic factors and guide optimal management.…”

“…Consequently, an increased focus on the research and clinical care specific to NETs has resulted in a broader depth of NETs, including epidemiology, pathologic classification, staging criteria, patient outcomes, diagnostics, and therapeutic drug development (Figure 1). 4–6 …”