Table Info

Table 1.

Analysis of the treatment ranking

Treatments	Outcomes of efficacy						Outcome of safety
	Rank OS	SUCRA	Rank PFS	SUCRA	Rank encephalic PFS	SUCRA	Rank AEs	SUCRA-AEs
Alectinib	1	88%	2	78%	4	59%	5	55%
Lorlatinib	2	67%	1	96%	1	98%	7	12%
Brigatinib	3	56%	4	55%	2	73%	6	24%
Alectinib 300	4	55%	3	77%	5	56%	1	99%
Ceritinib	5	50%	7	15%	6	21%	8	8%
Ensartinib	6	43%	5	51%	3	68%	4	57%
Crizotinib	7	29%	6	27%	6	21%	2	79%
Platinum-based chemotherapy	8	10%	8	0%	8	2%	3	64%
I²	-	39.6%	-	58.7%	-	73.7%	-	-

-: no data

Supplementary materials

The supplementary material for this article is available at: https://www.explorationpub.com/uploads/Article/file/1002187_sup_1.pdf.

Declarations

Author contributions

MF and PL: Conceptualization, Data curation, Writing—original draft. RF, RG, VA and GS: Writing—review & editing. DG and AC: Methodology. GD: Writing—review & editing, Supervision. All authors read and approved the submitted version.

Conflicts of interest

Raffaele Giusti declared financial interests with Roche (expert testimony, personal, advisory board for clinician’s expertise on drug management); Molteni (writing engagement, personal, publication fee for open access manuscript); Novartis (advisory board, personal); Angelini Pharma (invited speaker, personal, invited speaker to national and international congress); Pfizer (advisory board, personal) and Takeda (expert testimony, personal, expert testimony on drug management). Giovanni Scambia has served as consultant for TESARO Bio Italy S.r.l and Johnson & Johnson. He received onoraria from Clovis Oncology Italy S.r.l, and institutional research funding from MSD Italy S.r.l. Gennaro Daniele has served on advisory board of Beigene and received support for travel and accomodation from Roche. The other authors declare that they have no conflict of interest.

Ethical approval

Not applicable.

Consent to participate

Not applicable.

Consent to publication

Not applicable.

Availability of data and materials

Study data made available upon reasonable request to the first author (Marco Filetti, marco.filetti@policlinicogemelli.it).

Funding

Not applicable.

Copyright

References

Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71:209–49. [DOI] [PubMed]

American Lung Association [internet]. Washington: The Association; c2023 [cited 2022 Nov 16]. Available from: https://www.lung.org/

Travis WD, Brambilla E, Riely GJ. New pathologic classification of lung cancer: relevance for clinical practice and clinical trials. J Clin Oncol. 2013;31:992–1001. [DOI] [PubMed]

Friedlaender A, Banna G, Patel S, Addeo A. Diagnosis and treatment of ALK aberrations in metastatic NSCLC. Curr Treat Options Oncol. 2019;20:79. [DOI] [PubMed]

Malik SM, Maher VE, Bijwaard KE, Becker RL, Zhang L, Tang SW, et al. U.S. Food and Drug Administration approval: crizotinib for treatment of advanced or metastatic non-small cell lung cancer that is anaplastic lymphoma kinase positive. Clin Cancer Res. 2014;20:2029–34. [DOI] [PubMed]

Solomon BJ, Mok T, Kim DW, Wu YL, Nakagawa K, T Mekhail, et al.; PROFILE 1014 Investigators. First-line crizotinib versus chemotherapy in ALK-positive lung cancer. N Engl J Med. 2014;371:2167–77. Erratum in: N Engl J Med. 2015;373:1582. [DOI] [PubMed]

Camidge DR, Kim HR, Ahn MJ, Yang JCH, Han JY, Hochmair 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;38:3592–603. [DOI] [PubMed] [PMC]

Zhou C, Kim SW, Reungwetwattana T, Zhou J, Zhang Y, He J, et al. Alectinib versus crizotinib in untreated Asian patients with anaplastic lymphoma kinase-positive non-small-cell lung cancer (ALESIA): a randomised phase 3 study. Lancet Respir Med. 2019;7:437–46. [DOI] [PubMed]

Hida T, Nokihara H, Kondo M, Kim YH, Azuma K, Seto T, 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;390:29–39. [DOI] [PubMed]

10.

Shaw AT, Bauer TM, de Marinis F, Felip E, Goto Y, Liu G, et al.; CROWN Trial Investigators. First-line lorlatinib or crizotinib in advanced ALK-positive lung cancer. N Engl J Med. 2020;383:2018–29. [DOI] [PubMed]

11.

Soria JC, Tan DSW, Chiari R, Wu YL, Paz-Ares L, Wolf J, 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;389:917–29. Erratum in: Lancet. 2017;389:908. [DOI] [PubMed]

12.

Peters S, Camidge DR, Shaw AT, Gadgeel S, Ahn JS, Kim DW, et al.; ALEX Trial Investigators. Alectinib versus crizotinib in untreated ALK-positive non-small-cell lung cancer. N Engl J Med. 2017;377:829–38. [DOI] [PubMed]

13.

Horn L, Wang Z, Wu G, Poddubskaya E, Mok T, Reck M, et al. Ensartinib vs crizotinib for patients with anaplastic lymphoma kinase-positive non-small cell lung cancer: a randomized clinical trial. JAMA Oncol. 2021;7:1617–25. [DOI] [PubMed] [PMC]

14.

Ma HC, Liu YH, Ding KL, Liu YF, Zhao WJ, Zhu YJ, 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;21:1278. [DOI] [PubMed] [PMC]

15.

