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. 2024:41:100842.
doi: 10.1016/j.ctarc.2024.100842. Epub 2024 Sep 6.

The likelihood of being helped or harmed as a patient-centred tool to assess ALK-Inhibitors clinical impact and safety in ALK-addicted non-small cell lung cancer: A systematic review and sensitivity-analysis

Luca Mastrantoni  1 , Giulia Giordano  2 , Emanuele Vita  3 , Guido Horn  4 , Jacopo Russo  5 , Armando Orlandi  6 , Gennaro Daniele  7 , Diana Giannarelli  8 , Giampaolo Tortora  9 , Emilio Bria  10
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Free article

The likelihood of being helped or harmed as a patient-centred tool to assess ALK-Inhibitors clinical impact and safety in ALK-addicted non-small cell lung cancer: A systematic review and sensitivity-analysis

Luca Mastrantoni et al. Cancer Treat Res Commun. 2024.
Free article

Abstract

Background: In untreated ALK-positive non-small cell lung cancer no randomized controlled trials (RCTs) are available directly comparing next-generation ALK-inhibitors. We conducted a sensitivity analysis using the likelihood of being helped or harmed (LHH).

Methods: Phase III trials comparing ALK-inhibitors to crizotinib were included. Efficacy outcomes were progression-free survival (PFS), objective response rate (ORR), PFS in patients with brain metastases and intracranial ORR. Safety outcomes were grade 3-4 adverse events (AEs), dose reductions and discontinuations.

Results: Six RCTs (1524 patients) were included. Lorlatinib and brigatinib had the lowest NNT for intracranial outcomes. Alectinib demonstrated favourable LHHs for grade 3-4 AEs, dose reductions and discontinuations. Brigatinib LHHs were low for common AEs, mainly laboratory anomalies and hypertension. Ensartinib showed mainly skin toxicity. Lorlatinib LHHs were low for specific grade 3-4 AEs, mainly metabolic alterations.

Conclusions: The four ALK-inhibitors exhibited favourable risk-benefit ratios. Lorlatinib showed the lowest NNT for systemic efficacy and, alongside with Brigatinib, lower NNTs for intracranial efficacy. Alectinib exhibited higher LHHs for AEs.

Registration: PROSPERO registration number: CRD42023389101.

Keywords: ALK-inhibitors; Alectinib; Brigatinib; Ensartinib; LHH; Lorlatinib.

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Conflict of interest statement

Declaration of competing interest L.M., G.G., E.V, G.H., J.R. and G.D. declare no conflict of interest. A.O. has declared consulting fees/advisory role for Novartis, Roche, Eli-Lilly, Amgen, Daiichi Sankyo, travel and accommodation by Daiichi Sankyo, Novartis, Roche, Pfizer. D.G. received educational courses fee from MSD and Amgen. G.T. is supported by funds of Ministero della Salute (Ricerca Corrente 2022). E.B. is currently supported by the Associazione Italiana per la Ricerca sul Cancro (AIRC) under Investigator Grant (IG) No. IG20583. E.B. is supported by Institutional funds of Università Cattolica del Sacro Cuore (UCSC-project D1). E.B. is supported by funds of Ministero della Salute (Ricerca Corrente 2023). E.B. received speakers’ and travels’ fee from MSD, Astra-Zeneca, Pfizer, Eli-Lilly, BMS, Novartis and Roche. E.B. received institutional research grants from Astra-Zeneca, Roche.

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