Efficacy and safety analysis of lorlatinib for ALK-positive advanced NSCLC: a multicentre real-world study in China
Abstract Background Lorlatinib, a third-generation Anaplastic lymphoma kinase (ALK)-tyrosine kinase inhibitors (TKI), has demonstrated excellent curative effect in clinical studies to overcome mutations resistant to first- and second-generation ALK-TKIs. It also has improved blood-brain barrier cros...
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| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
BMC
2025-07-01
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| Series: | BMC Cancer |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12885-025-14631-w |
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| Summary: | Abstract Background Lorlatinib, a third-generation Anaplastic lymphoma kinase (ALK)-tyrosine kinase inhibitors (TKI), has demonstrated excellent curative effect in clinical studies to overcome mutations resistant to first- and second-generation ALK-TKIs. It also has improved blood-brain barrier crossing and reduced brain metastases. Methods 44 patients were selected who received Lorlatinib as initial treatment for first-diagnosis ALK-positive non-small-cell lung cancer (NSCLC) or who received Lorlatinib as a back-line treatment after developing resistance with first- and second-generation ALK-TKIs. The primary study endpoints are objective response rate (ORR) and disease control rate (DCR). Results For the 44 patients, the overall ORR[95% confidence intervals (CI)]was 59% (95% CI: 51–69), the DCR was 93% (95% CI: 36–56). In the first-line treatment group(n = 15), lorlatinib showned an ORR 93% (95% CI: 52–81), and the DCR was 100% (95% CI: 47–78). Additionally, 29 patients who received sequential Lorlatinib after progression on at least one first- or second-generation ALK-TKI showned an ORR of 41% (95% CI: 41–63) and a DCR of 90% (95% CI: 20–40). Lorlatinib demonstrated strong intracranial efficacay, with an overall intracranial objective response rate (IC-ORR) of 74% (95% CI: 67–92) and an intracranial disease control rate (IC-DCR) of 96% (95% CI: 53–81) in 23 patients with brain metastase. Among them, the IC-ORR and IC-DCR of 7 patients who received Lorlatinib as first-line therapy were both 100% (95% CI: 89–103). For 16 patients who had received at least one ALK-TKI, the IC-ORR with Lorlatinib was 63% (95% CI: 51–90), and the IC-DCR was 94% (95% CI: 27–70). 44 patients treated with Lorlatinib, all at a starting dose of 100 mg/day, 77% experienced adverse events, with the most common associated adverse event being hyperlipidaemia, However the overall grading was mild to moderate, with only one case of a reduction in dosage to 75 mg. Conclusions This real-world evidence demonstrates that Lorlatinib exhibits significant clinical efficacy and intracranial anti-tumor activity in the treatment of ALK + NSCLC patients, whether in first-line or post-first-line treatment, while being well tolerated. |
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| ISSN: | 1471-2407 |