Cruz BD, Barbosa MM, Torres LL, Azevedo PS, Silva VEA, Godman B, et al. Crizotinib versus conventional chemotherapy in first-line treatment for ALK-positive non-small cell lung cancer: a systematic review and meta-analysis. Oncol Ther. 2021;9:505–24. [DOI] [PubMed] [PMC]

16.

Rücker GKU, König J, Efthimiou O, Davies A, Papakonstantinou T, Schwarzer G. Netmeta: network meta-analysis using frequentist methods. R Package Version 2.6-0 [software]. 2022 Nov 4 [cited 2023 May 6]. Available from: https://github.com/guido-s/netmeta

17.

Chuang CH, Chen HL, Chang HM, Tsai YC, Wu KL, Chen IH, et al. Systematic review and network meta-analysis of anaplastic lymphoma kinase (ALK) inhibitors for treatment-naïve ALK-positive lung cancer. Cancers (Basel). 2021;13:1966. [DOI] [PubMed] [PMC]

18.

Elliott J, Bai Z, Hsieh SC, Kelly SE, Chen L, Skidmore B, et al. ALK inhibitors for non-small cell lung cancer: a systematic review and network meta-analysis. PLoS One. 2020;15:e0229179. [DOI] [PubMed] [PMC]

19.

Wang L, Sheng Z, Zhang J, Song J, Teng L, Liu L, et al. Comparison of lorlatinib, alectinib and brigatinib in ALK inhibitor-naive/untreated ALK-positive advanced non-small-cell lung cancer: a systematic review and network meta-analysis. J Chemother. 2022;34:87–96. [DOI] [PubMed]

20.

Wu KL, Chen HL, Tsai YM, Lee TH, Chang HM, Tsai YC, et al. First-line anaplastic lymphoma kinase (ALK) inhibitors for ALK-positive lung cancer in Asian populations: systematic review and network meta-analysis. J Clin Med. 2021;10:4376. [DOI] [PubMed] [PMC]

21.

Xia B, Nagasaka M, Zhu VW, Ou SI, Soo RA. How to select the best upfront therapy for metastatic disease? Focus on ALK-rearranged non-small cell lung cancer (NSCLC). Transl Lung Cancer Res. 2020;9:2521–34. [DOI] [PubMed] [PMC]

22.

Mok T, Camidge DR, Gadgeel SM, Rosell R, Dziadziuszko R, Kim DW, et al. Updated overall survival and final progression-free survival data for patients with treatment-naive advanced ALK-positive non-small-cell lung cancer in the ALEX study. Ann Oncol. 2020;31:1056–64. [DOI] [PubMed]

23.

Solomon BJ, Bauer TM, Ignatius Ou SH, Liu G, Hayashi H, Bearz A, et al. Post hoc analysis of lorlatinib intracranial efficacy and safety in patients with ALK-positive advanced non–small-cell lung cancer from the phase III CROWN study. J Clin Oncol. 2022;40:3593–602. [DOI] [PubMed] [PMC]

24.

Bauer TM, Felip E, Solomon BJ, Thurm H, Peltz G, Chioda MD, et al. Clinical management of adverse events associated with lorlatinib. Oncologist. 2019;24:1103–10. [DOI] [PubMed] [PMC]

25.

Yoda S, Lin JJ, Lawrence MS, Burke BJ, Friboulet L, Langenbucher A, et al. Sequential ALK inhibitors can select for lorlatinib-resistant compound ALK mutations in ALK-positive lung cancer. Cancer Discov. 2018;8:714–29. [DOI] [PubMed] [PMC]

26.

Britschgi C, Addeo A, Rechsteiner M, Delaloye R, Früh M, Metro G, et al. Real-world treatment patterns and survival outcome in advanced anaplastic lymphoma kinase (ALK) rearranged non-small-cell lung cancer patients. Front Oncol. 2020;10:1299. [DOI] [PubMed] [PMC]

27.

Cranmer H, Kearns I, Young M, Humphries MJ, Trueman D. The cost-effectiveness of brigatinib in adult patients with ALK inhibitor-naive ALK-positive non-small cell lung cancer from a US perspective. J Manag Care Spec Pharm. 2022;28:970–9. [DOI] [PubMed] [PMC]

28.

Cooper AJ, Sequist LV, Lin JJ. Third-generation EGFR and ALK inhibitors: mechanisms of resistance and management. Nat Rev Clin Oncol. 2022;19:499–514. Erratum in: Nat Rev Clin Oncol. 2022;19:744. [DOI] [PubMed] [PMC]

29.

Schmid S, Cheng S, Chotai S, Garcia M, Zhan L, Hueniken K, et al. Real-world treatment sequencing, toxicities, health utilities, and survival outcomes in patients with advanced ALK-rearranged non-small-cell lung cancer. Clin Lung Cancer. 2023;24:40–50. [DOI] [PubMed]

30.

Shaw AT, Solomon BJ, Besse B, Bauer TM, Lin CC, Soo RA, et al. ALK resistance mutations and efficacy of lorlatinib in advanced anaplastic lymphoma kinase-positive non-small-cell lung cancer. J Clin Oncol. 2019;37:1370–9. [DOI] [PubMed] [PMC]

31.

Raphael A, Onn A, Holtzman L, Dudnik J, Urban D, Kian W, et al. The impact of comprehensive genomic profiling (CGP) on the decision-making process in the treatment of ALK-rearranged advanced non-small cell lung cancer (aNSCLC) after failure of 2^nd/3^rd-generation ALK tyrosine kinase inhibitors (TKIs). Front Oncol. 2022;12:874712. [DOI] [PubMed] [PMC]