To date no therapy can be considered as a standard of care for patients with an advanced lung NET. Everolimus is the only drug specifically approved for lung NETs, although this approval was based on the positive results of a large-randomised phase III trials including a mixed population of GI and lung NETs and it regarded just the nonfunctioning NETs. SSAs are recommended for functioning lung NETs but they are allowed to be proposed also for non-functioning lung NETs despite they were approved as antiproliferative agents just for GEP NETs. PRRT is investigational for lung NETs whereas it was approved for all GEP NETs. In many Countries temozolomide or other chemotherapeutic agents are allowed to be proposed for lung NETs even without specific evidence and approval. Liver-directed treatments, surgical and not surgical, are usually discussed as in GEP setting, outside specific evidence.

So far no specific sequence or integration of therapies have been validated for advanced lung NETs.

On this basis in clinical practice EVE, the only specifically approved drug for lung NETs, should be managed among this heterogeneous therapeutic landscape. Therefore, it is advisable that each clinical case is discussed within a NET-dedicated multidisciplinary team (MDT) and a therapeutic strategy rather than a single therapy choice is shared. Evidence, guidelines, goals of treatment are all critical factors to be considered to make an adequate clinical decision.

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There is evidence to consider EVE as first-line or further-line therapy in nonfunctioning progressive advanced lung NETs. Although there is not evidence against the use of EVE in naïve patients with lung NET however data are more solid for pre-treated patients, mainly with SSA.

Clinical data about a combination of EVE + SSA in non-functioning lung NETs are poor and not solid.

Despite the negative statistical results but apparently positive clinical impact of the RADIANT-2 trial EVE + SSA could be considered in selected cases of advanced functioning lung NETs resistant to SSA, provided that it is allowed by local regulatory authorities.


We thank Mr William Russell-Edu for supporting us for the design and the conduction of the comprehensive literature search.


Dr Nicola Fazio reports personal fees and research funds to the institution from Novartis, AAA and Ipsen, and personal fees from Pfizer. The authors report no other conflicts of interest in this work.

Marta Peri,1 Nicola Fazio2

1Medical Oncology, Department of Surgical, Oncological and Stomatological Sciences, University of Palermo, Palermo, Italy; 2Division of Gastrointestinal Medical Oncology and Neuroendocrine Tumors, European Institute of Oncology, IEO, IRCCS, Milan, Italy
Correspondence: Nicola Fazio via Ripamonti 435, Milan 20141, Italy

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Source: Lung Cancer: Targets and Therapy.
Originally published July 8, 2020.

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