Comparative analysis of alectinib and brigatinib in real-world treatment of advanced NSCLC with ALK rearrangements

Kyuhwan Kim; Kyu Yean Kim; Hye Seon Kang; Ah Young Shin; Sung Kyoung Kim; Chan Kwon Park; Sang Haak Lee; Seung Joon Kim; Jeong Uk Lim; Chang Dong Yeo

doi:10.1177/17588359251316200

Comparative analysis of alectinib and brigatinib in real-world treatment of advanced NSCLC with ALK rearrangements

Ther Adv Med Oncol. 2025 Feb 7:17:17588359251316200. doi: 10.1177/17588359251316200. eCollection 2025.

Authors

Kyuhwan Kim^{1

2}, Kyu Yean Kim³, Hye Seon Kang⁴, Ah Young Shin⁵, Sung Kyoung Kim⁶, Chan Kwon Park⁷, Sang Haak Lee⁸, Seung Joon Kim^{1

9}, Jeong Uk Lim¹⁰, Chang Dong Yeo¹¹

Affiliations

¹ Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
² Department of Internal Medicine, Armed Forces Goyang Hospital, Goyang, Republic of Korea.
³ Division of Pulmonary, Critical Care Medicine, Department of Internal Medicine, Uijeongbu St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Uijeongbu-si, Republic of Korea.
⁴ Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Bucheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Bucheon-si, Republic of Korea.
⁵ Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Incheon, Republic of Korea.
⁶ Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, St. Vincent's Hospital, College of Medicine, The Catholic University of Korea, Suwon-si, Republic of Korea.
⁷ Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Internal Medicine, Yeouido St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
⁸ Division of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, Eunpyeong St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
⁹ Postech-Catholic Biomedical Engineering Institute, Songeui Multiplex Hall, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
¹⁰ Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Yeouido St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 10, 63-ro, Yeongdeungpo-gu, Seoul 07345, Republic of Korea.
¹¹ Division of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, Eunpyeong St Mary's Hospital, College of Medicine, The Catholic University of Korea, 1021, Tongil-ro, Eunpyeong-gu, Seoul 03312, Republic of Korea.

Abstract

Background and objectives: This study aimed to compare the efficacy of the second-generation anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) alectinib and brigatinib in the treatment of advanced non-small-cell lung cancer (NSCLC) with ALK rearrangements based on real-world data.

Design and methods: We conducted a multicenter retrospective study using the Clinical Data Warehouse from seven university hospitals affiliated with the Catholic Medical Center. Patients diagnosed with ALK-positive advanced NSCLC and treated with alectinib or brigatinib were included. Key outcomes such as time to discontinuation (TTD), duration of response (DOR), overall survival (OS), and objective response rate (ORR) were analyzed.

Results: A total of 143 patients were included (107 treated with alectinib, 36 with brigatinib). Alectinib was more frequently used as a first-line treatment (71% vs 44.4% for brigatinib, p = 0.008). Prior crizotinib treatment was more frequent in the brigatinib group (52.8% vs 22.4% for alectinib, p < 0.001). The best ORR was similar between the groups (84.1% for alectinib vs 83.3% for brigatinib, p = 0.518). The median TTD was 57.8 months (95% confidence interval (CI): 29.0-86.7) for alectinib and 39.6 months (95% CI: 21.7-57.4) for brigatinib (p = 0.462). No significant differences were observed in intracranial TTD, intracranial DOR, or OS between the groups. Prior crizotinib treatment significantly shortened TTD for second-generation TKIs (p = 0.025), but the overall TKI treatment duration did not show a significant difference between patients who received frontline second-generation ALK TKIs and those who received second-generation ALK TKIs sequentially after crizotinib.

Conclusion: Alectinib and brigatinib demonstrated comparable efficacy in ALK-positive advanced NSCLC. Undergoing crizotinib followed by a second-generation TKI was not significantly different from initiating a second-generation TKI without prior crizotinib in terms of outcomes.

Keywords: alectinib; anaplastic lymphoma kinase; brigatinib; carcinoma; non-small-cell lung.

Plain language summary

A real-world comparison of Alectinib and Brigatinib for treating advanced lung cancer This study compares two medications, alectinib and brigatinib, used to treat advanced non-small cell lung cancer (NSCLC) in patients with specific genetic changes called ALK rearrangements. A total of 143 patients were included in the study. Of these, 107 were treated with alectinib and 36 with brigatinib. The results showed that both alectinib and brigatinib had similar effects. There was no significant difference in the overall response to treatment or survival rates between the two drugs. However, the study found that patients who had previously been treated with crizotinib before switching to one of these drugs had shorter treatment durations, but when whole duration of crizotinib followed by alectinib/brigatinib was counted, no significant difference was seen.