A practical proposal on treatment sequencing of metastatic well-differentiated neuroendocrine tumours

According to the neuroendocrine tumour (NET) characteristics, 3 to 7 different treatment options are available, corresponding to 6 to 5,040 theoretical different sequences. Even though each patient is unique and despite a large heterogeneity in NET characteristics, the present review aims to discuss the main sequences and addresses how one can propose the best sequence to treat metastatic NET (mNET) on a case-by-case basis. Each treatment must be discussed during dedicated multi-disciplinary meetings, and inclusions in clinical trials should be favoured. After a thorough characterization of patients and their mNET, and taking into account the availability of drugs, the first-line treatment should be chosen according to the treatment aim. The latter is determined based on three main topics (efficacy, safety, and patient preferences) that do not necessarily converge and must be defined a priori. At baseline, physicians should design an a priori full therapeutic sequence, which may evolve at each step depending on the response to previous treatment, the occurrence of chronic toxicities, and the patients' perception of the prior treatment. To improve knowledge in terms of effectiveness and risk of cumulative toxicities regarding the different sequences, real-world data using long follow-up durations are necessary; such issues will not be resolved by randomized clinical trials.

Automated summary

According to the characteristics of neuroendocrine tumors (NET), there are 3 to 7 different treatment options, corresponding to 6 to 5,040 theoretical different sequences. Despite heterogeneity in NET characteristics, this review discusses main sequences and proposes a case-by-case basis for treating metastatic NET (mNET). Each treatment should be discussed in multi-disciplinary meetings, and clinical trials should be favored. The first-line treatment should be chosen based on treatment aim, taking into account efficacy, safety, and patient preferences. Real-world data using long follow-up durations are necessary to improve knowledge regarding effectiveness and risk of cumulative toxicities for different sequences.