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

Abstract 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. Plain Language Summary Among the many molecularly targeted drugs currently used to treat anaplastic lymphoma kinase mutation‐positive non–small cell lung cancer, lorlatinib may be one of the most effective targeted drugs. Lung cancer has long been at the top of cancer rankings in terms of incidence and mortality. Today, the treatment of lung cancer has moved into the era of precision therapy. In this article, we use a statistical approach to compare the efficacy and safety of targeted drugs that have been used in the first‐line treatment of anaplastic lymphoma kinase mutations to improve the reference for clinicians to make treatment decisions in the real world.