LBA45 Randomized open label phase III study comparing the efficacy and safety of everolimus followed by chemotherapy (CT) with streptozotocin (STZ)-5FU upon progression or the reverse sequence, in advanced progressive panNETs: The SEQTOR study (GETNE 1206)

Salazar, Ramón; Tafuto, S.; Krogh, Merete; Teulé, Àlex; Garcia-Carbonero, R.; Klümpen, Heinz Josef; Cremer, Birgit; Sevilla, Isabel; Eriksson, Bengt O.; Tabaksblat, Elizaveta Mitkina; Metges, J-P.; Reed, Nick; Schrader, Joerg; Navarro, Valentı́; Valentí, V.; Hernando, Jorge; Colao, A.M.; Vestermark, L. W.; Carnaghi, Carlo; Capdevila, Joaquim Capdevila i

doi:10.1016/j.annonc.2022.08.044

Cited by 15 publications

(12 citation statements)

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“…The Phase III SEQTOR (GETNE 1206) trial, comparing the efficacy of everolimus followed by chemotherapy with the reverse sequence, also failed to detect difference in PFS with the first assigned treatment (PFS1). 27,28 There are also some limitations to the present study. First, it is a retrospective analysis with certain biases, and so large prospective trials are needed to provide more definitive evidence.…”

Section: Discussionmentioning

confidence: 88%

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Patients with non‐functional metastatic G2 pancreatic neuroendocrine tumor benefit from palliative surgery: A 20‐year single‐center retrospective analysis

You

Tang

et al. 2022

J Neuroendocrinology

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Pancreatic neuroendocrine tumor (pNET) is the most common subset (31.5%) of gastroenteropancreatic neuroendocrine tumor in China. Based on real‐world data from a single center, the present study aimed to evaluate the influence of clinical characteristics, medical treatment and surgery on the survival of non‐functional metastatic G2 pNET. In total, 114 metastatic non‐functional G2 pNET patients, who were treated and followed up in the Department of Medical Oncology, Peking Union Medical College Hospital (PUMCH) from 2001 until 2019, were analyzed retrospectively. The primary endpoint, overall survival (OS), was calculated from the date of diagnosis to the date of death. The second endpoint, progression‐free survival (PFS), was calculated from the date of diagnosis to the date of disease progression. Statistical data were analyzed to evaluate the effects of a clinical characteristic, medical treatment and surgery on OS and PFS. Sixty‐nine (60.5%) patients were male and 87 (76.3%) were aged < 60 years. The liver was the most common metastatic organ, with a total of 84 cases (73.7%). With respect to surgery, 32 (28.1%) patients underwent radical surgery and 37 (32.5%) underwent palliative surgery. Survival analysis showed that the 5‐year and 10‐year survival rates were 79.36% and 70.0%, respectively. Univariate and multivariate Cox regression analyses suggested that both radical (p < .001/.003) and palliative surgery (p < .001/.002) significantly prolonged OS, as revealed by the Kaplan–Meier test (p < .001). Subgroup analysis showed that palliative resection also significantly improves the prognosis in patients with multiple liver metastases. However, the first‐line systemic anti‐tumor therapy option showed no statistical differences in the present study. Overall, patients with non‐functional metastatic G2 pNET receiving palliative or radical surgery demonstrated significantly better survival. Prospective clinical trials are suggested to validate our findings.

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Section: Discussionmentioning

confidence: 88%

“…Currently, there are no data to guide sequencing of the systemic therapy options. The Phase III SEQTOR (GETNE 1206) trial, comparing the efficacy of everolimus followed by chemotherapy with the reverse sequence, also failed to detect difference in PFS with the first assigned treatment (PFS1) 27,28 …”

Section: Discussionmentioning

confidence: 99%

Patients with non‐functional metastatic G2 pancreatic neuroendocrine tumor benefit from palliative surgery: A 20‐year single‐center retrospective analysis

You

Tang

et al. 2022

J Neuroendocrinology

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“…It was the initial primary-end-point of the Seqtor study [time to treatment failure by adding PFS1 + PFS2 + time between both treatments (chemotherapy and everolimus)], but the study aim was changed to a direct comparison in first-line (PFS1 after chemotherapy or everolimus). 35 Hence, the impact of a prior treatment on the efficacy of a subsequent one is unknown, so is the risk of selecting a more aggressive NET under therapeutic pressure.…”

Section: The Sequence Optionsmentioning

confidence: 99%

“…- Doublet chemotherapy (5FU-Streptozotocin) was associated with similar PFS as everolimus in pNET, but the ORR was higher using chemotherapy. 35 …”

Section: The Sequence Optionsmentioning

confidence: 99%

“… 25 For patients in whom an objective response is not needed, a targeted therapy could be a first-line treatment option (as shown with everolimus in the Seqtor study). 35 In second-line, either after SSA or chemotherapy, everolimus and sunitinib are recommended in progressive G1-2 pNET, 10 , 12 while belzutifan is the treatment of choice for patients with advanced VHL-related pNET. 33 Since the presentation of the first results of the Oclurandom study, 38 patients with SSTR-positive pNET can be treated with PRRT before the administration of targeted therapies ( Table 2 and Figure 2(b) ).…”

Section: Proposition Of Therapeutic Sequencesmentioning

confidence: 99%

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

2023

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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.

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Update in the management of gastroenteropancreatic neuroendocrine tumors

Sedlack,

Varghese,

Naimian

et al. 2024

Cancer

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Neuroendocrine neoplasms are a diverse group of neoplasms that can occur in various areas throughout the body. Well‐differentiated neuroendocrine tumors (NETs) most often arise in the gastrointestinal tract, termed gastroenteropancreatic neuroendocrine tumors (GEP‐NETs). Although GEP‐NETs are still uncommon, their incidence and prevalence have been steadily increasing over the past decades. The primary treatment for GEP‐NETs is surgery, which offers the best chance for a cure. However, because GEP‐NETs are often slow‐growing and do not cause symptoms until they have spread widely, curative surgery is not always an option. Significant advances have been made in systemic and locoregional treatment options in recent years, including peptide‐receptor radionuclide therapy with α and β emitters, somatostatin analogs, chemotherapy, and targeted molecular therapies.

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LBA45 Randomized open label phase III study comparing the efficacy and safety of everolimus followed by chemotherapy (CT) with streptozotocin (STZ)-5FU upon progression or the reverse sequence, in advanced progressive panNETs: The SEQTOR study (GETNE 1206)

Cited by 15 publications

References 0 publications

Patients with non‐functional metastatic G2 pancreatic neuroendocrine tumor benefit from palliative surgery: A 20‐year single‐center retrospective analysis

Patients with non‐functional metastatic G2 pancreatic neuroendocrine tumor benefit from palliative surgery: A 20‐year single‐center retrospective analysis

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

Update in the management of gastroenteropancreatic neuroendocrine tumors

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