Alectinib for the treatment of pretreated RET-rearranged advanced NSCLC: Results of the ETOP ALERT-lung trial

Enriqueta Felip, Egbert F Smit, Miguel A Molina-Vila, Urania Dafni, Bartomeu Massuti, Thierry Berghmans, Filippo de Marinis, Francesco Passiglia, Anne-Marie C Dingemans, Manuel Cobo, Santiago Viteri, Christian Britschgi, Sinead Cuffe, Mariano Provencio, Sabine Merkelbach-Bruse, Charitini Andriakopoulou, Roswitha Kammler, Barbara Ruepp, Heidi Roschitzki-Voser, Solange PetersJürgen Wolf, Rolf Stahel*, ETOP 12-17 ALERT-lung Collaborators

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


BACKGROUND: Alectinib, a highly selective next generation ALK-inhibitor, has exhibited potent anti-tumour activity in RET-rearranged NSCLC in the preclinical stage.

METHODS: ALERT-lung is a single-arm, phase II trial evaluating the activity of alectinib for the treatment of pretreated RET-rearranged advanced NSCLC. Alectinib was administered orally, 600 mg, twice per day until progression, refusal or unacceptable toxicity (treatment could continue beyond progression, if patient was deriving clinical benefit). Patient recruitment closed prematurely due to discouraging results for alectinib in a phase I/II study in the same indication.

RESULTS: All 14 patients who enrolled until the premature accrual closure, received at lease one dose of alectinib. Among them, median age was 61 years, majority (71 %) was female, never smokers, of ECOG PS 1. No objective response (complete or partial response) was recorded. Of the 13 evaluable patients, three (23 %) achieved and maintained disease stabilisation for 24 weeks. Up to 31 March 2021 (median follow-up 15.9 months), 12 PFS-events (92 %) were observed, with median PFS of 3.7 months (95 % C.I.: 1.8 - 7.3 months). Overall, three deaths (23 %) were reported. Seven patients (50 %) experienced grade ≥ 3 adverse events, while three discontinued treatment due to erythema multiforme of grade 3, related to alectinib. No treatment-related serious adverse event was reported.

CONCLUSIONS: Accrual into our trial was terminated early in response to other reports of limited activity of alectinib in patients with RET-fusion NSCLC and the emergence of more potent selective RET-inhibitors. Also in our trial, alectinib did not show the expected potential for anti-tumour activity in NSCLC.

Original languageEnglish
Pages (from-to)94-99
Number of pages6
JournalLung Cancer
Early online date12 Aug 2022
Publication statusPublished - Oct 2022


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