Multidisciplinary Treatment Strategies for Well-Differentiation Neuroendocrine Tumors

Jonathan Strosberg, MD

Jonathan Strosberg, MD

Multidisciplinary treatment is of great importance when managing neuroendocrine tumors (NETs), which are heterogenous and have dominance in different gastrointestinal organs, explained Jonathan Strosberg, MD, who presented on the subject at the 5th Annual School of Gastrointestinal Oncology (SOGO 2020).

Using the case of a 66-year-old patients who presented with first abdominal pain and infrequent vomiting, Strosberg reviewed the available treatment options for liver dominant disease, which include systematic treatments, somatostatin analogs (SSAs), as well as new targeted therapies like sunitinib (Sutent) and everolimus (Afinitor).

Satisfactory progression-free survival (PFS) data on SSAs are seen in the phase III PROMID study (NCT00171873) and the phase III CLARINET study (NCT003534960). In PROMID, the median PFS observed with the SSA octreotide acetate (Sandostatin) was 14.3 months (95% CI, 11.0-28.8) compared with 6.0 months with placebo (95% CI, 3.7-9.4). The hazard ratio (HR) for this comparison was 0.34 (95% CI, 0.20-0.59;P=.000072). In the CLARINET study, the median PFS was not reached with lanreotide (Somatuline) and was 18.0 months in the placebo group (HR 0.47; 95% CI, 0.3-0.73; P=.0002).

It was noted that the pros of using SSAs are that these agents are well-tolerated, low risk, have supporting evidence of efficacy and safety, and are palliative for patients with functional tumor syndromes. On the other hand, SSAs have a low radiographic response rate (<1%), and most of the evidence around the activity of SSAs is related to indolent tumors.

Evidence around targeted therapies offers more variety in terms of tumor characteristics. For example, the RADIANT studies (NCT00363051, NCT00412061, and NCT00510068) showed positive PFS data for patients with advanced NET with a history of carcinoid syndrome, advanced pNET, and advanced NET, with no history of carcinoid syndrome. These studies also provided the same information for overall survival. Based on these studies, Strosberg suggested that everolimus has benefit for NETs with the exception of midgut NETs/carcinoid syndrome. In addition, elderly patients would require heavy monitoring while taking the drug.

Comparing everolimus with sunitinib for treatment of pancreatic NETs, it was determined that everolimus is favorable for more patients because it can be used with comorbidities that sunitinib cannot. Other targeted therapies like temozolomide (Temodar), and combinations like temozolomide plus capecitabine have shown promising activity and safety. The areas for improvement with these agents include the number of unpredictable grade 3/4 cytopenias, which occur in 15% of patients, and identifying clear predictive markers.

In an interview withTargeted Oncologyat SOGO 2020, Strosberg, associate professor, Gastrointestinal Oncology Program, Moffitt Cancer Center, explained the importance of having multidisciplinary teams when treating patients with NETs.

TARGETED ONCOLOGY: Can you discuss the relevance of multidisciplinary treatment for neuroendocrine tumors?

Strosberg: NETs, more than any other cancer, rely on multidisciplinary treatments. For liver dominant disease, interventional radiology plays an important role both in tumor reduction and managing symptoms. One of the most important systemic therapies is peptide receptor radiotherapy with radiolabeled somatostatin analog treatment, and that is done by nuclear medicine.

Heart disease is an important consequence of carcinoid syndrome, and cardiologists and cardiac surgeons treat these conditions.

Even in stage 4 setting, surgeons play an important role. If complete curative surgery can't be achieved, there's still a benefit to cytoreductive surgery, which is not the case for most other cancers. Because of their natural history of having relatively slow growth, we can reduce a great deal of disease, and it can be years before things start going again. This is why surgery and other disciplines play an important role.

TARGETED ONCOLOGY: At your center, how do physicians from various disciplines interact to treat patients?

Strosberg: In my center, I see most of the patients with NETs. Based on the patients' individual circumstances, I consult with various specialties.

Most other institutions have a multidisciplinary tumor board where complex cases can be discussed. Also, in other institutions, there are multidisciplinary clinics that are set up specifically for neuroendocrine tumors. These clinics have the medical oncologist, surgeon, and interventional radiologist seeing the patient at the same time. Different institutions have different practices.

TARGETED ONCOLOGY: In the community setting, when and why is it important to refer patients with neuroendocrine tumors to larger center for treatment?

Strosberg: NETs are rare. Unlike colorectal cancer, breast cancer, and lung cancer, it's not a malignancy that most community oncologists have experience with. NET is also an extremely heterogeneous cancer. Almost no NET case is alike. It can arise in many different organs, and the spectrum of aggressiveness is from the slowest growing solid tumors to the fastest growing. Also, the treatment can be complex depending on whether it's liver dominant or not, the differentiation grade, stage, and somatostatin receptor expression. There are also some complexities that make it preferable for the patients at least get a consultation.

TARGETED ONCOLOGY: Can you discuss the presentation you gave on multidisciplinary treatment of neuroendocrine tumor at SOGO?

Strosberg: I gave an overview of the different treatments for NETs. I discussed somatostatin analogs as first-line therapy for control of symptoms as well as stabilization of tumor growth, newer medications for NETs, like sunitinib, and then I focused on peptide receptor radiotherapy as well as liver-directed therapies.

TARGETED ONCOLOGY: What is the key take away from your presentation?

Strosberg: We have multiple treatments that have emerged in the past decade, but few studies compare these treatments to each other. The goal is to try to find out what treatment should be used where, what are the absolute or counter-indications to treatment, and which factors should be considered.

Reference:

Strosberg, Jonathan. Multidisciplinary Management of Well-Differentiated NETs. Presented at the 5th Annual School of Gastrointestinal Oncology; March 21, 2020; Virtual Conference.