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Therapeutic sequences in patients with grade 1−2 neuroendocrine tumors (NET): an observational multicenter study from the ELIOS group

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Abstract

Purpose

Many different treatments are suggested by guidelines to treat grade 1−2 (G1−G2) neuroendocrine tumors (NET). However, a precise therapeutic algorithm has not yet been established. This study aims at identifying and comparing the main therapeutic sequences in G1−G2 NET.

Methods

A retrospective observational Italian multicenter study was designed to collect data on therapeutic sequences in NET. Median progression-free survival (PFS) was compared between therapeutic sequences, as well as the number and grade of side effects and the rate of dose reduction/treatment discontinuation.

Results

Among 1182 patients with neuroendocrine neoplasia included in the ELIOS database, 131 G1–G2 gastroenteropancreatic, lung and unknown primary NET, unresectable or persistent/relapsing after surgery, treated with ≥2 systemic treatments, were included. Four main therapeutic sequences were identified in 99 patients: (A) somatostatin analogs (SSA) standard dose to SSA high dose (n = 36), (B) SSA to everolimus (n = 31), (C) SSA to chemotherapy (n = 17), (D) SSA to peptide receptor radionuclide therapy (PRRT) (n = 15). Median PFS of the second-line treatment was not reached in sequence A, 33 months in sequence B, 20 months in sequence C, 30 months in sequence D (p = 0.16). Both total number and severity of side effects were significantly higher in sequences B and C than A and D (p = 0.04), as well as the rate of dose reduction/discontinuation (p = 0.03).

Conclusions

SSA followed by SSA high dose, everolimus, chemotherapy or PRRT represent the main therapeutic sequences in G1−G2 NET. Median PFS was not significantly different between sequences. However, the sequences with SSA high dose or PRRT seem to be better tolerated than sequences with everolimus or chemotherapy.

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Acknowledgements

Thanks to all the participants to the ELIOS (Educational Learning Investigational Observational Study) Multicentre Study for their support.

Author information

Authors and Affiliations

  1. Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy

    Antongiulio Faggiano

  2. Division of Endocrinology, Department of Clinical Medicine and Surgery, Federico II University of Naples, Naples, Italy

    Silvana Di Maio, Roberta Modica & Annamaria Colao

  3. Oncology Unit, Azienda Ospedaliera Antonio Cardarelli, Naples, Italy

    Carmela Mocerino & Ferdinando Riccardi

  4. Oncology Unit, Department of Clinical Medicine and Surgery, Federico II University of Naples, Naples, Italy

    Margaret Ottaviano & Giovannella Palmieri

  5. Medical Oncology Unit, Istituto Nazionale per lo studio e la cura dei tumori “Fondazione G. Pascale”-IRCCS, Naples, Italy

    Chiara De Divitiis & Salvatore Tafuto

  6. Division of Endocrinology, Diabetology and Metabolism, DIBIMIS, University of Palermo, Palermo, Italy

    Valentina Guarnotta

  7. Department of Public Health, Federico II University of Naples, Naples, Italy

    Pasquale Dolce

  8. Oncology Unit, Department of Medical Oncology, IOM—Istituto Oncologico del Mediterraneo, Catania, Italy

    Ivana Puliafito

  9. Fondazione IRCCS Casa Sollievo della Sofferenza, UO di Oncologia, San Giovanni Rotondo, FG, Italy

    Lucia Tozzi

  10. Oncology Unit, AO dei Colli, Monaldi Unit, Naples, Italy

    Antonella Di Sarno & Antonella Bianco

  11. Oncology Unit, Ospedale Civico, Lecce, Italy

    Silvana Leo

  12. Division of Oncology, Department of Surgical and Oncological Sciences, University of Palermo, Palermo, Italy

    Giuseppe Badalamenti

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  1. Antongiulio Faggiano
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Correspondence to Antongiulio Faggiano.

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The authors declare that they have no conflict of interest.

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The study was conducted in accordance with the 1964 Declaration of Helsinki and approved by the ethics committee of each institution. All patients gave written informed consent.

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Faggiano, A., Di Maio, S., Mocerino, C. et al. Therapeutic sequences in patients with grade 1−2 neuroendocrine tumors (NET): an observational multicenter study from the ELIOS group. Endocrine 66, 417–424 (2019). https://doi.org/10.1007/s12020-019-01894-0

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