OBJECTIVES:

This study aimed to assess the efficacy of TKIs used for the first line (1L) treatments of advanced or metastatic ALK-positive NSCLC along with the subgroup analysis for brain metastasis (BM).

METHODS:

A Bayesian network meta-analysis (NMA) identifying published randomized-controlled trials (RCTs) reporting progression-free survival (PFS) or overall survival (OS) was conducted. We searched the PUBMED, PMC, Embase, MEDLINE, Web of Science, WILEY, Cochrane Library, Clinical Trials, CNKI, Wanfang Data, Chongqing VIP Data and main database of ESMO, ASCO and CSCO. Searches were from the construction day to June 15th, 2022. Random-effects model was chosen with MCMC method run by 40,000 iterations. Rankogram using surface under the cumulative ranking curve (SUCRA) was reported.

RESULTS:

A total of 11 RCTs investigating 7 medications were included. For PFS of all patients, the top-ranking medications compared to chemotherapy sorted by SUCRA were Lorlatinib (HR: 0.13, 95% CrI: 0.086-0.19), Alectinib (HR: 0.17, 95% CrI: 0.13-0.22), Brigatinib (HR: 0.23, 95% CrI: 0.16-0.33), Ensartinib (HR: 0.24, 95% CrI: 0.16-0.36), Crizotinib (HR: 0.47, 95% CrI: 0.41-0.55), Ceritinib (HR: 0.49, 95% CrI: 0.37-0.66), chemotherapy. For OS of all patients, the results were Alectinib (HR: 0.48, 95% CrI: 0.32-0.72), Lorlatinib (HR: 0.60, 95% CrI: 0.33-1.10), Brigatinib (HR: 0.67, 95% CrI: 0.42-1.10), Ensartinib (HR: 0.75, 95% CrI: 0.43-1.30), Crizotinib (HR: 0.83, 95% CrI: 0.68-1.00), Ceritinib (HR: 1.00, 95% CrI: 0.67-1.50), chemotherapy.

For PFS of BM subgroup, the results were Lorlatinib (HR: 0.11, 95% CrI: 0.0064-2.00), Alectinib (HR: 0.13, 95% CrI: 0.0012-1.20), Brigatinib (HR: 0.16, 95% CrI: 0.0090-2.70), Ensartinib (HR: 0.30, 95% CrI: 0.017-5.10), Crizotinib (HR: 0.54, 95% CrI: 0.10-2.70), Ceritinib (HR: 0.54, 95% CrI: 0.057-5.30), chemotherapy.

CONCLUSIONS:

Lorlatinib showed better estimates of efficacy in comparison to the first and second generation TKIs especially in PFS, with its ranking by the front, which can be considered as the best option for clinical treatment.