Gastrointestinal Cancers
Theranostics: recent developments in neuroendocrine tumors
RYZ101 (225Ac-DOTATATE) is a first-in-class alpha-emitting radiopharmaceutical being developed for somatostatin receptor-2-expressing (SSTR2+) solid tumors. The ongoing phase 1b/3 ACTION-1 trial (NCT05477576) is currently comparing RYZ101 with standard therapy in patients with well-differentiated gastroenteropancreatic neuroendocrine tumors (GEP-NETs) who have progressed after 177Lu-labelled somatostatin analogue (SSA) therapy.
Recent progress in the treatment of neuroendocrine tumors
Capecitabine plus temozolomide (CAPTEM) is widely used for the treatment of advanced, unresectable, and progressive neuroendocrine tumors (NETs). However, data are limited regarding its association with radioligand therapy (RLT)/peptide receptor radionuclide therapy (PRRT).
New developments in the diagnosis of neuroendocrine tumors
Neuroendocrine neoplasms (NENs) comprise a rare group of heterogenous neoplasms that originate from cells with a neuroendocrine phenotype and can arise in almost every organ or region of the body [1]. They display a variable biological behavior; in fact, in some patients the disease may be stable for years, whereas in others, it might be very aggressive [2].
Emerging therapies in solid tumors
Interleukin-8 (IL-8), also known as chemokine (C-X-C motif) ligand 8, is a pro-inflammatory chemokine that exerts direct pro-tumorigenic effects primarily by recruiting immunosuppressive cells into the tumor microenvironment such as neutrophils and myeloid-derived suppressor cells. IL-8 has also been shown to promote cancer progression and resistance to therapy, by inducing angiogenesis, epithelial-mesenchymal transition (EMT), and cancer stem cell (CSC) self-renewal.
Biomarkers: predicting response to treatment
pNETs frequently contain mutations in MEN1, ATRX, DAXX, and the PI3K/AKT/mTOR pathway. However, more data are needed to determine whether this information can predict response to standard treatments, such as CAPTEM. At NANETS 2022, Hendifar et al. presented retrospective data on 25 patients with well-differentiated grade 1 and 2 pNETs who had received CAPTEM as first- or second-line treatment and whose tumors had been molecularly characterized through next-generation sequencing (NGS).
Advances in immunotherapy for neuroendocrine tumors
Chemotherapy is currently the SoC first-line treatment for high-grade neuroendocrine neoplasms (HG-NENs), even though it only provides modest benefits in OS and PFS. Given the lack of therapeutic options for metastatic NEN patients and the promising antitumor activity of immunotherapy demonstrated across several solid cancer types, the efficacy of pembrolizumab monotherapy was investigated in an open-label, nonrandomized phase II study in patients with metastatic extra-pulmonary HG-NEN (Ki67 >20 %).
SSTR-positive neuroendocrine tumors: peptide receptor radionuclide therapy
177Lu-DOTATATE was approved by the FDA in 2018 following the encouraging results from the NETTER-1 trial, where a regimen of 4 doses was shown to improve both progression-free survival (PFS) and overall survival (OS) compared to somatostatin analog (SSA) therapy in patients with advanced gastroenteropancreatic neuroendocrine tumors (GEP-NETs).
Recent progress in the treatment of neuroendocrine tumors
Five systemic therapeutic options are currently approved for advanced pancreatic neuroendocrine tumors (PanNET): Streptozotocine-based chemotherapy, everolimus, sunitinib, lanreotide, and PRRT with 177Lu-DOTA-octreotate (OCLU). For PRRT, data from retrospective studies have reported partial responses in advanced PanNET patients [1].
