Systemic Therapy for Tumor Control in Metastatic Well-Differentiated Gastroenteropancreatic Neuroendocrine Tumors: ASCO Guideline

Abstract

PURPOSE To develop recommendations for systemic therapy for well-differentiated grade 1 (G1) to grade 3 (G3) metastatic gastroenteropancreatic neuroendocrine tumors (GEP-NETs). METHODS ASCO convened an Expert Panel to conduct a systematic review of relevant studies and develop recommendations for clinical practice. RESULTS Eight randomized controlled trials met the inclusion criteria for the systematic review. RECOMMENDATIONS Somatostatin analogs (SSAs) are recommended as first-line systemic therapy for most patients with G1-grade 2 (G2) metastatic well-differentiated GI-NETs. Observation is an option for patients with low-volume or slow-growing disease without symptoms. After progression on SSAs, peptide receptor radionuclide therapy (PRRT) is recommended as systematic therapy for patients with somatostatin receptor (SSTR)–positive tumors. Everolimus is an alternative second-line therapy, particularly in nonfunctioning NETs and patients with SSTR-negative tumors. SSAs are standard first-line therapy for SSTR-positive pancreatic (pan)NETs. Rarely, observation may be appropriate for asymptomatic patients until progression. Second-line systemic options for panNETs include PRRT (for SSTR-positive tumors), cytotoxic chemotherapy, everolimus, or sunitinib. For SSTR-negative tumors, first-line therapy options are chemotherapy, everolimus, or sunitinib. There are insufficient data to recommend particular sequencing of therapies. Patients with G1-G2 high-volume disease, relatively high Ki-67 index, and/or symptoms related to tumor growth may benefit from early cytotoxic chemotherapy. For G3 GEP-NETs, systemic options for G1-G2 may be considered, although cytotoxic chemotherapy is likely the most effective option for patients with tumor-related symptoms, and SSAs are relatively ineffective. Qualifying statements are provided to assist with treatment choice. Multidisciplinary team management is recommended, along with shared decision making with patients, incorporating their values and preferences, potential benefits and harms, and other characteristics and circumstances, such as comorbidities, performance status, geographic location, and access to care. Additional information is available at www.asco.org/gastrointestinal-cancer-guidelines .

Diagnostic and Therapeutic Management of Primary Orbital Neuroendocrine Tumors (NETs): Systematic Literature Review and Clinical Case Presentation

“…This is except for one patient who presented with leptomeningeal spreading four years after the first diagnosis; the typical attitude of these neoplasms is of locoregional involvement with no distant metastases described. Currently, we are unable to produce a clear recommendation regarding follow up-management, but we suggest that clinical and radiological evaluations with MRI and PET/CT are performed for at least 5 years, according to national and international oncological guidelines [84,105,106].…”

Systemic Therapy for Tumor Control in Well-Differentiated Metastatic Gastroenteropancreatic Neuroendocrine Tumors: ASCO Guideline Q and A

“…For some examples of these centers, see the author affiliations in the full ASCO guideline publication. 1…”

“…In 2023, ASCO published a guideline on systemic therapy for tumor control in welldifferentiated metastatic grade 1 to grade 3 (G1-G3) GI and pancreatic neuroendocrine tumors (GEP-NETs; Fig 1). 1 This companion Q and A article addresses some of the questions that clinicians may face as they implement the recommendations into clinical practice. ASCO plans to address recommendations on the topic of symptom control of GEP-NETs in a forthcoming guideline.…”

Advances in Radionuclide Therapies for Patients with Neuro-endocrine Tumors

“…Surgical resection of the primary tumor and regional lymph nodes is still the only curative treatment; however, more than 40% of patients initially present with metastatic and advanced disease. At this stage, the disease is considered non-curative, so treatment focusses on controlling tumor volume, reduce tumor related side-effects, improve quality of live (QoL), and prolong survival [ 1 , 2 ]. In patients with advanced well-differentiated somatostatin-receptor (SSTR) positive (functional) NETs, somatostatin analogs (SSA) are generally recommended as first-line treatment.…”

“…Despite extensive data on disease control using PRRT in (retrospective) clinical cohorts, therapeutic efficacy over standard-of-care (SSA) was proven in the phase 3 randomized controlled trial, NETTER-1 [ 5 •]. The benefit in QoL and progression-free survival after PRRT plus SSA over high-dose SSA-alone led to regulatory approvals and implementation of PRRT into earlier treatment lines in the recent guidelines [ 2 , 6 ].…”