Efficacy and safety of first-line treatments for patients with advanced anaplastic lymphoma kinase mutated, non–small cell cancer: A systematic review and network meta-analysis
A partir d'une revue systématique de la littérature (9 études incluant au total 2 441 patients), cette méta-analyse en réseau compare l'efficacité et la toxicité de sept traitements de première ligne pour les cancers du poumon non à petites cellules avec mutation de la kinase ALK
Background : This study compares the safety and efficacy of first-line treatments for anaplastic lymphoma kinase (ALK)-mutated non–small cell lung cancer (NSCLC). Methods : A comprehensive literature search was conducted in PubMed, Embase, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov databases. Abstracts related to lung cancer presented at important international conferences were also reviewed. Randomized clinical trials that qualified the inclusion criteria were subjected to Bayesian network meta-analysis and systematically reviewed. Results : The authors included a total of nine studies including 2441 patients and seven first-line treatments (ensartinib, brigatinib, crizotinib, lorlatinib, alectinib, ceritinib, and pemetrexed-based chemotherapy). Overall, lorlatinib appeared to confer the best progression-free survival (PFS) (probability of being the best [Prbest], 90%; surface under the cumulative ranking curve [SUCRA], 98%), and the same conclusion was obtained on paired comparisons (lorlatinib vs. ceritinib [hazard ratio (HR), 0.31; 95% confidence interval (CI), 0.20–0.47); lorlatinib vs. chemotherapy [HR, 0.17; 95% CI, 0.12–0.23]; crizotinib vs. lorlatinib [HR, 3.6; 95% CI, 2.4–5.2]; and brigatinib vs. lorlatinib [HR, 1.7; 95% CI, 1.0–2.8]). Alectinib conferred the best overall survival (OS) and safety profile. In the Asian population, ensartinib conferred the best PFS (Prbest 50%, SUCRA 87%), and for patients with brain metastases at baseline, lorlatinib showed the best PFS (Prbest 70%, SUCRA 93%). Conclusions : For first-line treatment of patients with ALK-positive NSCLC, lorlatinib was associated with the best PFS and objective response rate, but poorer safety profile, whereas alectinib demonstrated the best OS and safety profile. In Asians, ensartinib conferred the best PFS benefit, and in the brain baseline metastasis population, lorlatinib conferred the best PFS benefit.