TY - JOUR
T1 - Alectinib for the treatment of pretreated RET-rearranged advanced NSCLC
T2 - Results of the ETOP ALERT-lung trial
AU - Felip, Enriqueta
AU - Smit, Egbert F
AU - Molina-Vila, Miguel A
AU - Dafni, Urania
AU - Massuti, Bartomeu
AU - Berghmans, Thierry
AU - de Marinis, Filippo
AU - Passiglia, Francesco
AU - Dingemans, Anne-Marie C
AU - Cobo, Manuel
AU - Viteri, Santiago
AU - Britschgi, Christian
AU - Cuffe, Sinead
AU - Provencio, Mariano
AU - Merkelbach-Bruse, Sabine
AU - Andriakopoulou, Charitini
AU - Kammler, Roswitha
AU - Ruepp, Barbara
AU - Roschitzki-Voser, Heidi
AU - Peters, Solange
AU - Wolf, Jürgen
AU - Stahel, Rolf
AU - ETOP 12-17 ALERT-lung Collaborators
N1 - Copyright © 2022 Elsevier B.V. All rights reserved.
PY - 2022/10
Y1 - 2022/10
N2 - 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.
AB - 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.
U2 - 10.1016/j.lungcan.2022.08.008
DO - 10.1016/j.lungcan.2022.08.008
M3 - Article
C2 - 36030612
SN - 0169-5002
VL - 172
SP - 94
EP - 99
JO - Lung Cancer
JF - Lung Cancer
ER -