As a result of the COVID-19 pandemic, year 2020 has witnessed unprecedented changes in the practice of medicine and dissemination of treatment advances presented in scientific forums. Adapting to the changes, organizations such as the American Society of Clinical Oncology (ASCO), the European Society for Medical Oncology (ESMO), and the North American Neuroendocrine Tumor Society (NANETS) have adopted abbreviated virtual formats for their national and international meetings that delivered cutting-edge research in the advancement of oncology care. Recognizing the challenges of the virtual format in terms of reach and impact, we are bringing the Year in Review series that seeks to synthesize the presented treatment advances and distribute the information to clinicians in a timely and effective manner to support cancer care delivery and research.
This edition of Year in Review is focused on neuroendocrine tumors (NETs), which are rare heterogeneous neoplasms that undergo neuroendocrine differentiation and arise in many organs of the body, but predominantly in the gastrointestinal tract, pancreas, or lung. Below is a quick review of some of the topics discussed in this issue.
Somatostatin analogs, including octreotide and lanreotide and their different formulations, are the cornerstone of therapy for patients with NETs in the management of symptoms of excessive hormone secretion. Results of the prospective international phase 2 CLARINET FORTE study concluded that escalating lanreotide autogel (LAN) dosing frequency (120 mg every 14 days) may be a viable management strategy to be considered before switching to an alternative treatment. The multicenter phase 2 ATLANT study concluded that LAN plus temozolomide combination therapy may represent a potential treatment option for the management of patients with progressive thoracic NETs. Results of the international, placebo-controlled, randomized phase 2 REMINET trial indicate that maintenance treatment with LAN following first-line chemotherapy may provide clinical benefit in aggressive grade 1 and 2 well-differentiated duodeno-pancreatic NETs. In the absence of head-to-head comparative data between octreotide long-acting release (LAR) and lanreotide, findings of a single-institution retrospective study suggest that first-line octreotide LAR and lanreotide treatment was associated with similar survival outcomes and biochemical response in patients with metastatic well-differentiated gastroenteropancreatic NETs.
Peptide receptor radionuclide therapy (PRRT) using 177Lu-DOTA-Tyr3-octreotate (177Lu-DOTATATE) is an integral component of the management of well-differentiated unresectable or metastatic NETs. Initial results of the phase 2 Australasian Gastrointestinal Trials Group (AGITG) CONTROL NET study indicated that addition of capecitabine/temozolomide to the standard PRRT platform was active in patients with pancreatic and updated midgut NETs. Results of the US expanded access program in patients with advanced NETs showed that the safety profile of 177Lu-DOTATATE treatment in a real-world population was consistent with those previously described in clinical trials.
There is continued interest in identifying novel targets and strategies for therapeutic intervention, with results of several such efforts presented at these meetings, including the multitargeted tyrosine kinase inhibitors surufatinib and cabozantinib, as well as immunotherapy. Data from exploratory analysis of the SANET-ep trial indicated that the demonstrated efficacy benefits of surufatinib therapy in Chinese patients with advanced extrapancreatic NETs also extended to major subgroups by Ki-67 and primary tumor origins and did not compromise health-related quality of life. Results of a dose-escalation expansion study confirmed the efficacy and safety of surufatinib in the US patient population with progressive NETs. An ongoing phase 2 study (NCT04412629) is evaluating the efficacy and safety of cabozantinib in patients with high-grade neuroendocrine neoplasms. While the demonstrated activity of immunotherapy in other tumor types prompted evaluation of its role in NETs, available data thus far show only limited antitumor activity in patients with low-grade neuroendocrine neoplasms; however, greater activity has been observed in higher grade neuroendocrine carcinomas.
We are pleased to present the highlights of these topics and more!
Michael Morse, MD
Professor of Medicine
Duke University Medical Center