Mini-oral session NETs

Dr Willem Lybaert, medical oncologist at the VITAZ hospital in Sint Niklaas and the University hospital Antwerp summarizes the key take-aways from the mini-oral session on neuroendocrine tumours at ESMO 2024.

In a first of two studies in patients with thyroid cancer (REGOMUNE), the combination of regorafenib and avelumab proved to be associated with an overall response rate (ORR) of 58.4% and a median progression-free survival (PFS) of 12.6 months in a cohort of 50 patients with radioiodine-refractory differentiated thyroid cancer (RR-DTC). Interestingly, the PFS with this combination proved to be longer in multikinase inhibitor (MKI) pretreated patients in whom a median PFS of 20.4 months was reported. The treatment was relatively well-tolerated without any treatment-related deaths.1 Also in RR-DTC, real world data provided reassuring data for the use of lenvatinib in this setting. This study, including 337 patients, revealed a 3-year real-world PFS and OS rate of 53.4% and 77.1%, respectively. In addition, 74.8% obtained a response to the therapy. The toxicity was in line with previous reports with this agent.2

Subsequently, three phase II studies illustrated the renewed interest for anti-angiogenesis in patients with advanced NET. In the CVM-005 study (N=35), the TRAP1 inhibitor CVM-1118 proved to be associated with a median PFS and OS of 10.5 and 22.4 months, respectively. Interestingly, the median PFS was markedly longer in patients with an extrahepatic NET than in patients with a pancreatic NET (22.4 vs. 8.9 months). Furthermore, the addition of a somatostatin analogue to the treatment substantially boosted the PFS (median ~22 months). The treatment was well-tolerated without any serious TRAEs and a low discontinuation rate.3 An interim analysis of the phase II CABONEN study, evaluating cabozantinib in 34 patients with advanced, low-proliferative, grade 3 neuroendocrine neoplasms (NET and NEC) indicated a promising median PFS of 6.7 months with a proportion of patients having long-lasting responses. The toxicity of the treatment was in line with the known safety profile of cabozantinib.4 Finally, the phase RamuNET-study evaluated the combination of dacarbazine and ramucirumab in patients with progressive, well-differentiated metastatic pancreatic NET. After 6 months of therapy, an ORR of 18.8% was reported with disease control in 71.1% of patients and a preliminary median PFS of 12.2 months. The treatment proved to be tolerable, with only 12.6% of grade ≥3 adverse events.5

In addition to this, the mini-oral session featured a post-hoc, multivariate efficacy analysis of the pivotal phase III NETTER-2 study which evaluated 177Lu-DOTATE in patients with advanced, grade 2-3, somatostatin-receptor (SSTR)-positive gastroenteropancreatic (GEP)-NET. The presented analysis confirmed the efficacy of this treatment modality across all investigated subgroups, with a more pronounced PFS benefit in patients with a NET originating in the small intestine, in patients with a lower chromogranin A level, in patients with a lower Ki67 score and in patients with a higher SSTR uptake score.6

A final presentation of the session underscored the importance of carcinoid heart disease (CHD) in patients with NETs and carcinoid syndrome. In a cohort of patients with stage IV small-intestine NETs and carcinoid syndrome, about a quarter (24.8%) of patients was shown to have CHD, a feature that was associated with a dismal OS prospect (median OS for patients with and without CHD reported at 4.5 and 8.9 years, respectively). The investigators therefore underscored the need to routinely measure the level of urine 5-HIAA and NT-proBNP and to perform an echocardiogram in NET patients with carcinoid syndrome.7