Q-TWiST analysis of survival benefits with brigatinib versus crizotinib in patients with anaplastic lymphoma kinase-positive non-small cell lung cancer based on results of the ALTA-1L trial
Menée à partir de données portant sur 275 adultes atteints d'un cancer du poumon non à petites cellules ALK+ de stade localement avancé ou métastatique et inclus dans un essai de phase III, cette étude compare l'intérêt, du point de vue de la survie ajustée sur la qualité de vie (durée sans symptômes liés à la maladie ou sans toxicité des traitements), du brigatinib et du crizotinib en traitement de première ligne
Objectives: The ALTA-1L phase 3 open-label trial demonstrated increased progression-free survival (PFS) with brigatinib versus crizotinib in patients with anaplastic lymphoma kinase-positive (ALK-positive) locally advanced or metastatic non-small cell lung cancer (NSCLC) previously untreated with ALK-targeted therapy. This post-hoc analysis of data from the ALTA-1L trial used the quality-adjusted (QA) time without symptoms of disease or toxicity (Q-TWiST) methodology to compare the QA survival benefit of brigatinib versus crizotinib in this patient population. Patients and Methods: The Q-TWiST analysis was performed using final (January 29, 2021) individual patient-level blinded independent review committee (BIRC)- and investigator-assessed survival data for brigatinib (n=137) and crizotinib (n=138) in adult patients (N=275) with ALK-positive locally advanced or metastatic NSCLC previously untreated with ALK-targeted therapy. Q-TWiST was compared between the two treatments. Subgroup analyses were performed in patients stratified by various clinicopathological characteristics, including presence or absence of brain metastases at baseline. Results: Brigatinib was associated with significantly longer time without symptoms of disease or toxicity (P<0.001) than crizotinib, with significantly greater Q-TWiST (mean [SE] months: BIRC-assessed, 28.24 [1.15] versus 25.11 [1.07], P=0.045; investigator-assessed, 28.46 [1.16] versus 24.76 [1.06], P=0.018). Relative gains in Q-TWiST with brigatinib compared to crizotinib were clinically meaningful (BIRC-assessed, 10.4%; investigator-assessed, 12.3%). Patients with brain metastases at baseline receiving brigatinib had significantly greater Q-TWiST (mean [SE] months: BIRC-assessed, 28.96 [1.90] versus 18.95 [1.86], P=0.0001) than those receiving crizotinib. Conclusion: First-line brigatinib treatment was associated with significant and clinically meaningful gains in Q-TWiST compared to crizotinib in patients with ALK-positive locally advanced or metastatic NSCLC, supporting the results of the ALTA-1L trial and brigatinib as a safe and effective first-line treatment for ALK-positive NSCLC.