A comprehensive evaluation of ALK inhibitors in the first-line treatment of patients with ALK-positive non-small cell lung cancer

Abstract

There are currently six ALK inhibitors available for the first-line treatment of patients diagnosed with ALK-positive advanced non-small cell lung cancer (NSCLC). However, clinicians face challenges in selecting the most appropriate drug for treatment. We have collated pertinent evaluative evidence and undertaken a multifaceted assessment of the enrolled medications across five critical dimensions: safety, efficacy, pharmaceutical properties, drug economy, and other properties. This comprehensive analysis aims to furnish a robust foundation for the selection and clinical deployment of pharmaceuticals, thereby advocating for the judicious and rational utilization of medications in clinical practice. Upon conducting an exhaustive evaluation, we determined that the aggregate scores for all ALK inhibitors under review surpassed the threshold of 75 points, with brigatinib distinguishing itself as the top performer in terms of overall scoring. Considering that safety, efficacy, and pharmacological properties are paramount in the comprehensive clinical appraisal of pharmaceuticals, lorlatinib emerged with the highest score when evaluated solely on these three critical criteria. Through an extensive evaluation of ALK inhibitors, it has been determined that each ALK inhibitor possesses unique strengths across a spectrum of five distinct dimensions. Notably, when evaluating both the comprehensive scores across all five dimensions and the focused scores for the top three dimensions, third-generation inhibitors consistently ranked as the optimal choice. Healthcare organizations can leverage these findings to assess and select ALK inhibitors that align with their specific requirements, utilizing the comparative rankings and scores across various dimensions to inform their selection process.

Keywords

ALK inhibitors / Non-small cell lung cancer / Comprehensive evaluation / Clinical rational drug use

Declarations

Not applicable.

Authors' contributions

Y. Zhang: Software, investigation, formal analysis, and data curation. Y. Hong: Validation and investigation. Y. Rao: Writing - review and editing, validation, supervision, project administration, methodology, and conceptualization. Z. Ye: Writing - original draft, investigation, funding acquisition, data curation, and conceptualization. Y. Zhou: Investigation, formal analysis, and data curation. L. Liu: Investigation, formal analysis, and data curation.

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Availability of data and materials

Not applicable.

Funding

This research was supported by the Fund of Zhejiang Pharmaceutical Association (2022ZYYL01).

Declaration of Competing Interest

The authors declare that they have no competing interests.

Acknowledgements

Not applicable.

Authors’ other information

Not applicable.

References

[1] Addeo A, Tabbo F, Robinson T, et al. Precision medicine in ALK rearranged NSCLC: a rapidly evolving scenario. Crit Rev Oncol Hematol. 2018; 122:150-156.

[2] Bayliss R, Choi J, Fennell DA, et al. Molecular mechanisms that underpin EML4-ALK driven cancers and their response to targeted drugs. Cell Mol Life Sci. 2016; 73(6):1209-1224.

[3] Peng L, Zhu L, Sun Y, et al. Targeting ALK Rearrangements in NSCLC: current State of the Art. Front Oncol. 2022; 12:863461.

[4] Wang WQ, Xu T, Zhang JJ, et al. A comprehensive clinical evaluation of first-line drugs for ALK-positive advanced non-small cell lung cancer. J Thorac Dis. 2023; 15(4):1935-1947.

[5] Zhao Z, Dong Z, Liu J. A quick guideline for drug evaluation and selection in chinese medical Institutions (the Second Edition). Her Med. 2023; 42(4):447-456.

[6] Solomon BJ, Mok T, Kim DW, et al. First-line crizotinib versus chemotherapy in ALK-positive lung cancer. N Engl J Med. 2014; 371(23):2167-2177.

[7] Soria JC, Tan DSW, Chiari R, et al. First-line ceritinib versus platinum-based chemotherapy in advanced ALK-rearranged non-small-cell lung cancer (ASCEND-4): a randomised, open-label, phase 3 study. Lancet. 2017; 389(10072):917-929.

[8] Hida T, Nokihara H, Kondo M, et al. Alectinib versus crizotinib in patients with ALK-positive non-small-cell lung cancer (J-ALEX): an open-label, randomised phase 3 trial. Lancet. 2017; 390(10089):29-39.

[9] Horn L, Wang Z, Wu G, et al. Ensartinib vs crizotinib for patients with anaplastic lymphoma kinase-positive non-small cell lung cancer: a randomized clinical trial. JAMA Oncol. 2021; 7(11):1617-1625.

[10] Camidge DR, Kim HR, Ahn MJ, et al. Brigatinib versus crizotinib in advanced ALK inhibitor-naive ALK-positive non-small cell lung cancer: second interim analysis of the phase III ALTA-1L trial. J Clin Oncol. 2020; 38(31):3592-3603.

[11] Shaw AT, Bauer TM, de Marinis F, et al. First-line lorlatinib or crizotinib in advanced ALK-positive lung cancer. N Engl J Med. 2020; 383(21):2018-2029.

[12] Ma HC, Liu YH, Ding KL, et al. Comparative efficacy and safety of first-line treatments for advanced non-small cell lung cancer with ALK-rearranged: a meta-analysis of clinical trials. BMC Cancer. 2021; 21(1):1278.

[13] Li X, Ding CY, Ren BN, et al. Digital selection and evaluation of state negotiates drugs of new GLP-1RA semaglutide injection. Chin J Mod Appl Pharm. 2022; 39(22):2981-2990.