Successful application of lorlatinib in a 23-year-old patient with anaplastic lymphoma kinase (ALK)-positive lung cancer and multiple brain metastases - Case Report

Sep 21, 2026

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Background: Anaplastic lymphoma kinase (ALK)-positive lung cancer often responds better to ALK inhibitors, yet resistance to ALK-targeted therapy and ongoing control of central nervous system (CNS) metastases remain major challenges. Case: A 23-year-old man developed multiple brain metastases during alectinib treatment for ALK-positive lung cancer. After lorlatinib initiation, brain metastases disappeared and complete response persisted. Conclusion: Lorlatinib may serve as a first, second, or later-line option for patients with multiple brain metastases following prior ALK inhibitors, supported by good CNS penetration, pending further validation.

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DOI: 10.1002/cnr2.1981 CASE REPORT Successful application of lorlatinib in a 23-year-old patient with anaplastic lymphoma kinase (ALK)-positive lung cancer and multiple brain metastases Yosuke Murakami 1 | Yosuke Kawashima 1 | Shinji Chiba 2 | Shuichiro Hara 1 | Yusuke Yamazaki 1 | Tsuyoshi Doman 1 | Shin Saito 1 | Tetsuo Odaka 1 | Takahiro Ogasawara 1 | Hisashi Shimizu 1 | Jun Sugisaka 1 | Tomoiki Aiba 1 | Yukihiro Toi 1 | Shinsuke Yamanda 1 | Yuichiro Kimura 1 | Shunichi Sugawara 1 1Department of Pulmonary Medicine, Sendai Kousei Hospital, Miyagi, Japan 2Department of Pulmonary Medicine, Iwate Prefectural Central Hospital, Iwate, Japan Correspondence Yosuke Kawashima, Department of Pulmonary Medicine, Sendai Kousei Hospital, Address: 4-15 Hirosemachi, Aoba-ku, Sendai 980-0873, Japan. [Email:](Email: yousukekawashima3@yahoo.co.jp)[ yousukekawashima3@yahoo.co.jp](Email: yousukekawashima3@yahoo.co.jp) Abstract Background: Anaplastic lymphoma kinase (ALK)-positive lung cancer has a better long-term prognosis with ALK-inhibitor than other lung cancers. However, resistance to ALK-inhibitors and the control of metastases in the central nervous system (CNS) remain to be a challenge in the management of ALK-positive lung cancer. Case: We present the case of a 23-year-old man who developed multiple brain metastases while receiving alectinib treatment for ALK-positive lung cancer. After 3 months of lorlatinib initiation, brain metastases disappeared, and complete response (CR) was maintained. Conclusion: While lorlatinib can be used as first line therapy, this drug may be considered as second line or later option for patients with multiple brain metastases if the patient has already been treated with other ALK-inhibitors since lorlatinib is thought to have good CNS penetration. This treatment option should be verified by further research. KEYWOR DS anaplastic lymphoma kinase (ALK)-positive lung cancer, central nervous system (CNS) metastasis, second-line treatment 1 | INTRODUCTION Anaplastic lymphoma kinase (ALK) is a cancer driver gene mutation found in about 3%–5% of lung cancers.1–3 One of the characteristics of ALK-positive lung cancer is that it tends to be more common in younger people than other lung cancers, especially the patient with EML-4 mutated ALK positive lung cancer is reported to be much younger.4,5 In the treatment of ALK-positive lung cancer, the choice of ALK-tyrosin kinase inhibitor (TKI) demonstrates a favorable effect though the majority of cases fall into the acquisition of resistance to the ALK-TKI. Moreover, it is reported that ALK-positive lung cancer patients tend to relapse with central nervous system (CNS) metastasis.6 Lorlatinib is a third-generation ALK-TKI with favorable CNS penetration and it is considered as an option in the treatment of ALKpositive lung cancer with CNS metastasis.7 There is a phase II study for lorlatinib in patients with CNS-only progression on secondgeneration ALK–inhibitors.8 In the study, 15 of 23 (65%) patients had This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. © 2024 The Authors. Cancer Reports published by Wiley Periodicals LLC. Cancer Reports. 2024;7:e1981 . [https://doi.org/10.1002/cnr2.1981](https://doi.org/10.1002/cnr2.1981) [wileyonlinelibrary.com/journal/cnr2](wileyonlinelibrary.com/journal/cnr2) 1 of 5 FIGURE 1 Initial computed tomography (CT) scan showing pericardial effusion and multiple granular shadows and consolidations in both lungs with no evidence of central nervous system metastasis. irradiated CNS metastases, with a median of 20.2 months between radiation and lorlatinib. Conversely, there are limited data about the efficacy of lorlatinib against radiation naïve patients due to the data from a small number of cases. Here we report a case wherein lorlatinib demo

FAQs

Why is managing CNS metastases challenging in ALK-positive lung cancer?

Long-term prognosis can be better with ALK inhibitors, but resistance to ALK inhibitors and the control of metastases in the central nervous system (CNS) remain difficult.

What treatment sequence was used in the presented case?

The patient received alectinib as first-line therapy, developed multiple brain metastases after about 8 months, and then started lorlatinib as second-line therapy.

What was the observed response after starting lorlatinib?

Within 12 days of lorlatinib initiation, contrast-enhanced MRI showed that multiple brain metastases generally decreased in size and the patient’s symptoms dramatically improved; complete response was maintained after about 3 months.

Sep 21, 2026

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